Doctor of Philosophy, The Ohio State University, 2024, Biophysics

Fragment-based quantum chemistry methods provide a way to circumvent the steep nonlinear scaling of electronic structure calculations, enabling the investigation of large molecular systems using high-level methods. First, we present calculations on enzyme models containing 500-600 atoms using the many-body expansion (MBE) and compare them to benchmarks where the entire enzyme-substrate complex is described at the same level of density functional theory (DFT). When amino acid fragments contain ionic side chains, the MBE exhibits oscillatory behavior under vacuum boundary conditions, but rapid convergence is restored using low-dielectric boundary conditions. This suggests that full-system gas-phase calculations are unsuitable as benchmarks for assessing errors in fragment-based approximations. A three-body protocol maintains sub-kcal/mol accuracy compared to supersystem calculations, as does a two-body approach combined with a low-cost full-system correction. In the next section, we use fragmentation to compute protein–ligand interaction energies in systems with several thousand atoms. Convergence tests using a minimal-basis semi-empirical method (HF-3c) indicate that two-body calculations, with single-residue fragments and simple hydrogen caps, are sufficient to reproduce interaction energies obtained using conventional supramolecular electronic structure calculations, to with 1 kcal/mol at about 1% of the cost. Additionally, we show that semi-empirical methods can be used as an alternative to DFT, to assess convergence of sequences of quantum mechanics (QM) models (of increasing size) generated by different automated protocols. Two-body calculations afford a low-cost way to construct a “QM-informed” enzyme model. This streamlined, user-friendly approach to building ligand binding-site models requires no prior information or manual adjustments, making it accessible and practical for a wide range of applications. For the latter parts of this work, we will be focusi (open full item for complete abstract)

Committee: John Herbert (Advisor); Sherwin Singer (Committee Member); William Ray (Committee Member) Subjects: Biochemistry; Biology; Biomedical Research; Biophysics; Chemistry; Computer Science; Molecular Biology; Molecular Chemistry; Molecular Physics; Molecules; Physical Chemistry; Physics; Quantum Physics; Technology; Theoretical Physics

Doctor of Philosophy, The Ohio State University, 2021, Biomedical Engineering

The human body is a complex mechanical environment that exposes cells to variations in both passive and active forces, where forces vary depending on tissue type, location, and function. Recent work has been done to analyze how the mechanical environment changes in different disease states and the effects of these changes on organ and cellular function. As a result, there are several well-known changes in in vitro cellular behavior in response to perturbations in the mechanical environment including: cell shape, size, phenotype, and differentiation. While other groups have begun to distinguish key components related to cell sensing of the mechanical environment, the exact mechanism remains poorly understood. The motor-clutch biophysical model describes cytoskeletal dynamics as a balance between substrate adhesion, myosin contractility, and actin polymerization. Initially, the model was hypothesized as a mechanism to explain cellular traction force generation and resultant actin flow. An initial computational formulation of the motor-clutch system demonstrated that it accurately predicts changes in neuronal cell behavior as a function of changes in extracellular substrate stiffness. Here we adapt the computational motor-clutch model to include external substrate motion as a means of simulating cyclic substrate deformation. We then use this adapted model to study the combined effect of cyclic substrate deformation and substrate stiffness on actin cytoskeleton organization and dynamics. The goal of this work was to demonstrate that the motor-clutch model can be used to predict and explain distinct cellular responses to applied cyclic strain. Furthermore, the adapted model allows for the study of experimental parameter spaces that are otherwise difficult to re-create experimentally. We found that the model predicts that applied cyclic stretch significantly impacts actin traction force generation and adhesion dynamics. Importantly, adhesion dynamics are finely co (open full item for complete abstract)

Committee: Keith Gooch PhD (Advisor); Aaron Trask PhD (Committee Member); Thomas Hund PhD (Committee Member); Seth Weinberg PhD (Committee Member) Subjects: Biomedical Engineering

PhD, University of Cincinnati, 2018, Engineering and Applied Science: Aerospace Engineering

