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“Repeat A Little:” Time And Freedom In Deleuze’S Difference And Repetition, Mine Sak

Electronic Theses and Dissertations

In this dissertation, I examine Gilles Deleuze’s philosophy of time as presented in Difference and Repetition and use it to construct a concept of freedom, which is notably absent in his work. I argue that Deleuze’s exposition of the three syntheses of time provides significant insights for exploring the ontological possibility and structure of freedom. Through an analysis of his theory of the three syntheses of time, I investigate the meanings of agency, destiny, and choice within Deleuze's framework. I demonstrate that free choice necessitates both involuntary and creative action. Given the apparent tension between freedom and involuntariness, I explore …

Advancing Continuous Manufacturing: The Role Of Process Analytical Technology In Process Development, Samuel R. Henson

Electronic Theses and Dissertations

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance …

Hidden Markov Model For Identifying Local Variants In Human Genomes Using Simulated Data, Scott Mccallum

Electronic Theses and Dissertations

Identifying adaptive mutations in genetic data is challenging due to the low frequency of occurrence of such events, and because signatures of selection are intertwined with the footprints of various other evolutionary forces that shape our genomes. Even when a larger region appears to be under selection, genomic sites that are linked to adaptive mutations have similar statistical signals, and thus can obfuscate the identification of the actual adaptive mutation. The new method described here uses a Hidden Markov Model that allows for classification of neutral, linked, and sweep (adaptive mutation) genomic sites. This model is general and can be …

Method Development Of [3 + 2] Cycloadditions Using Tertiary Amine N-Oxides And Efforts Towards The First Total Synthesis Of Chrysosporazine D, Alexander Cocolas

Electronic Theses and Dissertations

Nitrogen-containing heterocycles are ubiquitous in bioactive molecules, pharmaceutical drugs, and natural products. For this reason, finding new and efficient ways to make such compounds remains a high priority for the organic and medicinal community. Our current endeavors build upon previously established work by our group, where we generated 1,2-diamines by coupling commercially available aldehydes with trimethylamine N-oxide (TMAO) in two steps. This route proved to be effective in generating 20+ novel 1,2-diamines and imidazolidines with a demonstrated ability to undergo transformations. Using this chemistry, we have developed a diastereoselective synthesis of 50+ novel 7-azanorbornanes using tertiary amine N-oxides …

Ethical Considerations In The Diagnosis And Treatment Of Autism Spectrum Disorder, Ferdinand Okafor

Electronic Theses and Dissertations

This dissertation is an ethical response to the ethical issues in the assessment, diagnosis, and treatment of autism. The problems that underlie the discussion are misconception about autism and Autistics. The misconception about autism and Autistics lead to misinterpretation of the neurological functioning, cognition, and the behaviors of Autistics. Consequently, it influences the approach and model of care in the assessment, diagnosis, and treatment of autism. Currently, the analytic approach and biomedical model of disease are applied in the assessment, diagnosis, and treatment of autism. The motive of the analytic approach and biomedical care is to cure autism. The consequence …

Rna Structural-Dynamical Hierarchy: Sars-Cov, Sars-Cov-2, And Delta/Omicron Variant S2m Monomers, Kissing Complexes, And Extended Duplexes, Adam Kensinger

Electronic Theses and Dissertations

The power and promise of ribonucleic acid (RNA) molecules are only beginning to be realized in living organisms and pharmaceutical intervention. Specifically, defining the chemical physics of RNA’s heterogenous structural ensemble and dynamics, which has experienced expansive growth over the last few years, is central to a complete understanding, yet continues to be a significant challenge. A 41-nucleotide hairpin called the stem-loop II motif (s2m), present in the viral genomes of severe acute respiratory syndrome (SARS), SARS-coronavirus-2 (SARS-CoV-2), and the Delta and Omicron variants responsible for the COVID-19 pandemic, is a potential antiviral target due to its high sequence conservation …

