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Wright State University

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Articles 31 - 60 of 274

Full-Text Articles in Biomedical Engineering and Bioengineering

Silk Hydrogels Incorporated With Melanin, Anne Lutz Jan 2021

Silk Hydrogels Incorporated With Melanin, Anne Lutz

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Melanin is a naturally produced pigment found within the human body. Melanin is known for its ability to protect against Ultra Violet light, but also its ability to allow for mechanical protection. Making melanin a good addition to biomedical devices such as hydrogels. Silk hydrogels are weak in their load bearing capabilities but are known for their biocompatibility, biodegradability, and porosity. This makes the silk hydrogel a good material to incorporate melanin into in order to improve the mechanical properties. For the silk solution to form a solid, there must be a presence of both a catalyst and an oxidizer …


Multi-Label Classification On Locally-Linear Data: Application To Chemical Toxicity Prediction, Xiu Huan Yap Jan 2021

Multi-Label Classification On Locally-Linear Data: Application To Chemical Toxicity Prediction, Xiu Huan Yap

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Computational models may assist in identification and prioritization of large chemical libraries. Recent experimental and data curation efforts, such as from the Tox21 consortium, have contributed towards toxicological datasets of increasing numbers of chemicals and toxicity endpoints, creating a golden opportunity for the exploration of multi-label learning and deep learning approaches in this thesis. Multi-label classification (MLC) methods may improve model predictivity by accounting for label dependence. However, current measures of label dependence, such as correlation coefficient, are inappropriate for datasets with extreme class imbalance, often seen in toxicological datasets. In this thesis, we propose a novel label dependence measure …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda

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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …


Nmr Metabolomics For Optimizing Cell-Free Protein Synthesis, Angela M. Campo Jan 2021

Nmr Metabolomics For Optimizing Cell-Free Protein Synthesis, Angela M. Campo

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Cell-Free Protein Synthesis (CFPS) has been utilized by biochemists to produce a variety of chemicals and therapeutics. While CFPS has spawned research in the biochemistry and medical communities, there are still unknown issues with interlaboratory variability with the technique. This work explored the black box nature of CFPS reactions by analyzing the CFPS reactions in situ with Nuclear Magnetic Resonance (NMR) spectroscopy. Aim 1 developed the protocol for conducting NMR experiments on E. coli cell-free reactions as well as a data analysis pipeline. This was accomplished with 1H NMR, capturing metabolite changes over time. The 1D NOESY experiment proved to …


Low Frequency Oscillations Of Hemodynamic Parameters As A Novel Diagnostic Measure For Traumatic Brain Injury, Andrea Gomez Carrillo Jan 2021

Low Frequency Oscillations Of Hemodynamic Parameters As A Novel Diagnostic Measure For Traumatic Brain Injury, Andrea Gomez Carrillo

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There is a need to improve methods of monitoring patients with traumatic brain injury (TBI) in hospital settings. Current monitoring techniques and diagnosis methods are expensive, invasive, do not provide continuous measures, expose the patient to radiation, are ambiguous in the information they provide, and/or cannot be implemented at the bedside. These techniques measure imperative markers of brain function including intracranial pressure (ICP), cerebral blood flow (CBF), and oxygenation in the brain, among others. Hospitals not only require a practical method for real-time monitoring of patients at the bedside, but also meaningful metrics that characterize TBIs, since the variety of …


Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger Jan 2021

Modeling Of Excitation In Skeletal Muscle, Sabrina Kinzie Metzger

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Recent experimental findings in the Rich lab suggest there are important gaps in our understanding of muscle excitability in various disease states. To generate and test hypotheses as well as to determine whether our current understanding of various aspects of muscle excitation can fully explain experimental findings, an accurate model of muscle excitation was needed. Previous studies have modeled excitation of muscle, but in each case, important aspects were omitted. One reason for this is that little effort has been made to accurately simulate muscle action potentials. In this thesis I present progress made towards generation of a model of …


Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt Jan 2021

Alterations In Cardiac Motions Of The Failing Heart During Direct Mechanical Ventricular Actuation, Benjamin Allyn Schmitt

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Objectives: Heart failure (HF) refractory to medical management can be effectively treated with mechanical support. However, available devices are frequently associated with complications due to blood contact. Direct cardiac compression (DCC) devices augment LV systolic pump function by externally compressing the heart surface. Direct Mechanical Ventricular Actuation (DMVA) is a unique DCC method providing not only systolic but, importantly, diastolic support. However, DCC in general remains a relatively poorly understood modality. The purpose of this study was to examine DMVA’s effect on restoration of physiologic function in the failing heart. Methods: Global ischemic HF was induced with 5 mins of …


Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows Jan 2021

Augmenting Structure/Function Relationship Analysis With Deep Learning For The Classification Of Psychoactive Drug Activity At Class A G Protein-Coupled Receptors, Hannah Willow Shows

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G protein-coupled receptors (GPCRs) initiate intracellular signaling pathways via interaction with external stimuli. [1-5] Despite sharing similar structure and cellular mechanism, GPCRs participate in a uniquely broad range of physiological functions. [6] Due to the size and functional diversity of the GPCR family, these receptors are a major focus for pharmacological applications. [1,7] Current state-of-the-art pharmacology and toxicology research strategies rely on computational methods to efficiently design highly selective, low toxicity compounds. [9], [10] GPCR-targeting therapeutics are associated with low selectivity resulting in increased risk of adverse effects and toxicity. Psychoactive drugs that are active at Class A GPCRs used …


Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper Jan 2021

Als-Induced Excitability Changes In Individual Motorneurons And The Spinal Motorneuron Network In Sod1-G93a Mice At Symptom Onset, Christiana S.I. Draper

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Amyotrophic lateral sclerosis (ALS) is the most common motorneuron (MN) disease in adulthood. ALS is hallmarked by the progressive loss of MNs in the brain, brainstem, and spinal cord. Many hypotheses to explain the pathogenesis of ALS have been explored, but the exact mechanisms underlying the development of this disease remain unknown. However, abnormalities in MN excitability and glutamate excitotoxicity are the most widely studied. For decades, researchers have examined MN excitability in ALS, but the current literature is inconsistent, showing evidence of hyperexcitability, hypoexcitability, or no change in excitability of MNs in ALS. Many of these studies also focus …


Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh Jan 2021

Carbon Nanotube-Coated Scaffolds For Tissue Engineering Applications, Soham Dipakbhai Parikh

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Carbon Nanotubes (CNTs) have beneficial properties for cell scaffolding, which has translated into effective growth of bone, muscle, and cardiac cells. However, loose carbon nanotubes can cause in vivo toxicity. To reduce this risk, our team has developed biomimetic scaffolds with multiscale hierarchy where carpet-like CNT arrays are covalently bonded to larger biocompatible substrates. In this study, we have tested such scaffolds in two distinct types of biomedical applications involving glioblastoma and keratinocyte cells. The growth of glioblastoma (GBM) cells on our CNT-coated biomimetic scaffolds was evaluated to check their suitability as a potential chemotherapy-loaded implant for GBM patient treatment. …


Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda Jan 2021

Altered Skeletal Muscle Excitation-Contraction Coupling In The R6/2 Transgenic Mouse Model For Huntington's Disease, Daniel R. Miranda

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Huntington’s disease (HD) has classically been categorized as a neurodegenerative disorder. However, the expression of the disease-causing mutated huntingtin gene in skeletal muscle may contribute to the symptoms of HD, namely those that involve involuntary muscle contraction. In the R6/2 transgenic mouse model of HD, we previously observed ion channel defects that could contribute to involuntary muscle contraction. Here, in R6/2 muscle we investigated the consequence of these ion channel defects on action potentials (APs), the first step in excitation-contraction (EC) coupling. We found that the ion channel defects were associated with depolarizing the baseline membrane potential during AP trains. …


