Biological and Chemical Physics Commons^™

The Influence Of Allostery Governing The Changes In Protein Dynamics Upon Substitution, Joseph Hess

All Dissertations

The focus of this research is to investigate the effects of allostery on the function/activity of an enzyme, human immunodeficiency virus type 1 (HIV-1) protease, using well-defined statistical analyses of the dynamic changes of the protein and variants with unique single point substitutions ¹. The experimental data¹ evaluated here only characterized HIV-1 protease with one of its potential target substrates. Probing the dynamic interactions of the residues of an enzyme and its variants can offer insight of the developmental importance for allosteric signaling and their connection to a protein’s function. The realignment of the secondary structure elements can …

Characterization Of Boreal-Arctic Vegetation Growth Phases And Active Soil Layer Dynamics In The High-Latitudes Of North America: A Study Combining Multi-Year In Situ And Satellite-Based Observations, Michael G. Brown

Dissertations, Theses, and Capstone Projects

This dissertation examined the seasonal freeze/thaw activity in boreal-Arctic soils and vegetation physiology in Alaska, USA and Alberta, Canada, using in situ environmental measurements and passive microwave satellite observations. The boreal-Arctic high-latitudes have been experiencing ecosystem changes more rapidly in comparison to the rest of Earth due to the presently warming climatic conditions having a magnified effect over Polar Regions. Currently, the boreal-Arctic is a carbon sink; however, recent studies indicate a shift over the next century to become a carbon source. High-latitude vegetation and cold soil dynamics are influenced by climatic shifts and are largely responsible for the regions …

Flash-Rt: Using High-Dose Radiation For Clinical Radiation Therapy, Deja Stubbs

University Honors Theses

This paper is a literature review on the possible mechanisms behind the FLASH effect and why such research can advance the world of radiology treatment by modifying current clinical linear accelerators to produce ultra-high doses of radiation. Radiation Therapy, also known as external Beam Radiation Therapy, is a common type of cancer treatment. Globally, cancer is the second-leading cause of death, but has seen an increase in survival rates over the past couple of years. Cancer can develop in almost any part of the body since cancer is defined as uncontrolled cell growth. The FLASH Effect is seen when treating …

Optimization Of Flagellar Locomotion In The Low Reynolds Number Regime, Aidan M. Trodden, Aidan M. Trodden

Physics

This report investigates the computational and theoretical techniques - modeled by E. Lauga and C. Eloy - used to optimize the shape of an activated flagellum for enhanced cell motility. Cell motility is ubiquitous and has a large affect on biological systems such as marine life ecosystems, reproduction, and infection. The physical principles governing flagellar propulsion are explored using computational fluid dynamics simulations, mathematical modeling, and the sequential quadratic programming (SQP) optimization algorithm. Through iterative refinement, we can identify optimized flagellar shapes that would minimize the energetic cost dependent on a single dimensionless sperm numbers (Sp). The computation of the …

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba

Chemistry & Biochemistry Undergraduate Honors Theses

Hemagglutinin is a protein on the surface of Human Influenza Viruses.¹ It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.⁴ In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.⁴ These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and …

Modelling Cell Population Growth, Mahmood Mazarei

Electronic Thesis and Dissertation Repository

The growth of biological matter, e.g., tumor invasion, depends on various factors, mainly the tissue’s mechanical properties, implying elasticity, stiffness, or apparent viscosity. These properties are impacted by the characteristics of the tissue’s extracellular matrix and constituent cells, including, but not limited to, cell membrane stiffness, cell cytoskeleton mechanical properties, and the intensity and distribution of focal adhesions over the cell membrane. To compute and study the mechanical properties of tissues during growth and confluency, a theoretical and computational framework, called CellSim3D, was developed in our group based on a three-dimensional kinetic division model.

