Macromolecular Substances Commons^™

Succinylated Polyethylenimine Gene Delivery Agents For Enhanced Transfection Efficacy, Md. Nasir Uddin

Theses and Dissertations--Chemistry

Gene therapy aims to treat patients by altering or controlling gene expression. Today, most clinical approaches are viral-based due to their inherent gene delivery activity. However, there is still a significant interest in nonviral alternatives for gene delivery, particularly synthetic lipids and polymers, that do not suffer the immunogenicity, high cost, or mutagenesis concerns of viral vectors. Polymeric vectors are of particular interest due to the ability to further tune the polymer properties through the incorporation of additional functional units such as targeting ligands or shielding domains. Polyethylenimine (PEI), a highly cationic polymer, is often considered a benchmark for polymer-based ...

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community ...

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This ...

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

University of New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells ...

Assessment Of The Use Of Low Molecular Weight Diblock Copolymers For The Formation Of Stable, Tunable Droplet Interface Bilayers, Joseph Tawfik

Masters Theses

This thesis presents the use of diblock copolymers, poly(butadiene)-b-poly(ethylene oxide) (PB_m PEO_n) and poly(isoprene)-b-poly(ethylene oxide) (PI_mPEO_n), as amphiphilic molecular building blocks for the formation of synthetic polymer bilayer membranes using the droplet interface bilayer (DIB) technique. The DIB technique makes use of the self-assembly of amphiphilic macromolecules along oil-water droplet interfaces that can then be physically connected for the construction of liquid supported macromolecular bilayers at the droplet interface. These bilayer membranes are capable of hosting both naturally occurring and synthetic protein channels. This technique has been used to ...

Platelets Fuel The Inflammasome Activation Of Innate Immune Cells, Verena Rolfes, Lucas Secchim Ribeiro, Eicke Latz, Moshe Arditi, Bernardo Simoes Franklin

Open Access Publications by UMass Chan Authors

The inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogeneous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets boost the inflammasome capacity of human macrophages and neutrophils and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC oligomerization, caspase-1 activity, and IL-1beta secretion. Platelets influence IL-1beta production in vivo, and blood platelet counts correlate with plasmatic IL-1beta levels in malaria. Furthermore, we reveal an enriched platelet gene signature among ...

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on ...

Synthesis And Characterization Of Pamam-Fatty Acid “Janus-Type” Dendritic Hybrids For Biomedical Applications, Abigail Grace Barker

Honors Theses

Janus dendrimers are amphiphilic macromolecules that have shown promising potential in the biomedical field. Due to their unique structure and properties, these branched block copolymers have the ability to self-assemble into bioinspired spherical nanoaggregates. Because they possess a hydrophobic and hydrophilic moiety, these aggregates show potential as drug delivery systems that can transport both hydrophobic and hydrophilic drugs. However, many of the proposed dendrimer systems suffer from certain weaknesses that hinder their practical usage as clinical treatment options. Some of these shortcomings include specificity, solubility, size, surface charge, and mechanical properties. To combat these problems, we synthesized and characterized a ...

The Development And Evaluation Of Alginate Nanofibers As A Neuroprotective Nano-Scaffold For Amyotrophic Lateral Sclerosis (Als), Julia Bielanin

Chemistry & Biochemistry Undergraduate Honors Theses

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder characterized in pathology by a significant loss of upper and lower motor neurons, leading to muscle wasting and loss of voluntary movement. There are about 6,000-8,000 new cases of ALS diagnosed per year in the U.S., with a fatal outcome within 2 to 4 years (on average) after diagnosis. There are only two FDA approved drugs for treating ALS. Both are very expensive and only have modest benefits for patients. The population is in dire need of more affordable and effective medicine for the treatment of ALS ...

‘Am I Turning Into A Man?’ Experiences Of Pakistani Women With Pcos, Rida E Zehra Zaidi

MSJ Capstone Projects

According to the National Institutes of Health, 20 – 25% of all regularly ovulating women have PCOS. This disorder has a range of visible symptoms including excessive weight gain, hirsutism, acne, and hair loss among others. These symptoms make it difficult for women with the syndrome to fit the femininity ideals of the society, as it demands female bodies to be slim, smart, hair less, and to have porcelain skin and regular menstrual cycles. Women with PCOS and other health problems in Pakistan spend all their lives fighting unnecessary battles. This struggle has severe impacts on their physical and mental well-being.

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in ...

Macromolecular Prodrug For The Treatment Of Ulcerative Colitis, Yuanyuan Sun

Theses & Dissertations

Ulcerative colitis is a chronic inflammatory bowel disease affecting the colon. More than 1 million Americans are affected, with the annual economic burden up to 14.9 billion in the United States. By far, ulcerative colitis still lacks the cure and the current treatment strategies are limited due to severe side effects and in-sufficient efficacy. The tofacitinib (Xeljanz) is the only approved oral medication by for adults with moderately-to-severely-active ulcerative colitis. But the related side effects and serious infections still have to be resolved. In the previous study in our lab, the researchers have successfully developed and characterized multiple hy-drophilic ...

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of ...

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Graduate Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However ...

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the ...

Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox

Chancellor’s Honors Program Projects

No abstract provided.

Towards An Arthritis Flare-Responsive Drug Delivery System, Nitin Joshi, Ellen M. Gravallese, Joerg Ermann, Jeffrey M. Karp

Open Access Publications by UMass Chan Authors

Local delivery of therapeutics for the treatment of inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug delivery method that titrates drug release to arthritis activity would represent an attractive paradigm in IA therapy. Here we report the development of a hydrogel platform that exhibits disassembly and drug release controlled by the concentration of enzymes expressed during arthritis flares. In vitro, hydrogel loaded with triamcinolone acetonide (TA) releases drug on-demand upon exposure to enzymes or synovial fluid from patients with rheumatoid arthritis. In arthritic mice, hydrogel loaded with a fluorescent ...

Enhancing Clot Properties Through Fibrin-Specific Self-Cross-Linked Peg Side-Chain Microgels, Nicole Welsch, Ashley C. Brown, Thomas H. Barker, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Excessive bleeding and resulting complications are a major cause of death in both trauma and surgical settings. Recently, there have been a number of investigations into the design of synthetic hemostatic agents with platelet-mimicking activity to effectively treat patients suffering from severe hemorrhage. We developed platelet-like particles from microgels composed of polymers carrying polyethylene glycol (PEG) side-chains and fibrin-targeting single domain variable fragment antibodies (PEG-PLPs). Comparable to natural platelets, PEG-PLPs were found to enhance the fibrin network formation in vitro through strong adhesion to the emerging fibrin clot and physical, non-covalent cross-linking of nascent fibrin fibers. Furthermore, the mechanical reinforcement ...

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved ...

Cannabinoid Receptor 2 And C-X-C Chemokine Receptor 4 Interact To Abrogate Cxcl12-Mediated Cellular Response, Christopher James Coke

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2 ...