The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi Jan 2021

The Regulation Of Small Gtpase Rac1 Phosphorylation, Activation And Subcellular Localization By Δnp63Α, Amjad Ahmed Aljagthmi

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ΔNp63α, a member of the p53 family of transcription factors, plays a critical role in normal development and human disease. Loss of ΔNp63α expression is associated with increased cancer invasiveness and metastasis. The small GTPase Rac1 is a master regulator of cell motility, and increased Rac1 activity upregulates cell invasion in multiple human cancers. Increased cancer cell invasion associated with ΔNp63α knockdown and Rac1 activation suggests a novel mechanism by which ΔNp63α regulates tumor invasiveness through Rac1. Accordingly, we sought to delineate the effects of ΔNp63α on Rac1 phosphorylation, activation and subcellular localization. We identified a novel ΔNp63α/miR-320a/PKCᵧ signaling pathway …


How Do Surgeon Preferences And Technique Variances Affect Outcome?, Anastasia Axiopoulou, Caroline G. L. Cao, Katherine Lin Md, Keith Watson Md Apr 2020

How Do Surgeon Preferences And Technique Variances Affect Outcome?, Anastasia Axiopoulou, Caroline G. L. Cao, Katherine Lin Md, Keith Watson Md

Symposium of Student Research, Scholarship, and Creative Activities Materials

The goal of the research project is to create a blue-print of a robot-assisted hysterectomy procedure to support design and evaluation of technology to enhance system performance. To create this blue-print, we will conduct a task analysis, model the cognitive task flow and decision making, and develop a simulation of the hysterectomy procedure. The surgical simulation will be used as a platform to train surgeons on robotic-assisted hysterectomies, as well as to assess learning and performance. Additionally, it will be used to design and develop techniques and novel technology to support surgeons in their performance of the surgery. Current research …


Biomechanical Behavior Of A Variable Angle Locked Tibiotalocalcaneal Construct, Farah Hamandi, Gerard Simon, Richard T. Laughlin, Tarun Goswami Mar 2020

Biomechanical Behavior Of A Variable Angle Locked Tibiotalocalcaneal Construct, Farah Hamandi, Gerard Simon, Richard T. Laughlin, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

This paper examines the mechanics of the tibiotalocalcaneal construct made with a PHILOS plating system. A failed device consisting of the LCP plate and cortical, locking, and cannulated screws was used to perform the analysis. Visual, microstructure, and fractographic examinations were carried out to characterize the fracture surface topology. These examinations revealed the presence of surface scratching, inclusions, discoloration, corrosion pits, beach marks, and cleavage and striations on the fracture surface. Further examination of the material crystallography and texture revealed an interaction of S, Ni, and Mo-based inclusions that may have raised pitting susceptibility of the device made with Stainless …


Single-Pixel Camera Based Spatial Frequency Domain Imaging For Non-Contact Tissue Characterization, Alec M. Petrack Jan 2020

Single-Pixel Camera Based Spatial Frequency Domain Imaging For Non-Contact Tissue Characterization, Alec M. Petrack

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Optical imaging has demonstrated potential as a medical imaging modality for measuring tissue functionality. Recently, interest in fluorescence guided surgery has emerged from improvements in optical imaging that have allowed real-time feedback. Of the optical imaging modalities, spatial frequency domain imaging (SFDI) has gained a lot of interest. Unlike spectroscopic techniques, such as functional near infrared spectroscopy (fNIRS) and frequency domain spectroscopy that measure bulk tissue properties, SFDI quantifies tissue functionality locally and wide field making it practical for clinical applications. Unfortunately, traditional SFDI systems use multi-pixel detectors, which may not exhibit ideal spectral characteristics, have limited sensitivity, be expensive, …


Global Joint Registry: Analysis Of Revision Hip Arthroplasty Data, Alicia M. Runser Jan 2020

Global Joint Registry: Analysis Of Revision Hip Arthroplasty Data, Alicia M. Runser