In this work, CellSim3D is …

An Ab Initio Computation Of The Potential Energy Surfaces Of The Dna Bases, Anjali F. Filinovich, Vola Andrianarijaona

Campus Research Day

The potential energy surfaces of atoms in DNA can be analyzed and compared to show how their bonds break. This DNA potential energy reference data is very useful to understanding how DNA damage occurs, however, a dataset of relevant potential energy surfaces is not available for scientific use. We obtain the potential energy surfaces of various atoms in the four DNA bases adenine, thymine, guanine, and cytosine, by moving an atom in these molecules in three orthogonal directions using ORCA, an ab initio quantum chemistry software. Density functional theory is
used to compute potential energies as an atom is moved, …

Analysis And Methodology Of Helical And Flexible Homopolymer Monte Carlo Simulations, Nathan Roberts

Honors College Theses

The purpose of my work is to analyze the results of Monte Carlo simulations of various types of polymers: a helical homopolymer and a flexible homopolymer. Specific applications of Monte Carlo polymer simulations and parallel tempering replica exchanges are presented. Using temporal analysis, I aim to measure the efficiency of each type of simulation as it relates to equilibration time. For the helical homopolymer model, equilibration time is expanded upon to analyze the rate of structure generation and relevant hyper-phase diagram. Stable states for helical homopolymers will use data generated from parallel tempering replica exchange Monte Carlo simulations created by …

Modeling Excited State Processes In Molecular Aggregates By Constructing An Adaptive Basis For The Hierarchy Of Pure States, Leonel Varvelo

Chemistry Theses and Dissertations

Simulating excitation energy transfer (EET) in molecular materials is of crucial importance for the development of and understanding of materials such as organic photovoltaics and photosynthetic systems and further development of novel materials. The Hierarchy of Pure States (HOPS) is an exact framework for the time evolution of an open quantum system in which a hierarchy of stochastic wave functions are propagated in time. The adaptive HOPS (adHOPS) method achieves size-invariant scaling with the number of simulated molecules for sufficiently large aggregates by using an adaptive basis that moves with the excitation through the material. To demonstrate the power of …

Novel As-S-Se Compositions Of Solution-Processed Chalcogenide Thin Films For Infrared Optics, Annabella Orsini

Physics and Astronomy Honors Papers

Chalcogenide glasses (ChGs) have a wide range of interdisciplinary applications. In industry, ChGs are used to vastly improve infrared sight abilities. There are, however, improvements that can be made to the films’ stability, cost, and flexibility. Our project seeks to produce thin films that have these improvements, with capabilities comparable or better than what is widely used in the field. Thin films created through solution-based processes have proven to be much more flexible in comparison to bulk glass versions. Other elements in Group 16, such as Sulfur and Selenium have shown across literature to be a cost-effective alternative to Tellurium …

Developing Carbon Quantum Dots As Multimodal Contrast Agents, Nicholas Whiting

Faculty Scholarship for the College of Science & Mathematics

No abstract provided.

Reconversion Of Parahydrogen Gas In Surfactant-Coated Glass Nmr Tubes, Robert V. Chimenti, James Daley, James Sack, Jennifer Necsutu, Nicholas Whiting

Faculty Scholarship for the College of Science & Mathematics

The application of parahydrogen gas to enhance the magnetic resonance signals of a diversity of chemical species has increased substantially in the last decade. Parahydrogen is prepared by lowering the temperature of hydrogen gas in the presence of a catalyst; this enriches the para spin isomer beyond its normal abundance of 25% at thermal equilibrium. Indeed, parahydrogen fractions that approach unity can be attained at sufficiently low temperatures. Once enriched, the gas will revert to its normal isomeric ratio over the course of hours or days, depending on the surface chemistry of the storage container. Although parahydrogen enjoys long lifetimes …

Minimal Expression Of Dysferlin Prevents Development Of Dysferlinopathy In Dysferlin Exon 40a Knockout Mice, Joe Yasa, Claudia E. Reed, Adam M. Bournazos, Frances J. Evesson, Ignatius Pang, Mark E. Graham, Jesse R. Wark, Brunda Nijagal, Kim H. Kwan, Thomas Kwiatkowski, Rachel Jung, Noah Weisleder, Sandra T. Cooper, Frances A. Lemckert

Chemistry Faculty Publications

Dysferlin is a Ca2+-activated lipid binding protein implicated in muscle membrane repair. Recessive variants in DYSF result in dysferlinopathy, a progressive muscular dystrophy. We showed previously that calpain cleavage within a motif encoded by alternatively spliced exon 40a releases a 72 kDa C-terminal minidysferlin recruited to injured sarcolemma. Herein we use CRISPR/Cas9 gene editing to knock out murine Dysf exon 40a, to specifically assess its role in membrane repair and development of dysferlinopathy. We created three Dysf exon 40a knockout (40aKO) mouse lines that each express different levels of dysferlin protein ranging from similar to 90%, similar to 50% and …

