Engineering Commons^™

Development Of An Integrated Workflow For Nucleosome Modeling And Simulations, Ran Sun

Doctoral Dissertations

Nucleosomes are the building blocks of eukaryotic genomes and thus fundamental to to all genetic processes. Any protein or drug that binds DNA must either cooperate or compete with nucleosomes. Given that a nucleosome contains 147 base pairs of DNA, there are approximately 4^147 or 10^88 possible sequences for a single nucleosome. Exhaustive studies are not possible. However, genome wide association studies can identify individual nucleosomes of interest to a specific mechanism, and today's supercomputers enable comparative simulation studies of 10s to 100s of nucleosomes. The goal of this thesis is to develop and present and end-to-end workflow that serves …

Multiscale Modeling Of Enzyme-Catalyzed Methanol Production By Particulate Methane Monooxygenase, Katherine K. Bearden

Doctoral Dissertations

In this work, the conversion of methane to methanol by the particulate Methane Monooxygenase (pMMO) enzyme is investigated using a multi-scale modeling approach. This enzyme participates in carbon cycling and aids in the removal of harmful atmospheric methane, converting it to methanol. The interaction between pMMO and a neighboring enzyme that is present in the same organism is studied, and the unknown pMMO active site is elucidated and tested for methane oxidation towards the production of methanol.

Fundamental knowledge of pMMO's mechanism is not fully understood. Understanding how this enzyme works in nature will provide information towards designing efficient synthetic …

The Contribution Of Oxidative Stress In The Protein Damage And Dna Lesion In Alzheimer's Disease Neuropathology, Cheng Zhang

Doctoral Dissertations

Glutathione (GSH) plays an essential role in the intracellular antioxidant defense against the oxidant radicals, especially the ·OH radical. To understand the early and progressive cellular changes in Alzheimer's disease (AD) development, we investigated reduced glutathione/oxidized glutathione (GSH/GSSG) status in a double mutated AD transgenic mouse model (B6.Cg-Tg), which carries Swedish amyloid precursor protein mutation (APPswe) and exon 9 deletion of the PSEN1 gene. Likewise, S-glutathionylation (Pr-SSG) is a specific post-translational modification (PTM) of cysteine residues by the addition of glutathione. S-glutathionylated proteins induced by oxidative stress play an essential role in understanding the pathogenesis of the aging …

Micro, Nano Encapsulation Methods For Sustained Release Drug Formulations And Biomimetic Applications, Shantanu Balkundi

Doctoral Dissertations

The Layer-by-Layer (LbL) assembly technique was used to obtain a new type of protein/polyphenol microcapsule based on naturally occurring polyphenol (-)-epigallocatechin gallate (EGCG) and gelatin, type A. The dependence of permeability on the molecular weight of permeating substances was studied and compared with commonly used polyallylamine/polystyrene sulfonate capsules. A quartz crystal microbalance was used to monitor the regularities of EGCG adsorption in alternation with type A and B Gelatins and electrophoretic mobility measurements were used that indicated that the nature of assembly was dependent on Gelatin properties. It was shown that EGCG retains its antioxidant activity in the LbL assemblies. …

Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula

Doctoral Dissertations

Tensin is a large "docking" protein found in the adhesive junctions of animal cells and recruited early in the development of cell-substrate contacts. There it binds to the cytoplasmic domain of integrin β1 and caps the barbed ends of filamentous actin. This forms a rational basis for its implication in a direct role in the mechanics of membrane-cytoskeleton interactions. Tensin provides a physical link between the actin cytoskeleton, integrins, and other proteins at the cell-substrate contacts. Its overall biochemical properties are a function of its domain composition and architecture, i.e., the domains that are present and their relative positions in …

Molecular Modeling Of Proteins And Peptides Related To Cell Attachment In Vivo And In Vitro, Wanhua Zhao

Doctoral Dissertations

Polypeptides constitute half of the dry mass of the cell, they form the bulk of the extracellular matrix (ECM), and they are a common element of extra- and intracellular signaling pathways. There is increasing interest in the development of computational methods in polypeptide and protein engineering on all length scales. This research concerns the development of computational methods for study of polypeptide interactions related to cell attachment in vivo and in vitro.

Polypeptides are inherently biocompatible, and an astronomical range of unique sequences can be designed and realized in massive quantities by modern methods of synthesis and purification. These …

Layer-By-Layer Self -Assembly For Enzyme And Dna Encapsulation And Delivery, Amish Patel

Doctoral Dissertations

Thin wall microcapsules were formed via Layer-by-Layer Self-Assembly of alternate adsorption of oppositely charged polyelectrolyte on microcores. After the core dissolution, empty polymeric shells with 20–25 nm thick walls were obtained. These microcapsules were loaded with Myoglobin, Hemoglobin and Glucose Oxidase by opening capsule pores at low pH and closing them at higher pH. The native structure of the enzyme was not affected due to different treatments. Biocompatible nanoshells were also prepared for encasing DNA. Using the same Layer-by-Layer Self-Assembly approach nanoparticle were constructed containing DNA as one of the layers. The nanoparticles of different architecture were used to deliver …

A High -Order Finite Difference Method For Solving Bioheat Transfer Equations In Three-Dimensional Triple -Layered Skin Structure, Haofeng Yu

Doctoral Dissertations

Investigations on instantaneous skin burns are useful for an accurate assessment of burn-evaluation and for establishing thermal protections for various purposes. Meanwhile, hyperthermia with radiation is important in the treatment of cancer, and it is essential for developers and users of hyperthermia systems to predict, and interpret correctly the biomass thermal and vascular response to heating. In this dissertation, we employ the well-known Pennes' bioheat transfer equation to predict the degree of skin burn and the temperature distribution in hyperthermia cancer treatment.

A fourth-order compact finite difference scheme is developed to solve Pennes' bioheat transfer equation in a three-dimensional single …