Digital Commons Network^™

Synthesis And Applications Of Α,Β-Dehydroamino Acid-Containing Peptides, Diego A. Moya

Theses and Dissertations

Yaku’amide A (YA) is a linear anticancer peptide that is rich in bulky dehydroamino acids (ΔAAs) and β-hydroxyamino acids (β-OHAAs). In our recent total synthesis of YA, we featured a one-pot anti dehydration–azide reduction–O→N acyl transfer process for the stereospecific construction of Z- and E- ∆Ile residues. Despite previous total syntheses and our efforts, the synthesis of YA remains lengthy. Via computational studies, we identified two analogue peptides that closely resemble the conformation of YA. The use of simpler and symmetrical bulky ΔAAs such as dehydrovaline (ΔVal) and dehydroethylnorvaline (ΔEnv) as surrogates of ∆Ile, along with azlactone chemistry for their …

Synthesis Of Yaku’Amide A Analogues And Impact Of Dehydroamino Acids On The Structure And Stability Of Incipient 310 Helical Peptides, Daniel Joaquin

Theses and Dissertations

The first project in this dissertation describes the total synthesis of yaku’amide A analogues. Natural product yaku’amide A possesses potent anticancer activity and exhibits a novel mode of action. However, due to its complex asymmetrical isoleucine dehydroamino acids, the synthesis of this polypeptide poses a unique challenge. Despite the efficient synthesis developed in our lab, the total synthesis of this natural product remains lengthy. In order to simplify the overall synthesis, symmetrical dehydroamino acids were incorporated to replace the dehydroisoleucine residues yielding two analogues of yaku’amide A that closely resembles the conformation of the natural product. Biological testing of the …

Computer Vision And Machine Learning Applications In Cellular Images And Clinical Data, Guochang Ye

Theses and Dissertations

With the progressive development of artificial intelligence (AI), automated analysis has been explored for substituting tedious manual methods in cellular image analysis. Additionally, medical information not included in the conventional statistical methods is now being reconsidered with AI-based personalized medicine. The adaptivity and flexibility of AI ensure its efficiency and accuracy. In this work, computer vision and machine learning (ML) methods under the scope of AI are explicitly investigated and applied to cellular images and clinical data for cytological analysis and to provide diagnosis-based assistance/predictions. Firstly, novel computer vision algorithms achieve cell detection and differentiation estimation on phase-contact microscopic images …

Removal Of Arsenic (Iii) And Arsenic (V) From Aqueous Solution Via Common Sunflower Helianthus Annuus By Phytoremediation, Irving A. Vazquez Hurtado

Theses and Dissertations

Phytoremediation provides a cost-effective, non-invasive technique to remove contaminants from the soil and groundwater. Sunflowers are fast growing and have a showed effective at removing various pollutants from soil, including lead and other heavy metals. Health issues related to arsenic are mainly attributed to exposure of arsenite, whereas arsenate is much less toxic. The common sunflower Helianthus annuus was the species used to remove both arsenic (III) and As(V) ions from hydroponics solutions. In the present study sunflower seeds were germinated for a week, placed under the sun for a day and subsequently placed in a nutrient solution to aid …

Biological Sex Differences In The Monodelphis Domestica: Investigating Behavioral Responses In Environmental Enrichment And Conditioned Place Preference Paradigms, Katelynn M. Renteria

Theses and Dissertations

The Monodelphis domestica, commonly known as the grey short-tailed opossum, has become an increasingly frequented animal model for areas of psychological study, including comparative psychology. Despite the growing interest in utilizing the Monodelphis as an animal model, several areas of research remain limited in what has been studied. This includes associative learning and the effects of environmental enrichment on the Monodelphis. This study novelly incorporates the two using environmental enrichment with the conditioned place preference (CPP) paradigm to both diversify associative learning literature and expand existing knowledge on the Monodelphis domestica. The CPP paradigm included interactive objects as environmental …