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (⁹⁰Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …

Homopurine Guanine-Rich Sequences In Complex With N-Methyl Mesoporphyrin Ix Form Parallel G-Quadruplex Dimers And Display A Unique Symmetry Tetrad, Ming Ye, Erin V. Chen, Shawn H. Pfeil, Kailey N. Martin, Tamanaa Atrafi, Sara Yun, Zahara Martinez, Liliya A. Yatsunyk

Physics & Engineering Faculty Publications

DNA can fold into G-quadruplexes (GQs), non-canonical secondary structures formed by pi-pi stacking of G-tet-rads. GQs are important in many biological processes, which makes them promising therapeutic targets. We identified a 42-nucleotide long, purine-only G-rich sequence from human genome, which contains eight G- stretches connected by A and AAAA loops. We divided this sequence into five unique segments, four guanine stretches each, named GA1-5. In order to investigate the role of adenines in GQ structure formation, we per-formed biophysical and X-ray crystallographic studies of GA1-5 and their complexes with a highly selective GQ ligand, N-methyl mesoporphyrin IX (NMM). Our data …

Fabrication And Investigation Of Microfluidic Devices That Produce Non-Linear Chemical Gradients, Elijah L. Waters

Electronic Theses and Dissertations

Investigation of cell chemotaxis requires controlled chemical gradients. We investigated microfluidic devices that could enhance small populations' cell assays because of their ability to generate various chemical gradients. Our five designs generate different chemical concentration landscapes that we can easily convert into tools to study cell response to growth factors. Gradient landscapes occurred by splitting and mixing two input fluid concentrations using bifurcations, trifurcations, and Y-mixing junctions in three consecutive steps. Such fluid flow manipulations resulted in nine concentration streams entering a 0.54-mm-wide gradient chamber. The first design used a 1:1 ratio Y-mixer (unbiased) when blending two concentrations, resulting in …

Optical Tweezers: Exerting Force With Light, Gabriella Seifert

Scripps Senior Theses

Photons carry momentum. When a tightly-focused beam of photons hit a particle, they transfer some of their momentum to the particle, exerting a force. Optical tweezers take advantage of this phenomenon to trap (or “tweeze”) a spherical bead just after the focus of a diverging laser beam, creating a potential well that pulls in beads. In this thesis, I predict the force exerted on trapped beads and measure the actual force using an optical tweezers setup that I built. To predict the force, I follow the path of all possible rays from a diverging beam incident on a spherical bead …

Behaviors For Which Deinonychosaurs Used Their Feet, Alexander King

Honors Projects

This paper seeks to show for what purpose deinonychosaurs used their feet. Fowler et al., (2011) showed that D. antirrhopus’s feet were closest in function to accipitrids, as they found it was more built for grasping prey than running.

I answered this question by using 2D images of the feet of three modern birds (Buteo jamaicensis, Phasianus colchicus, and Gallus gallus domesticus), one eudromaeosaur (Deinonychus antirrhopus), and one troodontid (Borogovia gracilicrus). I used ImageJ to apply 73 landmarks to each foot, capturing the variation between species in the metatarsals and pedal phalanges. These data were then uploaded to the software …

A Method For Exploring The Habitability Of Earth-Like Exoplanets: Applications To Tess Objects Of Interest 203 B, 256 B, And 700 D, Paul Bonney

Graduate Theses and Dissertations

The Transiting Exoplanet Survey Satellite (TESS) has and is continuing to discover a multitude of potentially habitable planet candidates. As more planets are detected and confirmed, it becomes increasingly important to strategically search for signs of habitability with which to differentiate and prioritize them for further observation, in particular with the James Webb Space Telescope (JWST). To facilitate this, I have created a method for prioritizing TESS planet candidates based on parameters derived from their light curves and have applied the method to the TESS Candidate Target List (CTL). This data set uses preliminary fits to transit modeling which can …