Thesis (Ph.D)--Mechanical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Jianmin Qu; Committee Member: David McDowell; Committee Member: Elisa Riedo; Committee Member: Min Zhou; Committee Member: Mo Li.

The biological functions of proteins often rely on structural changes and the rates at which these conformational changes occur. Studies show that regions of a protein which are known to be involved in enzyme catalysis or in contact with the substrate are identifiable by NMR spectroscopy to be more flexible, evidenced through measuring order parameters of specific bond vectors. While generalized NMR can allow for detailed characterization of the extent and time scales of these conformational fluctuations, NMR cannot easily produce the structures of sparsely populated intermediates nor can it produce explicit complex atomistic-level mechanisms needed for the full understanding of such processes. Practically, preparing a protein with appropriate isotropic enrichment to study a set of specific bond vectors experimentally is challenging as well. Oftentimes, measuring the dynamics of neighboring bond vectors are necessitated. Detailed studies of the coupling interactions among specific residues and protein regions can be fulfilled by the use of molecular dynamics (MD) simulations. However, MD simulations rely on the ergodic hypothesis to mimic experimental conditions, requiring long simulation times. Simulations are additionally limited by the availability of accurate and reliable molecular mechanics force fields, which continue to be improved to better match experimental data. Much can also be learned from chemical theory and simulations to improve the methods in which experimental data is processed and analyzed. The overarching goals of this thesis are to improve upon the results generated by existing methods in NMR spin relaxation spectroscopy, whether that be through: (i) improving analytical techniques of raw NMR data or through (ii) supporting experimental results with atomistically-detailed MD simulations. The majority of this work is exemplified through the protein Escherichia coli ribonuclease HI (ecRNH). Ribonuclease HI (RNase H) is a conserved endonuclease responsible for cleaving the RNA strand of DNA/RNA hybrids in many biological processes, including reverse transcription of the viral genome in retroviral reverse transcriptases and Okazaki fragment processing during DNA replication of the lagging strand. RNase H belongs to a broader superfamily of nucleotidyl-transferases with conserved structure and mechanism, including retroviral integrases, Holliday junction resolvases, and transposases. RNase H has historically been the subject of many investigations in folding, structure, and dynamics. In support of the first aim, we discuss new methods of obtaining more precise experimental results for order parameters and time constants for the ILV methyl groups. Deuterium relaxation rate constants are determined by the spectral density function for reorientation of the C-D bond vector at zero, single-quantum, and double-quantum 2H frequencies. We interpolate relaxation rates measured at available NMR spectrometer frequencies in order to perform a joint single/double-quantum analysis. This yields approximately 10-15% more precise estimates of model-free parameters and consequently provides a general strategy for further interpolation and extrapolation of data gathered from existing NMR spectrometers for analysis of 2H spin relaxation data in biological macromolecules. In support of the second aim, we calculate autocorrelation functions and generalized order parameters for the ILV methyl side chain groups from MD simulation trajectories to assess the orientational motions of the side chain bond vectors. We demonstrate that motions of the side chain bond vectors can be separated into: (i) fluctuations within a given dihedral angle rotamer, (ii) jumps among the different rotamers, and (iii) motions from the protein backbone itself, through the C-alpha carbon. We are able to match order parameters of constitutive motions to conventionally calculated order parameters with an R2= 0.9962, 0.9708, and 0.9905 for Valine, Leucine, and Isoleucine residues, respectively. Some longer side chain residues such as Leucine and Isoleucine have correlated χ1 and χ2 dihedral angle rotational motions. This provides a method of evaluating the relative contributions of each constitutive motion towards the overall flexibility of a side chain. Multiple contributors of motion are possible for intermediate and low order parameters, signifying more flexible residues. While developing protocols for MD simulations, we evaluate the effects of running 1-microsecond long simulations and compare them to solution state NMR spectroscopy. If the overall tumbling time is removed from the simulation, then analysis blocks of 5-10 times the tumbling time is optimal to eliminate contributions from slower dynamics, which would not normally be measured in solution state NMR spectroscopy. We also assess the quality of the TIP4P(-EW) water model over TIP3P; although TIP4P simulates the isotropic tumbling time well for ecRNH, internal motions are equally not affected by either water model due to well-segregated motions. Additionally, the TIP4P water model does not appear to be able to replicate an axially symmetric shape for ecRNH (ecRNH is mostly spherical and only slightly axially symmetric). The final work of this thesis returns to the first overarching aim; we develop a specialized method that utilizes probability distribution functions to model spectral density functions. We derive the inverse Gaussian probability distribution function from general properties of spectral density functions at low and high frequencies for macromolecules in solution, using the principle of maximum entropy. The resulting model-free spectral density functions are finite at a frequency of zero and can be used to describe distributions of either overall or internal correlation times using the model-free ansatz. The approach is validated using 15N backbone relaxation data for the intrinsically disordered, DNA-binding region of the bZip transcription factor domain of the Saccharomyces cerevisiae protein GCN4, in the absence of cognate DNA.

