Biomedical Engineering and Bioengineering Commons^™

Applications Of Capillary Electrophoresis For Studying Serum Albumin Enantioselection Of D,L-Tryptophan Analogs, Jelynn A. Stinson

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The pharmacokinetic difference between drug enantiomers is the impetus for developing analytical techniques to assess enantiomeric purity. Capillary electrophoresis (CE) is an analytical technique that is used for characterizing drug-protein binding. The pitfall to using CE for drug-protein binding studies is protein chiral selectors tend to adsorb onto capillary walls and cause changes in electroosmotic flow that lead to decreased enantioselection and migration time irreproducibility between consecutive injections. The experimental parameters for minimizing the adverse effects of protein adsorption are not clear from the literature.

Rinsing protocols to improve enantioselection and migration time repeatability were developed using the tryptophan-bovine serum …

Application Of The Human-Machine Interaction Model To Multiple Attribute Task Battery (Matb): Task Component Interaction And The Strategy Paradigm, Craig M. Walters

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The Multiple-Attribute Task Battery (MATB) is composed of four simultaneously running components to which a human operator responds. A prior report has quantified information content as a machine input baud rate using the Hick-Hyman and Fitt's Laws for three of the four components and defines a strategy function. This report covers methods to quantify information content of the fourth component, creating a single metric which describes overall task complexity and evaluates human performance and strategy. Six MATB task-scenarios (combinations of two, three, or all four MATB components) each at two input baud rates are evaluated. Subjects were also provided with …

Regulation Of The Transcription And Subcellular Localization Of The Tumor Suppressor Pten By Δnp63Α, Mary Kathryn Leonard

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Non-melanoma skin cancers (NMSCs) are the most common form of cancer in the United States with an estimated 3.5 million new cases each year. Surgical excision is the main treatment for NMSC, but leaves the potential for disfiguring scars and does not fully reduce the risk of recurrence since the surrounding tissue is also sun damaged and may contain tumor-promoting mutations. By understanding the molecular etiology of NMSC we may be able to expand treatment options to more than just resection. Normal epidermal development is dependent upon the expression of the transcription factor p63. Amplification of the ΔNp63α isoform is …

Optimization Of Wsu Total Ankle Replacement Systems, Bradley Jay Elliott

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Total ankle arthroplasty (TAR) is performed in order to reduce the pain and loss of ambulation in patients with various forms of arthritis and trauma. Although replacement devices fail by a number of mechanisms, wear in the polyethylene liner constitutes one of the dominating failure modes. This leads to instability and loosening of the implant. Mechanisms that contribute to wear in the liners are high contact and subsurface stresses that break down the material over time. Therefore, it is important to understand the gait that generates these stresses. Methods to characterize and decrease wear in Ohio TARs have been performed …

The Role Of Amp-Activated Protein Kinase (Ampk) In Hypoxic Chemotransduction By The Carotid Body, Heidi Lynn Jordan

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The carotid bodies are small sensory organs located along the bifurcation of the carotid arteries. They detect changes in blood gases and relay this information to the brain to allow for initiation of appropriate respiratory and cardiovascular responses. A decrease in oxygen (hypoxia) sensed by the carotid body results in an increase in firing of the carotid sinus nerve and ultimately a change in one's breathing pattern. An inability to respond to an acute hypoxic (low oxygen) episode via increased ventilation may result in death or lead to pathological or chronic conditions such as stroke and hypertension (Prabhakar et.al., 2005). …

The Role Of Angiotensin Converting Enzyme (Ace) 2 In A Murine Model Of Insulin Resistance And Albuminuria, Nathan Michael Weir

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Insulin resistance and kidney disease are intimately linked and both independently tied to dysregulation of the renin angiotensin system (RAS). The purpose of this research was to better investigate Angiotensin Converting Enzyme (ACE) 2 as a possible motif in the pathophysiology of these two disease processes. The project was divided into two parts. Part 1 investigated ACE2 KO mice as a model of albuminuria. Part 2 investigated how the lack of ACE2 enzyme affected glucose homeostasis and subsequent albuminuria.