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Total hip arthroplasty (THA) has become well-known as being one of the most successful procedures with much long-term positive clinical results. However, revision surgeries are still required. The four most common failure modes for THAs, “reasons for revision”, are loosening, dislocation or instability, fracture, and infection. The goal of a hip arthroplasty register is to gather information on patients that undergo a total hip arthroplasty and factors pertaining to their surgery which may affect their outcome for future years such as the reason for revision. Analysis of this data can help with the allocation of healthcare funds and the efficacy …


Observing P300 Amplitudes In Multiple Sensory Channels Using Cognitive Probing, Cody Lee Wintermute Jan 2020

Observing P300 Amplitudes In Multiple Sensory Channels Using Cognitive Probing, Cody Lee Wintermute

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High cognitive workload occurs when excessive working memory resources have been deployed to resolve sensory and cognitive processing, resulting in decremented task performance. The P300 event-related potential (ERP) component has shown sensitivity to cognitive load, and it was hypothesized that an attenuated P300 amplitude could be indicative of high cognitive load. We tested this hypothesis by having eight participants complete two continual performance tasks at increasing workload levels while simultaneously performing an oddball task, evoking P300 ERPs in either the auditory or tactile sensory channel. In our experiment, electroencephalographic recordings were collected over the parietal region to observe the P300 …


Kv2.1 Channel Clustering In The Sod1-G93a Mouse Model Of Als, Joshua Christopher Harris Jan 2020

Kv2.1 Channel Clustering In The Sod1-G93a Mouse Model Of Als, Joshua Christopher Harris

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Kv2.1 channels mediate slow-activating K+ rectifier current within the membrane of spinal motoneurons (MNs), and they are known to co-localize with other synapses and ion channels. Although Kv2.1 channels are suggested to regulate MN excitability, little research has gone into investigating its potential contribution to MN-altered excitability in Amyotrophic Lateral Sclerosis (ALS). Using the male SOD1-G93A mouse model of ALS, we examined Kv2.1 cluster area and density in lumbar MNs at four key stages of disease progression. In our experiments, MNs were separated by type via SK3 immunoreactivity in order to isolate and compare the responses of disease-resistant (slow; SK3+) …


Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis Jan 2020

Renca Macrobeads Inhibit Tumor Cell Growth Via Egfr Activation And Regulation Of Mef2 Isoform Expression, Prithy Caroline Martis

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Tumors are heterogeneous systems, whose growth is influenced by intrinsic properties of malignant cells, external systemic factors (i.e. immune, neural, endocrine, etc.), and the dynamic interactions between tumor cells and their microenvironment. Given the inherent complexity of cancers, combined with the continual evolution of tumors and the development of treatment resistance, a precision medicine approach may not provide an optimal clinical response. Exploring a new paradigm that focuses on regulating cancer as a system may not only control tumor progression but also address the extraordinary challenges of tumor heterogeneity and disease recurrence in order to improve clinical outcomes. As a …


Global Identification Of Human Modifier Genes Of Alpha-Synuclein Toxicity, Ishita Haider Jan 2020

Global Identification Of Human Modifier Genes Of Alpha-Synuclein Toxicity, Ishita Haider

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Alpha-synuclein is a small lipid binding protein abundantly expressed in the brain. Lewy body or Lewy-like pathology, primarily composed of misfolded alpha-synuclein, is a pathological feature shared by several neurodegenerative disorders, including Parkinson's disease (PD). Both missense mutations and increased copy numbers of the SNCA gene, encoding the alpha-synuclein protein, have been genetically linked to autosome dominant PD. Other genetic variations affecting the expression of the SNCA gene have been associated with sporadic PD. Although the physiological function of alpha-synuclein is not well understood, its localization to plasma and vesicular membranes at the presynaptic terminals suggests a role in neurotransmission. …