Efficient Development Of Density-Insensitive Near-Infrared Methods For In-Line Drug Content Monitoring In Continuous Powder Streams, Natasha L. Velez-Silva

Electronic Theses and Dissertations

A well-defined action plan to respond effectively to sudden changes in product demand is critical for preventing drug shortages within the pharmaceutical industry. An effective way to increase the output of a continuous manufacturing (CM) process is through flow rate adjustments. However, robust analytical methods must be in place to ensure consistent analytical performance across varying flow rates. Existing approaches for mitigating the physical effects of flow rate on Near-Infrared (NIR) measurements are often burdensome. Thus, efficient robust modeling strategies that reduce the current calibration burden and ensure model insensitivity to the physical variations in CM systems are needed. In …

Muslim Spirituality As A Foundation In Bioethics For Patient Encounters In Health Care, Sara Rahman

Electronic Theses and Dissertations

Spirituality plays a major role in decision making for individuals with faith-based values. There is often hesitation to discuss the role of faith in healthcare as a core value and coping mechanism. The growing cultural diversity amongst patients and physicians has increased the need to understand eastern religious principles and incorporate them into bioethical guidance. Even as the 2nd largest religion in the world, Islam has not been sufficiently integrated into religious bioethics in western medicine. Muslim populations of patients and physicians are growing, increasing the need for better understanding of how Islamic principles impact healthcare delivery. Although Islamic law …

Design, Synthesis, And Characterization Of Multi-Targeting Pyrrolopyrimidine Antifolates As Potential Single Agent Chemotherapeutic Entities, Tejashree Magdum

Electronic Theses and Dissertations

In cancer chemotherapy, the currently marketed antifolates have two major disadvantages: dose-limiting toxicities to normal tissues and susceptibility to drug resistance. These are due to their major transport by the ubiquitously expressed transporter and mutagenesis in enzymes present in cancer cells. This thesis describes an introduction, background, and research progress in antimetabolites-antifolates designed to multi-target (a) one-carbon metabolism and de novo nucleotide synthesis pathway and (b) target overexpressed transporter in cancer cells for selective tumor-targeting.

Cancer cells transport folate through three transporters: ubiquitously expressed reduced folate carrier (RFC), limitedly expressed proton-coupled folate transporter (PCFT), and folate receptors (FRs). The research …

Assembly Of Ppsu-Oligomers, Mariam Nesterov

Student Theses and Dissertations

The development of nanostructures for delivering multiple proteins to targeted antibodies has become a promising avenue in biotechnology, driven by advancements in synthetic polymers like poly(propylene sulfone), PPSU. However, the PPSU polymer faces a major limitation - its high insolubility. To address this challenge, this study investigates whether PPSU oligomers can enhance both the solubility and stability of lysozyme, a model protein that is cost-effective and widely accessible. Using dimer, trimer, tetramer, and hexamer configurations, we analyzed the interactions between PPSU oligomer and lysozyme under varying conditions. Our results show that the dimer and trimer are water soluble (no aggregate …

Organ-On-A-Chip Platforms For Drug Development, Cellular Toxicity Assessment, And Disease Modelling, Muhammad Maaz Khurram, Göktürk Ci̇nel, Özlem Yeşi̇l Çeli̇ktaş, Erdal Bedi̇r

Turkish Journal of Biology

Organ-on-a-chips (OoCs) or microphysiological platforms are biomimetic systems engineered to mimic organ structures onto microfluidic devices for biomedical research. These microdevices can mimic biological environments that enable cell-cell interactions at a small scale by mimicking 3D in vivo microenvironments outside the body. Thus far, numerous single and multiple OoCs that recapitulate organs have been developed, and they have emerged as forerunners for drug efficacy and cytotoxicity testing. This review explores OoC platforms to portray their versatility in investigating drug safety, efficacy, and toxicity. We also reflect upon the potential of OoCs to effectively demonstrate disease models for probable novel therapeutics, …