Part 1: The Role of ACE2 in the Progression of Albuminuria. To determine if global loss of ACE2 leads to spontaneous …

'Omic' Evaluation Of The Region Specific Changes Induced By Non-Cholinergic Diisopropylfluorophosphate (Dfp) Exposure In Fischer 344 Rat Brain, Deirdre A. Mahle

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Organophosphorous compounds (OPs) are a class of serine esterase inhibitors that have widespread application as pesticides, veterinary pharmaceuticals and chemical warfare agents. Environmental contamination is ubiquitous. The threat of exposure is a concern for both military and civilian populations. Acute inhibition of acetylcholinesterase by OPs triggers a cholinergic crisis that results in muscle flaccidity, paralysis, convulsions and death. At low doses OPs can alter neuronal differentiation, cell signaling, behavior and cognition through unknown mechanisms. An imbalance of reactive oxygen species may be implicated in the adverse effects of OPs. An integrated approach using both metabolomic and transcriptomic techniques was used …

Limitations Of Functional Recovery Of Stretch Reflex Circuitry After Peripheral Nerve Regeneration, Gabrielle Marie Horstman

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Peripheral nerve regeneration fails to restore complete normal function after surgical repair of severed nerves, and this failure has primarily been attributed to errors in connecting with peripheral targets. However, recent evidence suggests that central deficits remain even after peripheral target reinnervation is largely successful. It has long been established that regeneration fails to restore the stretch reflex despite observation that many of the neural components are intact. Regenerated Ia afferents are largely successful in reinnervating muscle spindles, are capable of encoding stretch, and elicit EPSPs in homonymous motoneurons, while regenerated motor pools are capable of responding to uninjured sources …

System Optimization And Patient Translational Motion Correction For Reduction Of Artifacts In A Fan-Beam Ct Scanner, Zachary Gordon Lee Wise

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In computed tomography (CT) systems, many different artifacts may be present in the reconstructed image. These artifacts can greatly reduce image quality. For our laboratory prototype CT system, a fan-beam/cone-beam focal high-resolution computed tomography (fHRCT) scanner, the major artifacts that affect image quality are distortions due to errors in the reconstruction algorithm's geometric parameters, ring artifacts caused by uncalibrated detectors, cupping and streaking created by beam hardening, and patient-based motion artifacts. Optimization of the system was required to reduce the effects of the first three artifact types, and an algorithm for correction of translational motion was developed for the last. …

Evaluation Of Interpolation And Registration Techniques In Magnetic Resonance Image For Orthogonal Plane Super Resolution Reconstruction, Amir Pasha Mahmoudzadeh

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Super resolution reconstruction (SRR) combines several perspectives of an image (typically low resolution) in order to reconstruct a more complete and comprehensive (higher resolution) image. The aim is to use this concept on magnetic resonance imaging (MRI) data, for which the standard is to scan in several-plane orientation in a 2D fashion. As a result, clinical MRI, functional MRI (FMRI), diffusion weighted imaging (DWI)/diffusion tensor imaging (DTI), and MR angiography (MRA) tend to have high in- plane resolution but low resolution in the slice-select direction. By combining the 2 scans of the orthogonal plane, new 3D images can be reconstructed. …

The Role Of Ca2+ In Central Respiratory Control Neurons Of The Locus Coeruleus: Development Of The Chemosensitive Brake, Ann Nicole Imber

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Chemosensitive LC neurons increase their firing rate in response to increased CO₂ (hypercapnia) in part via inhibition of K⁺ channels. This increase gets smaller during the first two postnatal weeks (neonatal rats aged P3-P16). Alterations of this "accelerating" pathway may account for the developmental changes in the magnitude of the chemosensitive response in LC neurons. Alternatively, Ca²⁺ and Ca²⁺ channels may play a role in the response to hypercapnia, but little is known about the role of Ca²⁺ in central chemosensitivity. Whole cell patch clamp and fluorescence imaging microscopy were used to study a different …

A Mechanism-Based Model To Describe Gabaa Receptor Trafficking And Benzodiazepine Pharmacoresistance During Status Epilepticus, Elaine Alice Merrill