Indiana University-Purdue University Indianapolis (IUPUI) / In this thesis, a high- fidelity multibody dynamics model of a backhoe for simulating the digging operation is developed using the DIS (Dynamic Interactions Simulator)multibody dynamics software. Sand is used as a sample digging material to illustrate the model. The backhoe components (such as frame, manipulators links,track segments, wheels and sprockets) are modeled as rigid bodies. The geometry of the major moving components of the backhoe is created using the Pro/E solid modeling software. The components of the backhoe are imported to DIS and connected using joints (revolute, cylindrical and prismatic joints). Rotary and linear actuators along with PD (Proportional-Derivative) controllers are used to move and steer the backhoe and to move the backhoes manipulator in the desired trajectory. Sand is modeled using cubic shaped particles that can come into contact with each other, the backhoes bucket and ground. A cubical sand particle contact surface is modeled using eight spheres that are rigidly glued to each other to form a cubical shaped particle, The backhoe and ground surfaces are modeled as polygonal surfaces. A penalty technique is used to impose both joint and normal contact constraints (including track-wheels, track-terrain, bucket-particles and particles-particles contact). An asperity-based friction model is used to model joint and contact friction. A Cartesian Eulerian grid contact search algorithm is used to allow fast contact detection between particles. A recursive bounding box contact search algorithm is used to allow fast contact detection for polygonal contact surfaces and is used to detect contact between: track and ground; track and wheels; bucket and particles; and ground and particles. The governing equations of motion are solved along with joint/constraint equations using a time-accurate explicit solution procedure. The sand model is validated using a conical hopper sand flow experiment in which the sand flow rate during discharge and the angle of repose of the resulting sand pile are experimentally measured. The results of the conical hopper simulation are compared with previously published experimental results. Parameter studies are performed using the sand model to study the e ffects of the particle size and the orifi ces diameter of the hopper on the sand pile angle of repose and sand flow rate. The sand model is integrated with the backhoe model to simulate a typical digging operation. The model is used to predict the manipulators actuator forces needed to dig through a pile of sand. Integrating the sand model and backhoe model can help improving the performance of construction equipment by predicting, for various vehicle design alternatives: the actuator and joint forces, and the vehicle stability during digging.

In potable water preparation, chlorination is the last step before the potable water enters the distribution network. Umgeni Water Wiggins Waterworks feeds the Southern areas of Durban. A reservoir at this facility holds treated water before it enters the distribution network. To ensure an adequate disinfection potential within the network, the free chlorine concentration in the water leaving the reservoir at the Umgeni Water Wiggins Waterworks should be between 0.8 and 1.2 mg/L. The aim of this study was to develop an effective strategy to predict and control the chlorine concentration at the exit of the reservoir. This control problem is made difficult by the wide variations in flow and level in the reservoirs, together with reactive decay of the chlorine concentration. A Computational Fluid Dynamic study was undertaken to gain understanding of the physical processes operating in the reservoir (FLUENT software). As this kind of modelling is not yet applicable for real-time control, compartment models have been created to simulate the behaviour of the reservoir as closely as possible, using the results of the fluid dynamic simulation. These compartment models were initially used in an extended Kalman filter (MATLAB software). In a first step, they were used to estimate the kinetic factor for chlorine consumption and in a second step, they predicted the chlorine concentration at the outlet of the reservoir. The comparison between predictions and data, allowed the validation of the compartment models. A predictive control strategy was developed using a Dynamic Matrix Controller, and tested offline on the compartment models. The controller manipulated the chlorine concentration in the inlet of the reservoir in order to control the chlorine concentration in the outlet of the reservoir. Finally, the simplest compartment model was implemented on-line, using the Adroit SCADA system of the plant, in the form of a Kalman filter to estimate the chlorine decay constant, as well as a predictive model, using this continuously-updated decay parameter. The adaptive Dynamic Matrix Controller using this model was able to control the outlet chlorine concentration quite acceptably, and further improvements of the control performance are expected from ongoing tuning. / Thesis (M.Sc.Eng.)-University of Natal, Durban, 2003.