The Effects Of Ionizing Radiation On Domestic Dogs: Ancestry And Genetic Structure Of Free-Roaming Dog Populations In Chernobyl, Ukraine, Gabriella Jean Spatola

Theses and Dissertations

This thesis is concerned with the effects of ionizing radiation on domestic dogs (Canis lupus familiaris) which were commonly used as laboratory subjects during the era of atomic bomb testing (1950s - 1980s). Early laboratory studies on radiation effects in dogs provided important foundations of knowledge for research that has more recently shifted to natural populations exposed to ionizing radiation from nuclear accidents. A unique group of free-roaming dogs reside in an environment polluted by radioactive contamination deposited during the Chernobyl nuclear disaster of 1986, providing one such opportunity to study the effects of ionizing radiation on dogs …

Microwave-Promoted Iminyl Radical Fragmentations And The Total Synthesis Of Yaku'amide A And Its Simplified Analogues, Concordia Lo

Theses and Dissertations

The first project in this dissertation describes the use of microwave-promoted iminyl radical fragmentations to form functionalized nitriles. Nitrogen-centered radical chemistry is a useful tool to construct valuable C-N bonds commonly found in pharmaceuticals and biologically active molecules. Classically, these reactions require the use of toxic initiators and propagators. Iminyl radical chemistry has been gaining momentum as a means of avoiding these harsh conditions. This project utilizes the fragmentation of cyclic iminyl radicals via irradiation of O-phenyl oxime ethers to produce a synthetically useful nitrile tethered to an alkyl radical in the absence of metal catalysts and redox chemistry. The …

Placing Value On Environmental Literacy: A Case Study Of Biology Faculty Experiences, Ilene Sigrid Eberly

Theses and Dissertations

The purpose of this case study was to explore how contingent biology instructors place value on environmental literacy in their instruction and the instructional strategies used to foster their student's environmental literacy. This study also investigated the contextual experiences of contingent instructors influencing the value they place on environmental literacy. Participants included 11 faculty teaching introductory biology courses from two public universities in the Northeast. Our analysis focused on triangulation of participants semi-structured interviews, instructor-generated artifacts, and field notes from classroom observations, interviews, and artifacts. Findings revealed contingent biology instructors understand the importance of placing value on environmental literacy in …

The Impact Of Using An Online Learning Management System On Student Biology Achievement In A Hispanic Rural High School, Brent J. Burkott

Theses and Dissertations

The purpose for this study was to determine the effect of using online Learning Management Systems with a Blended Learning pedagogy on state assessment achievement of high school biology students with interactions analyzed based on teaching method (Face-to-Face/Blended Learning), course type (Honors/Regular) biological sex (Male/Female), risk factor (At-Risk/Not At-Risk), and socioeconomic status (High/Low). The research questions were: (1) What is the difference in achievement scores between students taught in a Blended Learning environment with a Learning Management System verses a traditional Face-to-Face learning environment, and (2) What differences in achievement exist on the Texas assessment based on teaching method, course …

Spatial Ecology And Stable Isotope Composition Of Cetaceans In The Bohol Sea, Edna Sabater

Theses and Dissertations

Studies on Philippine cetaceans (i.e., whales and dolphins) began in the early 1980s, and have resulted in the location and identification of species in Philippine waters. However, the population estimates of most of the cetacean species are uncertain, which is important in evaluating whether the populations are stable, decreasing, or increasing in relation to potential threats and conservation measures. I conducted line-transect surveys between 2010 and 2019 in the Bohol Sea, Philippines. A total of 2009.5 km survey efforts were made, which covered an area of 8041 km2 throughout the 5-year survey period. Distance sampling methods estimated the total abundance …

The Impact Of Global Crises On Women: The Case Of Covid-19 In Egypt, Nour A. Dokhan

Theses and Dissertations

Any global crisis is expected to affect every human being, but for women it is always twice as hard. In the case of Covid-19, women are more affected across every domain, from social protection to health, simply because if their gender. This research explores the impact of Covid-19 on women, both economically and socially, with the focus on the case of Egypt. It explores the systematic gender inequalities in the economic, social, and health spheres using cases from previous crises, and how this gender inequality and vulnerability has resulted in much worse consequences of Covid-19 than that of men. The …