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Status epilepticus (SE) is a perplexing pathology involving a sudden and long disruption of the brain's normal electrical activity. The study of relevant cellular processes has been useful in identifying therapeutic targets. As a result, many novel drugs are being studied which target receptor systems involved in neuronal membrane excitability. Yet, the standard treatment for SE remains benzodiazepines (BZs), a class of GABAA agonist drugs. Unfortunately, the targeted receptors undergo a desensitization mechanism via enhanced endocytosis (receptor trafficking), leading to rapidly reduced BZ efficacy (pharmacoresistance) within minutes of seizure onset. A comprehensive understanding of the complex interplay between the anticonvulsant's …

Regulation Of The Dna Unwinding Element Binding Protein Due-B In The Cell, Yanzhe Gao

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Eukaryotic cells have evolved tightly controlled processes that make sure the entire genome gets replicated accurately, once per cell cycle. This tight control is fulfilled by degrading replication proteins after their function is carried out, changing their cellular location or by post-translational modification of replication factors to regulate their function. Phosphorylation events carried out by CDKs (cyclin dependent kinases) and DDKs (Dbf4 dependent kinases) play crucial roles in this regulation.

The DNA unwinding element binding protein (DUE-B) is an essential replication protein that binds to the human c-myc DNA replication origin. In this study, I find that DUE-B is also …

Influence Of Design Parameters On Cup-Stem Orientations For Impingement Free Range Of Motion In Hip Implants, Dishita Prakashbhai Patel

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The objective of this investigation is to determine the optimum positions of the prosthesis in total hip arthroplasty that produce least amount of impingement. Theoretical ranges of six basic hip motions were determined under walking, stumbling, internal rotation at 90 flexion and external rotation at 0 extension with 15 abduction, using mathematical models and validated for impingement using finite element analysis. A generalized approach, where impingement does not occur, was developed in this study to understand influence of design parameters such as head-neck ratio, neck-shaft angle, oscillation angle, and stem offset on cup-stem orientations such as cup inclination, cup anteversion, …

A Validation Of A Prototype Dry Electrode System For Electroencephalography, Jason Monnin

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Current physiologically-driven operator cognitive state assessment technology relies primarily on electroencephalographic (EEG) signals. Traditionally, gel-based electrodes have been used; however, the application of gel-based electrodes on the scalp requires expertise and a considerable amount of preparation time. Additionally, discomfort can occur from the abrasion of the scalp during preparation, and the electrolyte will also begin to dry out over extended periods of time. These drawbacks have hindered the transition of operator state assessment technology into an operational environment. QUASAR, Inc., (San Diego, CA) has developed a prototype dry electrode system for electroencephalography that requires minimal preparation. A comparison of the …

Quantitative Computed-Tomography Based Bone-Strength Indicators For The Identification Of Low Bone-Strength Individuals In A Clinical Environment, Bino Abel Varghese

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The aim of the current study was to develop quantitative computed-tomography (QCT)-based bone-strength indicators that highly correlate with finite-element (FE)-based strength. We perform a combined numerical-experimental study, comparing FE-predicted surface strains with strain gauge measurements, to validate the FE models of 36 long bones (humerus, radius, femur and tibia) under three-point bending and torsion. The FE models were constructed from trans-axial volumetric CT scans, and the segmented bone images were corrected for partial-volume effects. The material properties (Young's modulus for cortex, density-modulus relationship for trabecular bone and Poisson's ratio) were calibrated by minimizing the error between experiments and simulations among …

Aberrant Dna Replication At An Ectopic Chromosomal Site In Human Cells, Xiaomi Chen

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Aberrant DNA replication, including over-replication or under-replication may lead to life-threatening mutation or even cause human diseases. This thesis focused on three issues related to abnormal DNA replication in human chromosomes including: I) to define the function of DNA unwinding element (DUE) and DNA unwinding element-binding protein (DUE-B) to maintain an active c-myc replicator; II) to determine the role of trans-acting factors in defining a replication origin on human chromosomes; III) to investigate the mechanism by which hairpins affect DNA replication and instability of (CTG)n•(CAG)n trinucleotide repeat tracts in human cells.