Interaction between a deformable elastic body and an internal or external fluid flow alters the flow pattern. This dissertation describes the effects of elasticity on flow in physiological scenarios. The first part of the thesis describes the influence of soft tissue compliance on flow in the upper airways of pediatric Down syndrome (DS) patients and adolescent Polycystic-Ovarian syndrome patients with obstructive sleep apnea (OSA). Computational fluid dynamics (CFD) of airflow is performed in pre and post-operative geometries of the DS pediatric airway to evaluate effectiveness of a surgery and address the importance of including the subject-specific tissue compliance. A tube law approach and a novel image analysis method are then presented to evaluate the circumferential variation in airway compliance for DS patients. An iterative finite element method is then described to non-invasively estimate patient-specific mechanical properties of the upper airway in these patients. The estimated mechanical properties for a single patient are applied to simulate airway obstruction during inspiratory airflow, before and after surgery. Sensitivity to different flow variables is analyzed and an operating map is created to establish the relationship between tissue elasticity and volumetric airflow. The necessity for performing fluid-structure interaction (FSI) in PCOS subjects with OSA is illustrated through a series of strain maps of upper airway tissue. An inverse methodology based on FSI simulations is described to characterize the soft-palate stiffness in these subjects. Differences in pre and post-operative airflow patterns and tissue motion in a PCOS patient are described using computational modeling and compared with the same for a healthy individual. The second part of the study describes computational FSI modeling of aortic blood flow in Turner syndrome (TS). A continuous measurement tool is developed to automatically compute the longitudinal variation in maximum aort (open full item for complete abstract)

Committee: Ephraim Gutmark Ph.D. (Committee Chair); Shaaban Abdallah Ph.D. (Committee Member); Iris Gutmark-Little (Committee Member); Mark Turner Sc.D. (Committee Member) Subjects: Aerospace Materials

Master of Science, University of Akron, 2017, Biomedical Engineering

Delivery of therapeutic fluids such as surfactant solutions into lungs is a major strategy to treat various respiratory disorders. Instilled solutions form liquid plugs in lung airways. The plugs propagate downstream in airways by inspired air or forced ventilation, continuously split at airway bifurcations to smaller daughter plugs and simultaneously lose mass from their trailing menisci, and eventually rupture. A uniform distribution of the instilled liquid in lung airways is expected to increase the treatments success. The uniformity of distribution of instilled liquid in the lungs greatly depends on the splitting of liquid plugs between daughter airways, especially in the first few generations of airways from which airways of different lobes of lungs emerge. To mechanistically understand the liquid plug splitting process, we develop a novel bioengineering approach to computationally design three-dimensional bifurcating airway models using morphometric data of human lungs, fabricate seamless physical models using additive manufacturing, and examine effects of geometry of airways, fluid properties, and flow characteristics on liquid plug splitting. We find that the orientation of bifurcating airways has a major effect on the splitting of liquid plugs between daughter airways and discuss the role of various forces including inertia, gravity, and surface tension using several dimensionless groups. This work provides a fundamental understanding toward developing delivery strategies for uniform distribution of therapeutic fluids in the lungs.

Committee: Hossein Tavana PhD (Advisor); Marnie Saunders PhD (Committee Member); Jae-Won Choi PhD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Fluid Dynamics

MS, University of Cincinnati, 2017, Engineering and Applied Science: Mechanical Engineering

This study develops a polygonal finite element solver for 2-D crack propagation simulation along with a meshing algorithm which creates necessary polygonal mesh. The work starts with a brief literature review of historical development of computational fracture mechanics. After reviewing multiple methods employed for modeling fracture problems, Wachspress formulation is selected for constructing the polygonal finite element solver. Polygonal interpolants are developed using Wachspress' framework and validated using published results. A polygonal meshing algorithm is also developed since conventional finite element meshers do not support domain meshing using higher order polygons. The meshing algorithm is then used to create the mesh and input files for the polygonal finite element solver. The polygonal solver is validated using conventional patch tests. The accuracy and convergence of the method is assessed using classical solid mechanics problems with known analytical solutions. Next, ability to include cracks geometrically is added to the meshing algorithm. The polygonal solver is updated with crack tracking and remeshing capability. A fracture problem is solved using the developed subroutines.

