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Articles 1 - 11 of 11
Full-Text Articles in Physical Sciences and Mathematics
Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks
Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks
Doctoral Dissertations
Phosphorylated myo-inositol compounds including inositol phosphates (InsPs) as well as the phosphatidylinositol polyphosphate lipids (PIPns) are critical biomolecules that regulate many of the most important biological processes and pathways. They are aberrant in many disease states due to their regulatory function. The same is true of the phospholipid phosphatidylserine (PS) which can serve as a marker to begin apoptosis. However, the full scope of activities of these structures is not clear, particularly since techniques that enable global detection and analysis of the production of these compounds spatially and temporally are lacking. With all of these obstacles in …
Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout
Doctoral Dissertations
Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these …
Mechanistic Studies Of Peptide-Mediated Protein Transport Across Droplet-Interface Bilayers, Jing Huang
Mechanistic Studies Of Peptide-Mediated Protein Transport Across Droplet-Interface Bilayers, Jing Huang
Doctoral Dissertations
Pep-1 is a promising peptide tool that delivers proteins and peptides into cells with conserved bioactivity. Pep-1 has great potential because of the high efficiency and lack of toxicity. The mechanism of Pep-1-mediated transport is not fully understood. In my thesis, droplet-interface bilayer (DIB) has been used for the mechanistic studies of Pep-1. Here, DIB is developed for different functions such as quantitation of protein translocation, solution exchange to a formed bilayer and simultaneous observation of multiple membranes. Research work on Pep-1 with DIB reveals that the negative charge of the inner membrane leaflet plays a significant role in promoting …
Statistical Methods For High Dimensional Data Arising From Large Epidemiological Studies, Hui Xu
Statistical Methods For High Dimensional Data Arising From Large Epidemiological Studies, Hui Xu
Doctoral Dissertations
In this thesis, we propose statistical models for addressing commonly encountered data types and study designs in large epidemiologic investigations aimed at understanding the molecular basis of complex disorders. The motivating applications come from diverse disease areas in Women's Health, including the study of type II diabetes in the Women's Health Initiative (WHI), invasive breast cancer in the Nurses' Health Study and the study of the metabolomic underpinnings of cardiovascular disease in the WHI. We have also put significant effort into making the implementation of the proposed methods accessible through freely available, user-friendly software packages in R. The first chapter …
Relationship Between Structure And Function In Nickel Proteins And Enzymes, Carolyn Carr
Relationship Between Structure And Function In Nickel Proteins And Enzymes, Carolyn Carr
Doctoral Dissertations
Nickel is a rarely used but biologically important metal that is utilized in all three domains of life. In nickel utilizing organisms there is a corresponding trafficking system specifically designed to capture nickel, deliver, and export excess nickel to prevent toxic effects. It is critical to understand the mechanisms by which organisms achieve metal selectivity to duplicate or disrupt this process for the benefit of human health and to further understanding of regulation mechanisms in biology. RcnR is a Ni(II) and Co(II) responsive transcriptional regulator in E. coli. The research reported in this dissertation focuses on the relationship between …
Vitreous Gel Physics, Svetlana Morozova
Vitreous Gel Physics, Svetlana Morozova
Doctoral Dissertations
The transparent vitreous, which fills the posterior cavity of the eye, is incredibly engineered. The charged polyelectrolyte hyaluronic acid (HA) network swells to maintain the pressure in the eye, while stiff collagen type II bundles help absorb any external mechanical shock. Our investigations have contributed to a few key developments related to the physical properties of the vitreous: (1) The stiff collagen network that supports the soft gel network is self-assembled from single triple-helix collagen proteins. Electrostatic interactions drive this assembly, such that the size and concentration are optimized at physiological salt concentrations. The width of the assemblies remarkably changes …
Mechanistic Studies Of Proton Gradient-Driven Protein Translocation By Droplet-Interface Bilayer Techniques, En-Hsin Lee
Mechanistic Studies Of Proton Gradient-Driven Protein Translocation By Droplet-Interface Bilayer Techniques, En-Hsin Lee
Doctoral Dissertations
Transmembrane proton gradient plays a fundamental role in protein translocation across cellular membranes, including the transport of secreted enzymes from bacterial pathogens into host cells. Much attention has been devoted to understanding the machinery of such delivery and how it functions. Over the past decade, translocation of anthrax toxin has been widely studied not only because of its central role in the deadly pathogenesis of Bacillus anthracis, but also because that it is one of the most tractable toxins and thus serves as an attractive model for studying the translocation machinery that is dependent on proton gradient across membrane. …
The Statistical Dynamics Of Nonequilibrium Control, Grant Murray Rotskoff '09
The Statistical Dynamics Of Nonequilibrium Control, Grant Murray Rotskoff '09
Doctoral Dissertations
Living systems, even at the scale of single molecules, are constantly adapting to changing environmental conditions. The physical response of a nanoscale system to external gradients or changing thermodynamic conditions can be chaotic, nonlinear, and hence difficult to control or predict. Nevertheless, biology has evolved systems that reliably carry out the cell’s vital functions efficiently enough to ensure survival. Moreover, the development of new experimental techniques to monitor and manipulate single biological molecules has provided a natural testbed for theoretical investigations of nonequilibrium dynamics. This work focuses on developing paradigms for both understanding the principles of nonequilibrium dynamics and also …
Thiol-Ene Chemistry As An Enabler Of New Polymer Structures And Architectures, Joel M. Sarapas
Thiol-Ene Chemistry As An Enabler Of New Polymer Structures And Architectures, Joel M. Sarapas
Doctoral Dissertations
This dissertation focuses on two distinct projects: the synthesis and design of novel cell penetrating peptides mimics (CPPMs), and the implementation of the thiol-ene click reaction to generate new polymer architectures and chemistries. Guanidinium-rich CPPMs were generated through both ROMP and RAFT polymerizations, allowing for a comparison to be made across polymer backbone chemistries with respect to both siRNA and protein cellular internalization. A particularly effective methacrylate derived block copolymer was able to deliver siRNA to nearly an entire Jurkat T cell population. The thiol-ene reaction was implemented initially within the context of improving material design for solid polymer electrolytes …
A Functional Data Analytic Approach For Region Level Differential Dna Methylation Detection, Mohamed Salem F. Milad
A Functional Data Analytic Approach For Region Level Differential Dna Methylation Detection, Mohamed Salem F. Milad
Doctoral Dissertations
"DNA methylation is an epigenetic modification that can alter gene expression without a DNA sequence change. The role of DNA methylation in biological processes and human health is important to understand, with many studies identifying associations between specific methylation patterns and diseases such as cancer. In mammals, DNA methylation almost always occurs when a methyl group attaches to a cytosine followed by a guanine (i.e. CpG dinucleotides) on the DNA sequence. Many statistical methods have been developed to test for a difference in DNA methylation levels between groups (e.g. healthy vs disease) at individual cytosines. Site level testing is often …
The Maculoprotective Effect Of A Thiol Antioxidant In Retinal Degeneration Models, Hsiu-Jen Wang
The Maculoprotective Effect Of A Thiol Antioxidant In Retinal Degeneration Models, Hsiu-Jen Wang
Doctoral Dissertations
"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among adults, age 60 and older, in developed countries. While oxidative stress is implicated in the pathogenesis of AMD, clinical studies have shown that dietary antioxidants can delay progression of AMD. Currently, there is no FDA-approved treatment for AMD. Therefore, we hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would protect retinal pigment epithelium and impede the progression of retinal degeneration. The goal of this work was to evaluate the efficacy of NACA in preventing retinal pigment epithelial cell and photoreceptor death in AMD models. To achieve this, we …