Our laboratory previously demonstrated that both DUE and DUE-B, …

V1-Derived Renshaw Cells And Ia Inhibitory Interneurons Differentiate Early During Development, Ana Benito González

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Locomotor development is dependent on the maturation of spinal cord circuits controlling motor output, but little is known about the development of the spinal interneurons that control motoneuron activity. This study focused on the development of Renshaw cells (RCs) and Ia inhibitory interneurons (IaINs), which mediate recurrent and reciprocal inhibition, respectively, two basic inhibitory circuits for motorneuron control. Both interneurons originate from the same progenitor pool (p1) giving rise to ventral spinal embryonic interneurons denominated V1. V1-derived interneurons (V1-INs) establish local inhibitory connections with ipsilateral motoneurons and express the transcription factor engrailed-1. This characteristic permitted the generation of transgenic mice …

A Probabilistic Assessment Of Vertebral Cortical Bone Fracture Of Intraosteonal Structures, Isaac Graham Mabe

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Cortical bone is a porous structure. The presence of these pores creates the possibility of a local overstressed area that has the likelihood of premature failure. Some failure modes of the vertebral endplates, for example subsidence which occurs at rates as high as 77 percent, can be better predicted with further understanding of failure mechanisms and the ability to predict those mechanisms. A probabilistic assessment of the pore size and its contribution to the fracture toughness has not been investigated in the cortical shell of the vertebral endplates. This research develops a probabilistic model that has the ability to determine …

Anthropometric Analysis Of The Cervical Spine, Susan Hueston

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An understanding of the dimensional anatomy of the cervical spine is necessary in order to help diagnose disease, deformity, injury, and device development. Previous investigation has been completed utilizing cadavers, X-rays and other imaging techniques. This research utilized computer tomography images from the trauma registry at Miami Valley Hospital in Dayton, Ohio to complete an anthropometric study of the cervical spine. Linear mathematical models were developed to investigate the relationships present in the dimensional anatomy of the cervical spine. New measurements were completed on subjects of both Caucasian and African American descent and of both genders. An approximation of the …

Investigation Of Variability In Cognitive State Assessment Based On Electroencephalogram-Derived Features, Samantha Lokelani Crossen

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To implement adaptive aiding in modern aviation systems there is a need for accurate and reliable classification of cognitive workload. Using electroencephalogram (EEG)-derived features, it has been reported that an Artificial Neural Network (ANN) can achieve 95% or higher classification accuracy on the same day for an individual operator, but only 70% or less on a different day. To gain a further insight into this discrepancy, data from a previous study was utilized to study the classification variability. The EEG-derived features were first calculated by spectral power estimation. The variability was then analyzed by performing cognitive workload classification in which …

Selective Automatic Image Feature Detection, Aijing Wang

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To allow automatic assessment of computed tomography (CT) images of long bones, the identification of the location of regions of interest is important. The distance between the distal and proximal styloids may act as reference points for bone length; however, the locations of the distal and proximal growth plates represent further important reference features. The current methods to locate these feature positions are manual. In this project, we attempt to find these feature positions automatically.

A CT data set was split into two subsets, a development set, and a validation set. We first extracted basic information from the stack and …

Impact Of Insulin Resistance On Behavioral And Neurochemical Deficits In Db/Db Mice, Ajaykumar Narayan Sharma

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There is a high comorbidity of type-2 diabetes and neuropsychiatric disorders. However, there is paucity of preclinical research to study this phenomenon. The validity of the db/db mouse as an animal model to study type-2 diabetes and related macrovascular and microvascular complications is well established. The first part of this dissertation was designed to investigate comprehensively the db/db mouse behavior as preclinical evidence of type-2 diabetes related major neurobehavioral complications. Juvenile (5-6 weeks) and adult (10-11 weeks) db/db mice were screened for behavioral depression in forced swim test (FST), psychosis-like symptoms using pre-pulse inhibition (PPI) test, anxiety behavior employing elevated …

The Development Of Silver Nanoparticles As Antiviral Agents, John Christopher Trefry

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Silver nanoparticles (AgNPs) have received tremendous attention for their antimicrobial properties; however, many gaps in knowledge exist. To address these issues, three research objectives were examined. The first objective hypothesized AgNPs can be size selected and concentrated via tangential flow ultrafiltration. The second objective hypothesized a high-throughput method could be developed to screen nanoparticle antiviral-activity and cytotoxicity simultaneously. The third objective hypothesized AgNPs inhibit viruses by preventing viral entry.