Committee: Yijun Liu Ph.D. (Committee Chair); Woo Kyun Kim Ph.D. (Committee Member); Kumar Vemaganti Ph.D. (Committee Member) Subjects: Mechanical Engineering; Mechanics

Doctor of Philosophy, Case Western Reserve University, 2017, Macromolecular Science and Engineering

Advancement in computational capacity combined with the emergence of efficient algorithms has made the computational studies very powerful and desirable. Despite the great importance of complex fluids such as emulsions, colloidal suspensions, and gels in many applications, some of their physical and mechanical properties remain poorly understood. To understand rheological and mechanical properties of such systems, one needs to understand their properties at different time and length scales through careful multiscale analysis. To answer these questions, we use Dissipative Particle Dynamics as a versatile coarse-grained method to gain a better understanding of different scales and bridge the gap between the microscopic and macroscopic worlds in particulate multicomponent complex fluids. In Chapter 1, briefly, we introduce the DPD mathematical and physical formalism. In Chapter 2, we examine different algorithms to measure the transport properties of a simple DPD fluid and introduce the new computational method to measure the viscosity of DPD liquids under non-equilibrium conditions to account for the numerical instabilities. In Chapter 3, we discuss the properties of multiphasic systems mainly liquids in liquids. We investigate the effect of molecular composition, configuration, and conformability of surface active molecules in stabilizing immiscible mixtures for flat interfaces as well as curved interfaces. The final section of chapter 3 is dedicated to studying the effect of shear deformation on the geometrical evolution of surfactant covered nanodroplets. In chapter 4, we mainly focus on colloidal suspensions and their rheological responses in nonlinear deformation. Through network analysis, we show that the frictional bonds form a percolated network at volume fractions close to jamming while at volume fractions well below jamming the frictional networks are transient and unstable. Measuring viscosity and normal stresses show the discontinuous (open full item for complete abstract)

Committee: Joao Maia (Committee Chair); Gary Wnek (Committee Member); Michael Hore (Committee Member); Daniel Lacks (Committee Member) Subjects: Engineering; Molecular Physics; Morphology; Physical Chemistry; Physics

Doctor of Philosophy, The Ohio State University, 2016, Mechanical Engineering

Analytical solutions to fluid-structure interaction (FSI) problems provide a powerful design tool that has many applications within the automotive industry. The interaction of body panels with various fluid flows is of interest. Automotive panels that are made too thin become susceptible to a phenomenon known as oil-canning. The deformation can be temporary, or if the loading is large enough the panel can snap through, possibly resulting in permanent deformation. One common occurrence of oil-canning is when going through the dryer section of an automatic car wash. For small deformations the panel can shift between various unstable elastic configurations resulting in loud popping noises within the passenger compartment. Large deformations can result in permanent deformation and pitting of the roof panel. Automotive underbody panels are susceptible to water shock loadings that can be generated when driving over a puddle at high speeds. Panels that are made too thin can be permanently deformed or even fail in some cases when the water shock loading is strong enough. Accurate simulations of these scenarios are of interest since thinning body panels provides an easy way to realize significant weight reduction and increase fuel economy. An experimental program is introduced where full size automotive roof panels are subjected to air blast loading. The panels are stamped from thin alloy sheet steel. Roof panels are loaded into a custom test rig and clamped along the weld flanges. The air blast is generated using a commercial air compressor and a 35.1 mm pipe. Force imparted on the panel by the air jet is measured by three load cells and full-field displacement data is captured using three-dimensional digital image correlation (DIC). The flow field is characterized using piezo-resistive pressure transducers placed in a sensor bar apparatus that can be swept across the flow field to generate pressure maps. The pressure transducers are also mounted (open full item for complete abstract)

Committee: Amos Gilat (Advisor); Briam Harper (Committee Member); Chia-Hsiang Menq (Committee Member); Mo-How Shen (Committee Member) Subjects: Mechanical Engineering