A study of Molecular Dynamics using computational methods and modeling provides the understanding on the interaction of the atoms, properties, structure, and motion and model phenomenon. There are numerous commercial tools available for simulation, analysis and visualization. However any particular tool does not provide all the functionalities. The main objective of this work is the development of the visualization tool customized for our research needs to view the three dimensional orientation of the atom, process the simulation results offline, able to handle large volume of data, ability to display complete frame, atomic trails, and runtime response to the researchers' query with low processing time. This thesis forms the basis for the development of such an in-house tool for analysis and display of simulation results based on Open GL and MFC. Advantages, limitations, capabilities and future aspects are also discussed. The result is the system capable of processing large amount of simulation result data in 11 minutes and query response and display in less than 1 second. / by Meha Garg. / Thesis (M.S.C.S.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.

Molecular dynamics is a computer simulation technique for expressing the ultimate details of individual particle motions and can be used in many fields, such as chemical physics, materials science, and the modeling of biomolecules. In this thesis, we study visualization and pattern mining in molecular dynamics simulation. The molecular data set has a large number of atoms in each frame and range of frames. The features of the data set include atom ID; frame number; position in x, y, and z plane; charge; and mass. The three main challenges of this thesis are to display a larger number of atoms and range of frames, to visualize this large data set in 3-dimension, and to cluster the abnormally shifting atoms that move with the same pace and direction in different frames. Focusing on these three challenges, there are three contributions of this thesis. First, we design an abnormal pattern mining and visualization framework for molecular dynamics simulation. The proposed framework can visualize the clusters of abnormal shifting atom groups in a three-dimensional space, and show their temporal relationships. Second, we propose a pattern mining method to detect abnormal atom groups which share similar movement and have large variance compared to the majority atoms. We propose a general molecular dynamics simulation tool, which can visualize a large number of atoms, including their movement and temporal relationships, to help domain experts study molecular dynamics simulation results. The main functions for this visualization and pattern mining tool include atom number, cluster visualization, search across different frames, multiple frame range search, frame range switch, and line demonstration for atom motions in different frames. Therefore, this visualization and pattern mining tool can be used in the field of chemical physics, materials science, and the modeling of biomolecules for the molecular dynamic simulation outcomes. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Atherosclerosis, the leading cause of mortality in Western societies, affects large elastic arteries, causing focal deposition of proliferative inflammatory and lipid-laden cells within the artery. Several risk factors have been causally implicated in the ???reaction to injury??? hypothesis first described by Ross in 1969. The ???injury??? sustained by endothelial cells may be either mechanical or chemical. Environmental factors have a role in the production of chemical agents that are injurious to the endothelium. Mechanical stresses such as wall tensile stress are proportional to systemic blood pressure and pulse pressure. Essentially, these systemic pressures are fairly evenly distributed throughout the circulation. However, atherosclerotic lesions characteristically occur at focal sites within the human vasculature; at or near bifurcations, within the ostia of branch arteries and at regions of marked or complex curvature, where local haemodynamic abnormalities occur. The most discussed haemodynamic factor seems to be low or highly oscillating wall shear stress which exists on the outer wall of bifurcations and on the inner aspect of curving vessels. The magnitude of these haemodynamic forces may not be great but the subtleties of their variable spatial distribution may help to explain the multifocal distribution of atherosclerotic plaques. With the altered haemodynamics there is endothelial injury and phenotypic changes in the endothelium result, which in turn lead to endothelial cell dysfunction. These haemodynamic variables are difficult to measure directly in vivo. In this work a novel model is developed utilising human autologous vein bypass grafts as a surrogate vessel for the observation of pathological structural changes in response to altered haemodynamics. The influence of haemodynamic factors (such as wall shear stress) in the remodeling of the vein graft wall and the pathogenesis of Myointimal Hyperplasia (MIH) and resultant wall thickening in femoral bypass grafts is analysed. The haemodynamic determinants of MIH (which have been established in many animal models) are similar to those implicated in atherosclerosis. The accelerated responses of the vein (Intimal hyperplasia develops much more rapidly than atherosclerotic lesions in native vessels) make it an ideal model to expediently examine the hypothesised relationships prospectively in an in vivo setting. Furthermore, the utilisation of in vivo data acquired from non-invasive diagnostic methods (such as Magnetic Resonance Angiography (MRA) and Duplex ultrasound) combined with the application of state-of-the-art Computational Fluid Dynamic (CFD) techniques makes the model essentially non-invasive. The following hypotheses are examined: 1) regions of Low shear and High tensile stress should develop disproportionately greater wall thickening, 2) regions of greater oscillatory blood flow should develop greater wall thickening, and 3) regions of lower wall shear should undergo inward (or negative) remodelling and result in a reduction in vessel calibre. The conclusions reached are that abnormal haemodynamic forces, namely low Time-averaged Wall Shear Stress, are associated with subsequent wall thickening. These positive findings have great relevance to the understanding of vein graft MIH and atherosclerosis. It was also evident that with non-invasive data and CFD techniques, some of the important haemodynamic factors are realistically quantifiable (albeit indirectly). The detection of parameters known to be causal in the development of graft intimal hyperplasia or other vascular pathology may improve ability to predict clinical problems. From a surgical perspective this might be employed to facilitate selection of at-risk grafts for more focused postoperative surveillance and reintervention. On a broader stage the utilisation of such analyses may be useful in predicting individuals at greater risk of developing atherosclerotic deposits, disease progression, and the likelihood of clinical events such as heart attack, stroke and threat of limb loss.