Mechanistic Insights Into Cardiac Regeneration And Protection Through Meis Inhibition, Aynura Mammadova, Gali̇p Servet Aslan, Li Mo, Qifang Wu, Sebastian Clauss, Fati̇h Kocabaş

Turkish Journal of Biology

MEIS1, a member of the TALE-type homeobox gene family, has emerged as a pivotal regulator of cardiomyocyte cell cycle arrest and represents a promising therapeutic target. Our study reveals that inhibition of MEIS1 using two novel small molecules, MEISi-1 and MEISi-2, significantly enhances neonatal cardiomyocyte proliferation and cytokinesis. Specifically, MEISi-1 and MEISi-2 increased the proportion of proliferating cardiomyocytes (Ph3+TnnT cells) upto 4.5 fold and the percentage of cytokinetic cardiomyocytes (AuroraB+TnnT cells) by 2 fold, compared to untreated controls. MEIS1 inhibition resulted in a notable downregulation of MEIS1 target genes and cyclin-dependent kinase inhibitors, demonstrating its effect on key regulatory pathways. …

Chelidonic Acid Abrogates Oxidative Stress And Memory Dysfunction In Experimental Aging Rats, Feri̇de Ni̇hal Si̇nan, Emel Serdaroğlu Kaşikçi, Burcu Çevreli̇

Turkish Journal of Biology

Background/aim: In an aging model established in male Wistar albino rats via the administration of D-galactose (D-gal), the aim of this study was to examine the effects of chelidonic acid on cognitive functioning and the levels of glutathione (GSH), malondialdehyde (MDA), Total antioxidant status (TAS), and brain-derived neurotrophic factor (BDNF).Materials and methods: Thirty-two Wistar albino (three month old) male rats (n = 8) were used. Group 1: Control (C), Group 2: Chelidonic acid (CA) (2 mg/kg oral gavage), Group 3: D-galactose (D-gal) (150 mg/kg, s.c.), Group 4: D-gal (150 mg/kg) + CA (2 mg/kg) (DC). Following an overnight fast, the …

Characterization Of Tfiie-Regulated Genes By Transcriptome Analysis, Serdar Baysal

Turkish Journal of Biology

Previous studies on GTF2E showed that it has association with certain group of diseases such as colon cancer and trichothiodystrophy but what is the global effect of GTF2E on cellular processes is not widely characterized. In this regard, this study aimed to investigate and characterize the affect of GTF2E on transcription level of genes and identify the cellular processes and diseases associated with GTF2E. The HCT116 cell line was used in the study and transfected at 30 nM concentration with siGTF2E1 or non-target negative siRNA. After 72 hours, cells were harvested and prepared for further analysis. Whole transcriptome analysis was …

Copyright And Research In Latin America: Law, Courts, And Perceptions, Mariana G. Valente, Alice P. Lana, André P. Houang

Joint PIJIP/TLS Research Paper Series

Research on the intersection of copyright law, research activities, and innovation in Latin America reveals significant deficiencies in the legal framework and public discourse surrounding copyright limitations and exceptions (L&Es) for research purposes. The problem is more visible with modern data assembling and analyzing techniques, such as through artificial intelligence (AI) systems. This study highlights the scarcity of explicit provisions for research-related exceptions in the region by examining copyright legislation, case law, and stakeholder perspectives in six Latin American countries. Despite indications that judicial interpretation is expanding the scope of L&Es, particularly in Brazil, awareness of legal nuances remains low …

Design And Investigation Of Small Molecule Drugs For Potential Treatment Of Cns Disorders, Flaviviral Infections, And Cancers, Viktoriya Mashinson

Theses & Dissertations

Chapter 1 discusses the development of antagonists against the dopamine 4 receptor (D4R) that is expressed in the motor, associative, and limbic subdivisions of the basal ganglia network and is involved in Parkinson’s disease (PD). Levodopa is the firstline drug for the management of PD symptoms but its long-term use often leads to development of levodopa-induced dyskinesia (LID). D4R antagonists have been shown to decrease the abnormal involuntary movement scores in mouse models of LID. Chapter 1 outlines the development and optimization of selective D4R antagonists for potential treatment of LID. During the investigation of our D4R antagonists we discovered …