Master of Science, Miami University, 2015, Computational Science and Engineering

Fluorite is a common mineral in the earth. Rare Earth Elements (REEs) readily incorporate into fluorite during its growth and are found to be sectorally zoned (i.e., having substitutional concentration differences among the nonequivalent sectors). The underlying causes of sectoral zoning (SZ) of REEs in fluorite are not clear. Also, the mechanisms which differentiate REEs in terms of binding at kinks (i.e., intermediate twists in crystal growth steps) at a crystal surface are still unknown. To study SZ, it is important to explore the dynamics of crystal growth during the adsorption of REEs. In this work, studies have been done to find the internal reasons behind the SZ by simulations and computations at both the atomic and sub-atomic levels using electronic structure methods. Atom Clusters have been modeled which represent the fluorite surface including various REEs at kink sites and nonequivalent faces. Simulation results of electronic structure methods provides detailed explanations to understand the sectoral zoning by exploring the surface structure, energetics and internal morphology for REE adsorption at the kink site of fluorite. Results indicate that adsorption energy differences among faces and differing bond orders among REEs are likely to be principle causes of SZ at the adsorption stage.

Committee: James Moller Dr. (Advisor); John Rakovan Dr. (Committee Member); Fazeel Khan Dr. (Committee Member) Subjects: Chemistry; Computer Science; Mechanical Engineering

Master of Science, The Ohio State University, 2015, Mechanical Engineering

In the last few decades, the finite element method (FEM) has become one of the most important computational tools for the simulation of engineering problems. Due to the increasing popularity of this method, a heavy body of research has focused its attention to the development of advanced FEM-based techniques for the treatment of complex phenomena, including intricate morphologies. This thesis introduces a hierarchical interface-enriched finite element method (HIFEM) for the mesh-independent treatment of the mentioned type of problems. The HIFEM provides a general, and yet easy-to-implement algorithm for evaluating appropriate enrichment in elements cut by multiple interfaces. In the automated framework provided by this method, the construction of enrichment functions is independent of the number and sequence of the geometries introduced to nonconforming finite element meshes. Consequently, the HIFEM algorithm eliminates the need to modify/remove existing enrichment every time a new geometry is added to the domain. The proposed hierarchical enrichment technique can accurately capture gradient discontinuities along material interfaces that are in close proximity, in contact, or intersecting with one another using nonconforming finite element meshes for discretizing the problem. The main contribution of this thesis is the development and implementation of the two-dimensional higher-order HIFEM, and in particular the development of a new hierarchical enrichment scheme for six-note triangular elements. Furthermore, this manuscript presents a new enrichment scheme to simulate strong discontinuities (cracks) in linear elastic fracture mechanics problems. Special attention is given to the available strategies to improve the level of precision and efficiency of the simulations. A detailed convergence study for the enrichment technique that yields the highest precision and the lowest computational cost is also presented. Finally, the author illustrates the application of the (open full item for complete abstract)

Committee: Soheil Soghrati Prof. (Advisor); Rebecca Dupaix Prof. (Committee Member); Marcelo Dapino Prof. (Committee Member) Subjects: Materials Science; Mathematics; Mechanical Engineering

Master of Science, The Ohio State University, 2014, Mechanical Engineering

Characterization of material damage at the interface between two bodies using non-destructive evaluation (NDE) techniques is a field of study that is important from the point of view of both, research and application. In order to provide useful design engineering tools to the practicing engineer in the field of NDE it is necessary to build robust models that can be easily implemented. In the present thesis SH body waves are chosen as a representative candidate to assess material damage and degradation at an interface. In addition a well-established material damage law in the form of cohesive zones from fracture mechanics is considered. The combined effects of transient wave motion and the cohesive boundary condition at the interface are studied in order to develop a methodology for potential use in an NDE application scenario. Parameter variation studies offer promising results to the practicing engineer. Specifically, the trends of displacement and traction along the interface are evaluated between the bonded and damaged material conditions. Parameter variations allow for insight into how altering the material parameters and wave setup affect macro-behavior of the interface.