For objective one, a tangential flow ultrafiltration scheme was tested on AgNPs synthesized via the Creighton Colloid method. AgNPs were analyzed via transmission electron microscopy. In objective two, an HIV-1 vector …

Son Is Essential For Nuclear Speckle Organization, Cell Cycle Progression And Pre-Mrna Splicing, Alok S. Sharma

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Nuclear speckles provide important spatial organization and dynamic regulation for pre-mRNA processing factors in mammalian cells. While the nuclear speckle proteome is complex, little is known at the molecular level about how these factors are organized into nuclear speckles or how alterations in the organization of these factors impacts gene expression. We have discovered a new function for a large (2564 amino acid) nuclear speckle protein called Son in maintaining the organization of pre-mRNA processing factors in nuclear speckles. Depletion of Son by RNAi causes snRNP and serine-arginine rich (SR protein) splicing factors to undergo dramatic disorganization into doughnut-shaped nuclear …

Predicting Vigilance Performance Under Transcranial Direct Current Stimulation, Nathaniel Reese Bridges

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A brain stimulation technology called transcranial direct current stimulation (tDCS) may potentially mitigate the vigilance decrement. To practically use such technology, however, a model is necessary that indicates vigilance performance, both when stimulation is being applied and not applied. To address this issue, the author developed models capable of predicting vigilance performance in real and control stimulation conditions using previous tDCS-study data. The "all possible combinations" regression method produced over 200 models, later screened to 10. The model with the best average %error (11.49 ± 0.10) used left hemispheric cerebral blood flow velocity (CBFVL) as its sole input term-accounting for …

Semi-Automated Dental Cast Analysis Software, Mathew Thomas

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Dental casts have been used extensively to study almost all aspects of the human dentition. These aspects varied from the study of tooth form and morphology, inheritance and genetics, growth and development, occlusion, arch alignment and crowding to mathematical determination of dental arch form.

The aim of this project was to develop a tool to semi-automate the measurement of dental casts that would be precise, accurate and efficient. Measurements include tooth widths, arch lengths and widths, angle of rotation and crown area for each tooth.

The task was divided into two different parts: first, the development of semi-automatic software to …

A Computational Tool For Biomolecular Structure Analysis Based On Chemical And Enzymatic Modification Of Native Proteins, Deacon John Sweeney

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Chemical and enzymatic modification of proteins is a well-established treatment technique for probing the conformational properties of these macromolecules. Investigators have recently extended the approach to probe many sites on a protein's structure in parallel manner, such that conformational properties of a target protein can be inferred. The modern approach uses mass spectrometry to quantify reactant loss and product formation. Rigorous analysis is challenging due to the high volume of mass spectrometric data that must be processed and interpreted.

An extensively interactive software suite has been developed to assist various aspects of the analytical protocol. The software offers a variety …

Cervical Spine Biomechanical Behavior And Injury, Mbulelo T. Makola

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A finite element model of the cervical spine including the C2 through C7 levels was developed in order to study the behavior of the cervical spine region. The model was validated in flexion extension, bending, and rotational load scenarios. The model was found to represent the biomechanical behavior of the cervical spine. The validated cervical spine finite element model was used to study spinal injury and disease processes. The model provided qualitative estimates of load carrying and stress distribution as well as range of motion.

The Molecular Basis Of The Interaction Between The Coxsackievirus And Adenovirus Receptor (Car) And Magi-1, Abimbola Olayinka Kolawole

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A major factor in virus entry into cells is localization and abundance of the primary receptor. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for group B coxsackievirus and many serotypes of adenovirus. In most epithelia, a seven exon isoform of CAR (CAR^Ex7) is exclusively localized at the basolateral surface where it behaves as a homophilic adhesion protein and is inaccessible for viral infection. However, in well-differentiated human airway epithelia, we recently discovered an alternatively spliced, low abundance isoform of CAR (CAR^Ex8) that is apically localized where it may initiate apical viral infection. The …