Metastable State Photoacids And Ultrasound Responsive Carbon Monoxide Releasing Polymer Micelle, Osamah Zaid Saleh Alghazwat

Theses and Dissertations

This dissertation described my Ph.D. work on the development of a novel metastable state photoacids (mPAH), which can be activated by near infrared light and a reversible mPAH switched by different wavelengths of light. Also, it described the development of a micelle that responded to ultrasound to localized carbon monoxide CO delivery. An introduction of metastable state photoacid is given in Chapter 1. In Chapter 2, described my work on the development of a novel mPAH, which can be activated by near infrared light is an important factor for various biological functions. mPAH was designed and synthesized with a donor-acceptor-donor …

Design And Synthesis Of Polymeric Metastable State Photoacid And Photo Co-Releasing Materials, Adnan Abdallah Muftah Elgattar

Theses and Dissertations

Metastable state photoacids (mPAHs) are molecules that possess a photoinduced metastable state with high acidity and good reversibility. The metastable state lasts long enough to produce a high proton concentration, which can drive various proton transfer processes. MPAHs have been intensively studied in recent years and applied to different chemical, material, biomedical areas. Covalently linking many mPAHs in a polymer allows the generation of a local proton concentration higher than that of the overall system. This dissertation described my PhD work on the synthesis of mPAH polymers using different radical and ring-opening polymerization methods. These polymers can repeatedly produce a …

Herbal Extracts As Neuroprotective Agents In An In-Vitro Model Of Aluminum Neurotoxicity, Nada Ezzelarab

Theses and Dissertations

Background: Aluminum toxicity due to environmental or industrial exposure, medical applications, or from cooking utensils is a serious medical problem. The current study aims to investigate three herbal extracts: pomegranate peel extract, Achillea fragrantissima extract, and papaya fruit extract to combat this neurotoxicity.

Methods: Chemical characterization of the three extracts were evaluated using HPLC MS while their neuroprotective activity was assayed using MTT assay on SHSY5Y cells and nitric oxide levels.

Results: Using HPLC-MS chromatography, we have identified twenty-one compounds in the hydro-alcoholic Achillea fragrantissima, seventeen were determined in the pomegranate peel, eleven were assessed in the Carica papaya …

Molecular Basis Of Xenobiotic Metabolism And Resistance In Tetranychus Urticae, Leily Daneshian

Theses and Dissertations

Invasive pest species are a major cause of crop loss around the world and adversely affect the agricultural industry. We are focusing on Tetranychus urticae (two-spotted spider mite; TSSM), which is a polyphagous pest that targets more than 1100 plant species. The TSSM alone causes a loss of roughly $1.6 billion per year globally due to acaricide resistance. It is developing resistance to most acaricides due to rapid growth and reproduction. Therefore, new acaricides are needed to combat TSSM resistance and infestation [1]. To address this problem, four enzymes of TSSM, intradiol ring cleavage dioxygenases, a glutathione S-transferase, a β …

Exploring Efficacy Of An Anti-Malarial Nanomedicine In Non-Small Cell Lung Cancer Treatment, Vineela Parvathaneni

Theses and Dissertations

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes and formulation parameters so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded …

Development Of Analytical Methods For Analysis Of Glycosaminoglycans And Their Mimetics In Human Plasma, Rawan M. Fayyad

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear, polydisperse polysaccharides consisting of alternating amino sugars and either a uronic acid or galactose residue. They are ubiquitous components of the extracellular matrix and are present on cell surfaces and in basement membranes. GAGs are highly negatively charged as a result of many sulfate and carboxylic acid groups, and are extremely heterogeneous in both their structure and in their physicochemical properties. This complexity in structure is attributed to the alterations in residue types, glycosidic bond linkage, sulfation levels, sulfation positions, and chain lengths during biosynthesis. GAGs interact with a wide number of proteins and modulate various …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Development Of Plant Extract-Based Composite Fibers And Aerogels, Raul C. Barbosa