Committee: Prasad Mokashi (Advisor); Daniel Mendelsohn (Committee Member) Subjects: Engineering; Mechanical Engineering; Mechanics

Master of Science, The Ohio State University, 2013, Mechanical Engineering

A catalytic monolith reactor can be modeled using direct numerical simulation, where all the length scales within a monolith reactor are resolved. This, however, requires the use of a fine grid with millions of cells, which makes it computationally prohibitive. The objective of this thesis is to develop a reduced model for modeling a full-scale catalytic monolith reactor. This model is a computationally inexpensive way of simulating the reacting flow within the entire reactor including the monolith, the pre-monolith and post-monolith regions. The modeling approach developed in this study, termed as sub-grid scale modeling, utilizes a grid that resolves only the largest length scales, while the physics in the smallest (channel or pore) scales are modeled using scale-averaged models, thereby making this approach a computationally efficient alternative to direct numerical simulation. The thesis begins with the development and validation of a turbulence model to simulate turbulent flow in the open regions of the converter. This is followed by the development, verification and validation of a porous media model for flow, heat and mass transfer, since in sub-grid scale modeling framework the monolith reduces to an anisotropic porous medium. A scale-averaged model for simulating the surface chemistry is also incorporated into the porous media model. Finally, all the sub-models are integrated to create a unified model that can simulate the reacting flow through a catalytic monolith reactor. After verifying and validating the individual sub-models, two full-scale validation studies are undertaken. The first validation study involves the catalytic combustion of a premixed hydrogen-air mixture flowing through a monolith containing platinum catalyst. A 12-step reaction mechanism with 4 gas-phase species and 5 surface adsorbed species is used for this study. The second validation study involves the catalytic conversion of a mixture of unburnt hydrocarbon, carbon monoxide, ni (open full item for complete abstract)

Committee: Sandip Mazumder Prof. (Advisor); Ahmet Selamet Prof. (Committee Member) Subjects: Mechanical Engineering

Doctor of Philosophy, The Ohio State University, 2007, Civil Engineering

In marine environments, the placement of a obstacle near an erodible boundary may induce significant changes in the local flow and sediment transport characteristics. In order to quantify these changes, the time-dependent flow field, including locally generated turbulent structures, and the resulting effects on the applied shear at the bed must be accurately predicted. In this effort, these interactions are examined for bottom-seated two- and three-dimensional cylinders in steady current and wave environments with detailed numerical simulations. In steady current, the predicted vortex shedding frequency, downstream recirculation length and upstream separation length around a short cylinder were in reasonable agreement with laboratory data. Upstream of the cylinder, a horseshoe vortex was identified, with vortex extensions deforming edges of the cylinder. In the wake of the cylinder, arch vortices are generated by the shearing of the flow around the cylinder. These vortices are periodically shed from the cylinder. Shed vortices maintain the rotations of the arch vortex and remain connected to the generation region. As these vortices shed from the cylinder, they sweep over the bed, inducing an instantaneous applied shear two to three times larger than the mean value. In wave environments, model predictions of the magnitude, location, and shape of the vortical structures were in good agreement with laboratory data. During the wave half period, the upstream horseshoe vortex and the downstream arch vortex were identified. As the flow reverses, the horseshoe vortex dissipates, and the lee arch vortex flips over the top of the cylinder. Two vortex flipping regimes were identified in wave environments: the single-vortex mode, and the two-vortex mode. The influence of the vortex dynamics on the bed were modeled directly with full sediment transport simulations around a two-dimensional cylinder. Overall shape of the scour hole was in reasonably good agreement with observation (open full item for complete abstract)

