The Interaction of Cofilin with the Actin Filament

The regulation of filamentous actin: F-actin) production from the polymerization of globular actin: G-actin) within the cell is critical for many cell functions. Since actin is found in all cells, understanding how actin-binding-proteins: ABPs) bind and how their regulating mechanisms work is not only important to the basics of cytoskeletal pathways, but also to understanding associated diseases and creating possible therapeutics to combat them. Cofilin is an ABP that plays an important part in the regulation process and in recent times, has come to be known as a player in maintaining a cell\u27s homeostasis. It\u27s activity has been shown to have implications in many diseases, such as Alzheimer\u27s and certain cancers. Cofilin binds and severs actin filaments, leading to depolymerization as well as the creation of new barbed ends. Although some of the details of cofilin\u27s interaction with G-actin have been illuminated through a range of experimental studies, the specific interactions with F-actin have remained much more elusive. As of yet, there are only cryoEM models of cofilin-bound F-actin: where the binding occurs at a 1:1 ratio), which are not high enough resolution and do not show molecular interactions. The focus of this research is to build a model of how cofilin binds F-actin and understand the mechanism of severing. Computational methods, such as protein-protein docking, all atom molecular dynamics: AA MD) simulations, and Coarse Grain MD: CG MD) can help in understanding the interactions between cofilin and F-actin. Iteratively combining these methods with biochemical and mutagenesis experiments to reach a consensus offer a guide towards a more cogent answer. Here in this dissertation, I describe how I built a cofilin and F-actin binding model, with the aid of empirical data. This work allowed me to create several filament models with varying number of bound cofilin, which replicates different binding states of the filament. I also simulated the dynamics of these filaments models to gain insight into filament behavior, particularly twist

First-Principles Point Defect Models In Zr7ni10 And Zr2ni7 Binary Intermetallic Compounds And Their Implications In Nickel-Metal Hydride Batteries

Zr-Ni-based alloys as nickel-metal hydride battery anode materials offer low-cost, flexible and tunable battery performance. Zr7Ni10 is an important secondary phase found in multi-phased AB2 Laves-phase-based metal hydride alloys, and the synergetic effect between the Zr-Ni and the Laves phases allows access to the high hydrogen storage of the Zr-Ni phases despite the lower absorption/desorption kinetics. Zr7Ni10 displays a small solubility window for Zr-rich compositions, while Zr2Ni7, with no solubility window, shows poor capacity with good kinetics. Stability of point defects within the crystal structure allows Zr7Ni10 to maintain the same structure at off-stoichiometric compositions, thus it is theorized that defects may play a role in the difference between the electrochemical behaviors in Zr7Ni10 and Zr2Ni7. Defect models in Zr7Ni10 and Zr2Ni7 compounds computed using a combination of density functional theory and statistical mechanics offer a starting point for understanding the possible roles that point defects have on the performance of Zr-Ni based active negative electrode materials in Ni/MH batteries. Theoretical vacancy and anti-site defect formation energies are calculated and reported for Zr-rich, Ni-rich, and stoichiometric compounds of Zr7Ni10 and Zr2Ni7, and the implications of the defect models on nickel-metal hydride negative electrode active material design and performance are discussed

Computational Modeling Of High-Performance Nickel-Metal Hydride Battery Materials

With 10 million hybrid electric vehicles on the road worldwide powered primarily by nickel-metal hydride (NiMH) batteries, research into this battery chemistry will improve the hybrid vehicle driving experience, extending electric-only driving ranges while reducing emissions and using less gasoline. The transfer, storage and transport of protons and electrons depend strongly on the structural and electrical features of the active material, including multiple phases, defects, and structural and compositional disorder. The contributions of such subtle defects and the difference with the bulk structure can be difficult to discern experimentally. Ab initio calculations such as the ones based on density functional theory have been used to calculate properties and confirm ground state phase stability in AB2 Laves phase alloys. First-principle DFT calculations confirmed a semi-empirical model for C14/C15 Laves phase structure determination for simple binary compounds, and extended the model for more ternary compounds, using the Mg(Cu1-xZnx)2 system, improving the resolution of the model. Cycle stability of NiMH anode materials is strongly correlated to pressure-concentration-temperature isotherm hysteresis measurements, a measure of irreversible losses such as plastic deformation upon hydrogenation and dehydrogenation, and alloy pulverization plays a key pathway for the degradation. First-principle DFT calculations modeled the initial hydrogenation of AB5-type and AB2-type alloys, yielding the initial lattice expansions upon hydrogenation, and correlating to the hysteresis trends, which can help guide the design of long-cycling materials. X-ray diffraction patterns offer subtle but valuable markers that can be correlated to structure and electrochemical performance. Stacking faults direct interrupt (h0l) plane periodicity of nickel hydroxide materials, and through Rietveld refinement and DIFFaX modeling of the different types of stacking faults, the evolution of the stacking faults was tracked over precipitation time for different compositions. We determined which types of stacking faults have a stronger effect on the (101) peak, and the conditions that promote the formation of each type of stacking fault. Electrochemical impedance spectroscopy coupled with equivalent circuit modeling probes the interactions that occur at the surface interfaces, yielding valuable electrical properties and electrochemical kinetics information. Low-temperature performance of NiMH batteries can be improved by dopants to AB2 anode materials, and La and Nd are particularly promising additives that improve both the storage capacity and high-rate dischargeability. We determined the catalytic activity and the surface area contributions to the electrochemical reactions. This study of defects, structural properties, and surface interfaces in battery materials can identify trends that contribute to higher capacity and higher power materials using computational and modeling methods. Understanding the trends provides better insight into how structural properties affect electrochemical processes and will help guide the design for better optimized battery materials

A Heuristic Model of Organizational Boundaries as Contesting Spaces of Betweenness in International Management

This paper examines organizational boundaries as contesting spaces of in betweenness that requires constant negotiations of multi-level cross-cultural differences. Traditionally, boundaries are viewed as relatively static imaginary lines that facilitate flow of information and resource exchanges between organizations and their environments. Membership and cultural identity employ power through separation to elevate the status and legitimacy of insiders over outsider. As dynamic and contested spaces, organizational boundaries are based on processes of construction, deconstruction, and reconstruction in cross cultural relationships. Four significant functions of boundary are demarcation, perimeters, interfaces, and frontiers. Three contestations illustrate different complex problematics in the betweenness of spaces – 1) rise of the modern nation-state with military and political powers; 2) intellectual capital based on accumulation of legitimizing institutional processes and designations with governance structures and regulatory property rights; and 3) e-commerce creating a digital divide that is transcending traditionally understood sovereign boundaries

Poole-Frenkel Effect and Phonon-Assisted Tunneling in GaAs Nanowires

We present electronic transport measurements of GaAs nanowires grown by catalyst-free metal-organic chemical vapor deposition. Despite the nanowires being doped with a relatively high concentration of substitutional impurities, we find them inordinately resistive. By measuring sufficiently high aspect-ratio nanowires individually in situ, we decouple the role of the contacts and show that this semi-insulating electrical behavior is the result of trap-mediated carrier transport. We observe Poole-Frenkel transport that crosses over to phonon-assisted tunneling at higher fields, with a tunneling time found to depend predominantly on fundamental physical constants as predicted by theory. By using in situ electron beam irradiation of individual nanowires we probe the nanowire electronic transport when free carriers are made available, thus revealing the nature of the contacts