Theses and Dissertations

The aim of this study is to use the solid templating process of pullulan nanofibers in order to produce biocompatible, biodegradable, and antibacterial aerogels. The developed aerogels were produced using cross-linked pullulan nanofibers, which provide a water-stable structure allowing them to be used as wound dressing material. The morphology, thermal properties, water solubility, and thermal and physical properties of the nanofibers and aerogels were characterized. Furthermore, the antibacterial effect against gram-negative bacteria, Escherichia coli, and the biocompatibility using mouse embryonic fibroblasts (NIH 3T3) were investigated.

The Development Of A New Entry Point Into Enantiomerically Enriched Sulfinyl Derivatives, Jessica Shaw

Theses and Dissertations

Optical probes may be used as reliable tools for detecting and imagining the inside of cells for medical diagnostics. Among available options, the use of thiol probes is of interest as thiols are present in nearly all cells and their levels are tightly regulated, thus any variation is associated with disease. A proper thiol bioimaging probe must have a thiol cleavage group/reactive group and a fluorophore. It is found that novel sulfinate aryl ester (phenoxysulfinate esters) probes selectively cleave thiols at physiological pH and show much promise as effective tools for bioimaging.

In this context, the synthesis of the related …

Biomaterials For Bone Regeneration: Tunable Structural And Mechanical Characteristics, Anwer Mhanawee

Theses and Dissertations

Tissue engineering is a promising alternative treatment for damaged tissues. In bone regeneration, bone graft replacements can be made from different biomaterials (basically ceramic and polymer) and used for different treatment purposes. In the first section of this dissertation, the Compression test results showed that its modulus of elasticity depends on its porosity. Also, we developed a testing method to measure the swelling force of the material during expansion due to liquid absorption. The maximum swelling force was found to be proportional to the material modulus. In the second part, we successfully design, fabricate and characterize a novel expandable bone …

Recombinant Expression Of Preptin Analogs For Alanine Scanning Mutagenesis Of Residues 27-29, Tehgan N. Anguilm

Theses and Dissertations

The novel peptide preptin consists of 34 amino acid residues corresponding to Asp⁶⁹-Leu¹⁰² of proinsulin-like growth factor E-peptide. Preptin has been isolated from pancreatic beta cells, and it has been found to exhibit both metabolic and mitogenic activities. This makes preptin an attractive candidate to treat insulin-independent diabetes and osteoporosis. Alanine scanning mutagenesis was utilized to substitute an alanine for residues Trp²⁷, Arg²⁸, and Gln²⁹ of preptin in order to ultimately study the structure-activity relationship of these residues to preptin’s metabolic activity.

Oil/Water Nanoemulsion Biodistribution In Mice Upon Intravenous Administration, Jiayi Chen

Theses and Dissertations

The present study aimed to explore the biodistribution of O/W nanoemulsions (NE) upon intravenous administration. Three NEs were prepared with distinctive droplet sizes: SE (29 ± 1 nm), ME (214 ± 2 nm) and LE (883 ± 16 nm) without overlapping of the size distribution. Kolliphor® HS15 was used as the only surfactant for these three NEs, so that their droplets had similar surface structure. The NEs droplet size was stable under room temperature for minimum 3 days in phosphate buffer saline (PBS) and in mice plasma in vitro for 4-hour at 37°C. A lipophilic fluorescent dye, 1, 1’-dioctadecyl-3, 3, …

Heparan Sulfate. A Ligand For Coordination Compounds., Eric Ginsburg

Theses and Dissertations

Heparan sulfate (HS), a type of glycosaminoglycan (GAG), has been identified as a ligand for interactions with polynuclear platinum complexes (PPCs). HS is involved in numerous biological processes, and often considered to be extracellular DNA. PPCs interact with HS through the formation of a “sulfate clamp”, where multiple anionic sulfate groups cluster around the cationic PPC. The masking of HS results in the inhibition of enzymatic activity, protein-HS interactions, and other biological processes. PPCs use HS proteoglycans as an method of cellular internalization. By targeting sulfated-GAGs, PPCs can offer precision medicine not currently observed with the FDA approved platinum therapies. …