Committee: Diane Foster (Advisor) Subjects: Engineering, Civil

Doctor of Philosophy, The Ohio State University, 2005, Welding Engineering

It is difficult to achieve both fast and accurate distortion predictions in large welded structures. This research work was conducted to obtain better understanding and characterization of the plastic deformation that leads to in-plane shrinkage in thin-wall structures. It also aimed to develop a fast and accurate approach for predicting the welding distortion in large thin-wall structures, such automotive body structures. The finite element analysis (FEA) was the tool used in this work to study welding plastic deformation. Before finite element (FE) simulations were carried out for this purpose, a proper FE model was formulated and verified with experiments so that it was capable of rendering accurate distortion computation as well as capturing all the data necessary to investigate the plastic deformation. After verified by the experimental results, the FE model was utilized to perform the welding simulations of three types of simple joints including butt-welded plates, Tee joint, and plate with slot weld. The analysis results were extracted and analyzed to study the in-plane shrinkage and plastic behaviors. The plastic strain distributions were examined in combination with the peak temperatures experienced during welding and the material softening at elevated temperatures. The in-plane shrinkage was correlated to the distribution characteristics of plastic strains, and furthermore the relationships between the plastic strains and their influencing factors were established. The engineering approach was developed based on the findings obtained from the study described above. The research issue of central importance in developing the engineering approach was how to introduce the plastic deformation equivalent to the actual one into the FE model. Temperature load was used in this study and then the central issue became formulating the temperature load, namely its distribution including area of application and magnitude. The engineering approach was then used to predic (open full item for complete abstract)

Committee: Chon Tsai (Advisor) Subjects: Engineering, Mechanical

Master of Science (MS), Ohio University, 1995, Mechanical Engineering (Engineering)

Numerical simulation of titania deposition in a cold-walled impinging jet type APCVD reactor

Committee: M. Alam (Advisor) Subjects: Engineering, Mechanical

Doctor of Philosophy, Case Western Reserve University, 2012, Biomedical Engineering

New approaches to tissue engineering aim to exploit endogenous strategies such as those occurring in prenatal development and recapitulated during postnatal healing. Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for exogenous and endogenous cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. Although a variety of biochemical signals that modulate stem cell fate have been identified, the mechanical signals conducive to guiding pluripotent cells toward specific lineages are less well characterized. Furthermore, not only is spatial and temporal control of mechanical stimuli to cells challenging, but also tissue template geometries vary with time due to tissue ingrowth and/or scaffold degradation. Recent studies show that delivery of cell volume changing dilational (compression, tension) stresses and cell shape changing deviatoric (shear) stresses can be controlled, through cell seeding density and protocol as well as fluid flow, in immature tissue templates designed to mimic mesenchymal condensations. Taken as a whole, these previous studies present an unprecedented opportunity to engineer immature tissue templates that heal and mature, integrating seamlessly with surrounding tissues after implantation in defect zones. I hypothesize that stem cells adapt to mechanical, i.e. shape and volume changing, cues in their environment. Furthermore, I hypothesize that the adaptation of stem cell structure to prevailing mechanical functional demands relates significantly to cell differentiation and maintenance of phenotype. Hence, I, firstly, elucidate the mechanical milieu of seeded stem cells at a subcellular length scale using Computational Fluid Dynamics modeling (CFD) to predict forces at cell boundaries, as well as micro-particle imaging velocimetry to measure forces at cell boundaries. I (open full item for complete abstract)

Committee: MELISSA KNOTHE TATE PhD (Committee Chair); CLARE RIMNAC PhD (Committee Member); DAVID DEAN PhD (Committee Member); JAIKRISHNAN KADAMBI PhD (Committee Member); EBEN ALSBERG PhD (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Biomedical Research; Biophysics

Master of Sciences (Engineering), Case Western Reserve University, 2012, EMC - Aerospace Engineering

The knowledge of the flow field in microchannels is becoming increasingly important with the advent of the ionic wind pump and other microscale heat removal devices. The understanding of this flow field will lead to more effective and improved designs. Non-intrusive microscale particle image velocimetry (PIV) utilizing a microscopic objective lens is used to obtain the velocity field in microchannels. The scales of these channels are similar to those encountered in such devices as the ionic wind pump. Microchannels with dimensions ranging from 0.8 mm to 2 mm are used. Computational fluid dynamics (CFD) models are used to replicate each test, with varying inlet conditions and mesh densities. The CFD flow fields are compared to the PIV results for validation purposes, with relative errors between CFD and PIV typically between 2% and 10%. The agreement between the experimental data and computational results ranged from acceptable to excellent, validating this method. The channel with lowest aspect ratio consistently showed the largest agreement between experimental and numerical values.

Committee: Jaikrishnan R. Kadambi PhD (Advisor); J. Iwan D. Alexander PhD (Committee Member); Vikas Prakash PhD (Committee Member) Subjects: Aerospace Engineering; Fluid Dynamics; Mechanical Engineering