Hollow fibre and spiral wound membrane (SWM) modules are the most common commercially available membrane modules. The latter dominate especially for RO, NF and UF and are the focus of this study. The main difficulty these types of modules face is concentration polarisation. In SWM modules, the spacer meshes that keep the membrane leaves apart also help reduce the effects of concentration polarisation. The spacer filaments act as flow obstructions, and thus encourage flow destabilisation and increase mass transfer enhancement. One of the detrimental aspects of the use of spacers is an increase of pressure losses in SWM modules. This study analyses the mechanisms that give rise to mass transfer enhancement in narrow spacer-filled channels, and investigates the relationship between flow destabilisation, energy losses and mass transfer. It shows that the regions of high mass transfer on the membrane surface correlate mainly with those regions where the fluid flow is towards the membrane. Based on the insights gained from this analysis, a series of multi-layer spacer designs are proposed and evaluated. In this thesis, a Computational Fluid Dynamics (CFD) model was used to simulate steady and unsteady flows with mass transfer in two- and three-dimensional narrow channels containing spacers. A solute with a Schmidt number of 600 dissolving from the wall and channel Reynolds numbers up to 1683 were considered. A fully-developed concentration profile boundary condition was utilised in order to reduce the computational costs of the simulations. Time averaging and Fourier analysis were performed to gain insight into the dynamics of the different flow regimes encountered, ranging from steady flow to vortex shedding behind the spacer filaments. The relationships between 3D flow effects, vortical flow, pressure drop and mass transfer enhancement were explored. Greater mass transfer enhancement was found for the 3D geometries modelled, when compared with 2D geometries, due to wall shear perpendicular to the bulk flow and streamwise vortices. Form drag was identified as the main component of energy loss for the flow conditions analysed. Implications for the design of improved spacer meshes, such as extra layers of spacer filaments to direct the bulk flow towards the membrane walls, and filament profiles to reduce form drag are discussed.

published_or_final_version / Civil Engineering / Master / Master of Philosophy

Hollow fibre and spiral wound membrane (SWM) modules are the most common commercially available membrane modules. The latter dominate especially for RO, NF and UF and are the focus of this study. The main difficulty these types of modules face is concentration polarisation. In SWM modules, the spacer meshes that keep the membrane leaves apart also help reduce the effects of concentration polarisation. The spacer filaments act as flow obstructions, and thus encourage flow destabilisation and increase mass transfer enhancement. One of the detrimental aspects of the use of spacers is an increase of pressure losses in SWM modules. This study analyses the mechanisms that give rise to mass transfer enhancement in narrow spacer-filled channels, and investigates the relationship between flow destabilisation, energy losses and mass transfer. It shows that the regions of high mass transfer on the membrane surface correlate mainly with those regions where the fluid flow is towards the membrane. Based on the insights gained from this analysis, a series of multi-layer spacer designs are proposed and evaluated. In this thesis, a Computational Fluid Dynamics (CFD) model was used to simulate steady and unsteady flows with mass transfer in two- and three-dimensional narrow channels containing spacers. A solute with a Schmidt number of 600 dissolving from the wall and channel Reynolds numbers up to 1683 were considered. A fully-developed concentration profile boundary condition was utilised in order to reduce the computational costs of the simulations. Time averaging and Fourier analysis were performed to gain insight into the dynamics of the different flow regimes encountered, ranging from steady flow to vortex shedding behind the spacer filaments. The relationships between 3D flow effects, vortical flow, pressure drop and mass transfer enhancement were explored. Greater mass transfer enhancement was found for the 3D geometries modelled, when compared with 2D geometries, due to wall shear perpendicular to the bulk flow and streamwise vortices. Form drag was identified as the main component of energy loss for the flow conditions analysed. Implications for the design of improved spacer meshes, such as extra layers of spacer filaments to direct the bulk flow towards the membrane walls, and filament profiles to reduce form drag are discussed.