Characterizing The Francisella Tularensis Universal Stress Protein, Benjamin Girardo

Theses & Dissertations

Francisella tularensis is an extremely virulent pathogen responsible for the zoonotic disease tularemia. F. tularensis employs various defense mechanisms to survive and persist under diverse environmental and host-induced stress conditions. Despite its significance, the full spectrum of stress factors that enable F. tularensis persistence remain inadequately understood. In many bacterial species, universal stress proteins (Usp) play a crucial role in managing adverse conditions. The aim of this study was to elucidate the role of Usp in F. tularensis as a means of clarifying the stress response mechanisms of this pathogen. The F. tularensis Usp is encoded by a single, highly …

Sparkled: Social Programming In Kids Affects Risk Of Latent Endothelial Disease, Rebecca Drakowski

Theses & Dissertations

Background: Social Health Programming (SHP) is a holistic intervention that can empower communities to address modifiable risk factors for poor cardiovascular health, including suboptimal nutrition or psychosocial stressors. SHP participation has been shown to increase dietary intake of fruits and vegetables, decrease perceived stress, and improve cardiovascular endurance. However, it is unknown how SHP participation during adolescence affects carotenoid serum levels, hair cortisol concentrations (biological marker of chronic stress), or vascular reactivity index (VRI; measure of subclinical cardiovascular health).

Methods: Adolescent girls and young adult women (12–29-year-old) were enrolled in this observational cohort study. Serum, hair, and saliva samples were …

Development Of A Streptococcus Mutans Biofilm Model On A Typodont Platform To Investigate Its Dynamics In Orthodontics, Hibah Chughtai

Theses & Dissertations

Introduction: Biofilm formation plays a significant role in dental health, resulting in plaque accumulation, which can lead to caries and oral diseases. Streptococcus mutans (S. mutans) is a key bacterium involved in this process. The goal of this study was to establish a protocol for the development of an S. mutans biofilm on dental typodont teeth to analyze the effects of orthodontic brackets on biofilm formation. Understanding these dynamics is critical for developing strategies to mitigate biofilm accumulation during orthodontic treatment. Methods: S. mutans biofilms were cultivated under three conditions: 96-well tissue culture plates, S. mutans inoculated non-bracketed …

Ccr5-Ligand Decorated Rilpivirine Lipid-Based Nanoparticles For Sustained Antiretroviral Responses, Milankumar Patel

Theses & Dissertations

Antiretroviral therapy (ART) is the standard remedy to improve the health-related quality of life of people living with human immunodeficiency virus (HIV). However, limited access to the viral reservoir has significantly hindered its effectiveness in fully eradicating HIV. Therefore, to improve HIV therapy, here we propose a C-C chemokine receptor type 5 (CCR5)-targeted theranostic lipid Based Nanoparticles (LBNPs) to noninvasively track and specifically deliver the antiretroviral drugs (ARVs) to the viral reservoir. A multi-modular radioactive nanoprobe was synthesized and co-encapsulated with rilpivirine (RPV, an ARV) into the LBNP to achieve a theranostic LBNP that can be tracked by positron emission …

Synthetic Studies On Ship Activators And New Oxidative Methods Utilizing Ddq And Hypervalent Iodine Catalysts, Christos Nixarlidis

Dissertations - ALL

One important cell signaling pathway is the PI3K pathway because it influences many key cellular functions such as proliferation and apoptosis. Among the enzymes that are involved in this pathway, the SH2-containing inositol-5’-phosphatase (SHIP) plays an important role by maintaining the balance of PI(3,4,5)P3 and PI(3,4)P2. SHIP activation promotes a higher rate of hydrolysis of PI(3,4,5)P3 and thus reduces the downstream activation of AKT, which influences many cell processes. Activation of SHIP using small molecules may be useful for certain diseases such as inflammatory disorders and some types of cancer. The synthesis and evaluation of a new class of sulfonamide …