Finite Element Analysis Of The Mechanisms Of Impact Mitigation Inherent To The North American Bison (Bison Bison) Skull, Andrea Karen Persons

Theses and Dissertations

North American bison (Bovidae: Bison bison) incur blunt impacts to the interparietal and frontal bones when they engage in head-to-head fights. To investigate the impact mitigation of these bones, a finite element analysis of the skull under loading conditions was performed. Based on anatomical and histological studies, the interparietal and frontal bones are both comprised of a combination of haversian and plexiform bone, and are both underlain by bony septa. Additionally, the interparietal bone is thicker than the frontal. Data regarding the mechanical properties of bison bone are scarce, but the results of a phylogenetic analysis infer that the material …

Syntheses, Characterization, And Preliminary Evaluation Of Potential Ruthenium Anticancer Complexes Containing Schiff Base Ligands, Stephen Mensah

Theses and Dissertations

Platinum-based drugs have over the years been administered in the treatment of tumours.

Unfortunately, platinum resistance and the severe side effects associated with the treatments has necessitated the research for new anti-cancer drugs. Ruthenium(II) and Ruthenium(III) complexes have shown promise as useful alternative anticancer agents. The lead candidates include the Ru(II) complex RAPTA-C, a ruthenium(II)-arene complex [Ru(η6-p-cymene)Cl2(1,3,5-triaza-7-phosphaadamantane)] and the Ru(III) complex NAMI-A [imidazoleH][trans-Ru(imidazole) (dimethyl sulfoxide)Cl4]. Both compounds have shown potent cytotoxic activity in several primary human tumor models. Unfortunately, NAMI-A could not advance in clinical evaluations due to limited efficacy in vivo, while the clinical evaluation of RAPTA-C is unknown. …

Adult And Juvenile Rats Differentially Express Mpfc Glua2 Following Traumatic Memory Retrieval, Edgar Rodriguez

Theses and Dissertations

To advance our understanding of how traumatic memories are modulated between adults and juveniles, we characterize the AMPAr subunits, GluA1, GluA2, GluA3 in the mPFC of rodents following traumatic memory retrieval.

GluA2 was differentially expressed in adults but not juveniles rats. There were no changes in GluA1 or GluA3 expression

Work Ethic Skills And A Liberal Arts Education: Using Work-Integrated Learning In A Liberal Arts Course To Enhance Students' Work Ethic Skills And Demonstrate The Practicality Of A Liberal Arts Education., Jennifer M. Lopes

Theses and Dissertations

To address the gap in employability skills among recent college graduates, the proposed intervention seeks to integrate work ethic skills (WES) into the general education curriculum in a practical, efficient, and effective way to develop and enhance students’ professional skills. Work-integrated learning (WIL), if done properly, is the most effective method for students to learn, practice, and apply professional and academic skills. Problematic is the fact that general education courses have tenuous WIL connections because they are not “job specific. Hence, Kolb’s (1984) experiential learning theory is applied as the theoretical framework for creating effective an meaningful learning experiences via …

Application And Evaluation Of Full-Field Surrogate Models In Engineering Design Space Exploration, Christopher Murray Thelin

Theses and Dissertations

When designing an engineering part, better decisions are made by exploring the entire space of design variations. This design space exploration (DSE) may be accomplished manually or via optimization. In engineering, evaluating a design during DSE often consists of running expensive simulations, such as finite element analysis (FEA) in order to understand the structural response to design changes. The computational cost of these simulations can make thorough DSE infeasible, and only a relatively small subset of the designs are explored. Surrogate models have been used to make cheap predictions of certain simulation results. Commonly, these models only predict single values …