Visual Sampling With The Eeg Alpha Oscillation, Kevin Eugene Alexander Jan 2020

Visual Sampling With The Eeg Alpha Oscillation, Kevin Eugene Alexander

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The posterior alpha rhythm, seen in human electroencephalograms (EEG), is posited to originate from cycling inhibitory/excitatory states of visual relay cells in the thalamus, which could result in discrete sampling of visual information. Here, we tested this hypothesis by presenting light flashes at perceptual threshold intensity through closed eyelids to 20 participants during times of spontaneous alpha oscillations. Alpha phase and amplitude were calculated relative to each individual’s retina-to-V1 conduction delay, estimated by the individuals’ C1 visual-evoked potential latency. Our results show that an additional 20.96% of stimuli are observed when afferenting at V1 during an alpha wave trough (272.41°) …


Ultraviolet-B Radiation Induces Release Of Bioactive Microvesicle Particles In Keratinocytes Via Platelet-Activating Factor And Acid Sphingomyelinase, Langni Liu Jan 2020

Ultraviolet-B Radiation Induces Release Of Bioactive Microvesicle Particles In Keratinocytes Via Platelet-Activating Factor And Acid Sphingomyelinase, Langni Liu

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Ultraviolet-B (UV-B) radiation is one of the most common environmental factors and is known to induce the production of bioactive agents that cause several diseases including skin cancer. UVB exposure stimulates the production of a phospholipid activator, platelet-activating factor (PAF), and its analogs in keratinocytes that activate the PAF receptor (PAF-R) resulting in acute inflammatory and delayed systematic immunosuppressive effects. However, as UVB only penetrates into the skin epidermal layer, the detailed mechanisms of how UVB exerts systematic effects remains unclear. Previously we found that UVB induces keratinocytes to release large numbers of microvesicle particles (MVPs). These small membrane-bound particles …


Investigation Of Retrieved Cardiac Devices, Anmar Salih, Iosif Papadakis Ktistakis, Spyridon Manganas, Abdul Wase, Tarun Goswami Dec 2019

Investigation Of Retrieved Cardiac Devices, Anmar Salih, Iosif Papadakis Ktistakis, Spyridon Manganas, Abdul Wase, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Damage assessment of lead and pulse generator with various exposure times is important in the development of cardiac devices. Approximately, 92.1 million patients in the US suffer from cardiovascular diseases with an estimated healthcare cost of over $300 billion and at least one million with implantable cardiac devices. These devices are complex and composed on multiple levels and present challenges while assessing the damage. However, the study on the analysis of cardiac devices may lend insight into common damage patterns and improve future cardiac devices design. The objective of this work is to perform a thorough in vivo damage assessment …


Investigation Of A Neuro-Stimulator Retrieved Posthumously, Megan Markl, Rodney J. Gutherie, Tarun Goswami Dec 2019

Investigation Of A Neuro-Stimulator Retrieved Posthumously, Megan Markl, Rodney J. Gutherie, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

A neurostimulator was investigated in this paper posthumously. Device was presented to our anatomical gift program. Investigation was multi-fold and contained visual inspection, using an optical microscope, and mechanical and electrical testing of leads and its insulator. It was concluded that the device could have been damaged during implantation, in vivo, during removal, and/or during transportation to author’s laboratories. The damage observed on the lead insulation is similar to that which can occur due to anchoring of the lead and hardening due to oxidation. Insulation stiffness was determined to be 1/10 of new insulator. The results reported here on the …


Simulation Of Skull Fracture Due To Falls, Anthony Vicini, Tarun Goswami Dec 2019

Simulation Of Skull Fracture Due To Falls, Anthony Vicini, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

This study presents novel predictive equations for von Mises stress values of bones in the frontal and lateral regions of the skull. The equations were developed based on results of a finite element model developed during this research. The model was validated for frontal and lateral loading conditions with input values mimetic to fall scenarios. Using neural network processing of the information derived from the model achieved R2 values of 0.9990 for both the stress and deflection. Based on the outcome of the fall victims, a threshold von Mises stress of 40.9 to 46.6 MPa was found to indicate skull …


Deep Brain Stimulation: Prediction Model For Volume Of Tissue Stimulated, Melissa Jones, Tarun Goswami Nov 2019

Deep Brain Stimulation: Prediction Model For Volume Of Tissue Stimulated, Melissa Jones, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

An attempt has been made to understand deep brain stimulation in humans via marketable devices that are approved by the US Food and Drug Administration. The electrode characteristics were presented to influence the volume of tissue stimulated. Experimental data were digitized and VTS data were presented a function of electrode diameter, aspect ratio, applied current, pulse duration, voltage and frequency. Amongst other trends voltage and VTS were found to exhibit a three-stage relation, where Stage II characteristics were represented by a linear equation. It is in this stage, the VTS was found to be stable and where the most effective …


Stress Shielding In Cemented Hip Implants Assessed From Computed Tomography, Bharadwaj Cheruvu, Indresh Venkatarayappa, Tarun Goswami May 2019

Stress Shielding In Cemented Hip Implants Assessed From Computed Tomography, Bharadwaj Cheruvu, Indresh Venkatarayappa, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Background: Aseptic loosening is the major cause of revisions for hip replacement. This mode of failure is often caused by stress shielding. Stress shielding in the femur occurs when some of the loads are taken by the prosthesis and shielded from going to the bone. There is little information regarding the stress shielding among cemented hip implants. Purpose: The purpose of this study is to investigate the effect of stress shielding on the proximal femur with a femoral prosthesis. Methods: A patient had undergone open reduction and internal fixation (ORIF) due to a comminuted reversed oblique fracture of the right …


Chondroitin Sulfate Hydrogels For Total Wound Care Devices, Tushar Goswami Jan 2019

Chondroitin Sulfate Hydrogels For Total Wound Care Devices, Tushar Goswami

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Chondroitin sulfate (CS) is a naturally occurring bio-polymer found in areas of high cartilage in mammals. In directed applications, such as hydrogels, CS can be used to impact keratinocyte growth cycles. In this work, CS based hydrogels were utilized to accelerate wound healing and, in conjunction with a graphene sensor, monitor wound fluid pH. The hydrogels were cast onto a graphene field effect transistor (GFET) to obtain the benefits of the hydrogel wound healing capabilities, while also utilizing the pH sensitivity of the graphene. Results showed that the hydrogel caused a fivefold increase in cell size over the course of …


Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark Jan 2019

Differential Microrna Expression In Barrett's Esophagus Correlates With Regulation Of Posterior Homeotic Genes, Reilly June Clark

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Barrett’s Esophagus (BE) is characterized by the appearance of an intestinal-like epithelium in the distal esophagus. The molecular mechanisms behind BE development are unknown. BE is often preceded by Gastroesophageal Reflux Disease (GERD) and predisposes patients to esophageal adenocarcinoma (EAC). Due to the high mortality rate associated with EAC, BE patients are continuously monitored through upper endoscopy with biopsy for progression to low grade dysplasia (LGD), high grade dysplasia, and EAC. This monitoring technique poses numerous risks, so alternative surveillance and diagnostic techniques for BE pathogenesis are continually studied. microRNA biomarkers in BE pathogenesis may provide alternative means of diagnosis …


Mitochondria-Dependent Cellular Toxicity Of Α-Synuclein Modeled In Yeast, Rajalakshmi Santhanakrishnan Jan 2019

Mitochondria-Dependent Cellular Toxicity Of Α-Synuclein Modeled In Yeast, Rajalakshmi Santhanakrishnan

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Parkinson’s disease is the second most common neurodegenerative disease. This disease is caused by the degeneration of dopaminergic neurons, leading to debilitating motor symptoms and early mortality. The protein α-synuclein (α-syn), encoded by SNCA, misfolds and forms inclusions in Parkinson’s disease brains. When α-syn is overexpressed in yeast, it causes cellular toxicity and an increased number of aggregates, recapitulating the toxic phenotypes observed in humans and animal models. Yeast models are a powerful tool to perform high-throughput overexpression screening to identify modifiers of α-syn toxicity. α-syn causes mitochondrial dysfunction by inhibiting complex I and inducing mitochondrial fragmentation. Prior screening of …