Noise-Enhanced Network Science, Reyhaneh Abdolazimi

Dissertations - ALL

Graphs are a versatile and powerful data structure used to model complex relationships in diverse domains such as social networks, biological systems, and transportation networks. In graphs, entities are represented by nodes, and interactions or relationships between them are represented by edges. For example, in the World Wide Web, web pages are considered vertices, and if there is a link from one page to another page on the web, there will be a directed edge between those pages in its graph data structure. These structures allow us to analyze and solve important problems like community detection (identifying closely related clusters …

Modulating Liquid-Liquid Phase Separation Of Intrinsically Disordered Proteins Through Lipidation, Zhe Zhang

Dissertations - ALL

Liquid-liquid phase separation (LLPS) is a fascinating biological phenomenon that enables cells to form membraneless organelles, creating specialized compartments for orchestrating complex biochemical reactions. While significant progress has been made in deciphering the sequence determinants underlying phase separation, precisely modulating these features remains a challenge. Inspired by biology, post-translational modifications (PTMs) offer a promising approach to modulate the protein condensates formation and their properties in real-time, without altering the sequences. Despite the identification of over 300 types of PTMs, most research has predominantly focused on charge-altering modifications. The effects of non-charged PTMs, such as lipidation, on LLPS remain poorly understood. …

Role Of Emotional Intelligence In Leadership, Sabrena Craft

M.S. in Leadership

No abstract provided.

Biobehavioral Correlates Of Multidimensional Fatigue In Men With Prostate Cancer, Kristin Dickinson

Theses & Dissertations

The purpose of this thesis project was to 1) examine trajectories of multidimensional cancer-related fatigue (CRF) in men with prostate cancer during and after radiation treatment completion, and 2) identify biobehavioral correlates (demographic, clinical, co-occurring symptoms, and biologic [inflammatory cytokines]) for the different CRF dimensions.

Data for this secondary analysis were obtained from a descriptive, longitudinal IRB-approved study investigating men with non-metastatic prostate cancer receiving radiation therapy (RT). Data were obtained from 68 participant medical records, self-report questionnaires, and blood samples. Data were collected at: baseline (T1), completion of RT (T2), 6 months (T3) and 2 years (T4) after completion …

The Plasmodium Falciparum Ncr1 Transporter Is An Antimalarial Target That Exports Cholesterol From The Parasite's Plasma Membrane, Zhemin Zhang, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,

P85Α Degradation Mediated By Ubiquitin E3 Ligase Fbxo21 Offers Therapeutic Potential In Leukemia, Kasidy K. Weber

Theses & Dissertations

Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by the clonal expansion of myeloid blasts in the bone marrow. Despite significant therapeutic advances over the years, the prognosis for AML patients remains dismal, with high relapse rates and poor overall survival. The ubiquitin-proteasome system (UPS) plays a critical role in maintaining cellular homeostasis by regulating the degradation of proteins involved in essential processes such as cell cycle control, DNA repair, apoptosis, and various signaling pathways. Given this vital function, targeting ubiquitin E3 ligases within the UPS presents a promising strategy for developing more effective and targeted therapies …

A Comprehensive Usability And Economic Analysis Of Heat-Related Wearable Technologies: Applications To Occupational Health, Ryan T. Cannady

Theses & Dissertations

The purpose of this research was to analyze the usability and economic considerations of real-time wearable technologies that are implemented in occupational settings to assess risk of heat stress and heat strain. The study population included current agriculture workers and Department of Energy (DOE), Environmental Management (EM) contractors. We employed a mixed-methods approach to comprehensively analyze the usability and economic considerations of heat-related technologies. Specifically, our approach assessed three distinct aspects the applications of these technologies in occupational settings to comprehensively address our research objective: (1) worker perceptions of heat-related wearable technologies, (2) field-based assessment of these heat-related wearable technologies, …

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …