Biomedical Engineering and Bioengineering Commons^™

Multiphoton Imaging Of Labeled Breast Cancer Cells To Quantify Intra And Extracellular Receptors, Sydney C. Wiggins

Biomedical Engineering Undergraduate Honors Theses

Every year 200,000 women in the United States are diagnosed with breast cancer. Of the cases diagnosed, 10% -15% are classified as triple negative breast cancer (TNBC) due to the absence of estrogen, progesterone, and HER-2/Neu receptors. This breast cancer sub-type is markedly more aggressive and twice as likely to develop in premenopausal women. TNBC is resistant to endocrine therapies and current targeted agents, making clinical need for the development of validated therapeutics for TNBC a pressing matter. To initiate drug development, the internalization of directly immunolabeled epidermal growth factor receptors (EGFR) in SK-BR-3 human breast adenocarcinoma cells was quantitated …

Exploring Oculomotor Trends In Collegiate Athletes, Brett Whorley, Julie A. Honaker

UCARE: Research Products

Collaborative efforts to improve athlete safety without significantly hindering the rules of the games aim to develop a novel system to better measure and diagnose concussions. Provided that common signs of concussions include blurred vision, distant gaze, and dizziness, the Dizziness and Balance Disorders Lab at UNL believes that the simple oculomotor exam studied in this project may be applied to this procedure. Within the broader goal to better understand the causes, signs, symptoms, and prognosis of concussions, researchers desired to further investigate the results of this oculomotor test. The aim was to identify and interpret correlations between collegiate athlete …

Modulation Of Whole Cell Currents In Human Neuroblastoma Cells Via The Hormone Aldosterone: An In Vitro Study, Harish Kumar Chittam

USF Tampa Graduate Theses and Dissertations

Ion channels play a critical role in maintaining homeostasis by moving various ions in and out of cells. The Na⁺-K⁺-2Cl^- or NKCC1 ion channel is involved in the regulation of Na⁺, K⁺, and Cl^- across cell membranes, and plays a key role in many forms of cellular physiology. In the cochlea, NKCC1 is involved in endolymph production and maintenance of the endocochlear potential. Our hypothesis is that blocking NKCC1 channels should directly impact auditory sensitivity causing hearing loss. Our lab has also shown that the hormone aldosterone (ALD) can upregulate …

Cold Atmospheric Plasma Inhibits Hiv-1 Replication In Macrophages By Targeting Both The Virus And The Cells., Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma …

Analysis Of Ca²⁺ Mobilization Of Nanosecond Pulses In Cells, Iurii Semenov

Bioelectrics Publications

Exposure to nanosecond electric pulses (nsEPs) evokes transient rise of cytosolic free Ca²⁺ concentration ([Ca²⁺]i) in the cells. We quantified the external Ca²⁺ uptake, intracellular Ca²⁺ release and uncover interplay of these processes for CHO-K1 cells upon exposure to single 60 ns pulse in the range of amplitudes from 0 to 30 kV/cm. NsEPs are distinguished by the ability to electroporate intracellular membranes. We studied how duration of nsEPs is related to efficiency of intracellular membranes electroporation comparing ability of single 300-, 60- and 10 ns pulses to recruit Ca²⁺ from endoplasmic reticulum (ER) in respect to the uptake of …

Activation Of Dna Pattern Recognition Receptors After Plasmid Electrotransfer In Melanoma Cells And Tumors, Loree Heller, Masa Bosnjak, Katarina Znidar, Maja Cemazar

Bioelectrics Publications

(First sentence) In vivo electroporation or electrotransfer, the application of controlled electric pulses, enhances delivery of plasmid DNA to a wide variety of healthy tissues as well as tumor types.

Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …

Modeling Early Stage Bone Regeneration With Biomimetic Electrospun Fibrinogen Nanofibers And Adipose-Derived Mesenchymal Stem Cells, Michael P. Francis, Yas M. Moghaddam-White, Patrick C. Sachs, Matthew J. Beckman, Stephen M. Chen, Gary L. Bowlin, Lynne W. Elmore, Shawn E. Holt

School of Medical Diagnostics & Translational Sciences Publications

The key events of the earliest stages of bone regeneration have been described in vivo although not yet modeled in an in vitro environment, where mechanistic cell-matrix-growth factor interactions can be more effectively studied. Here, we explore an early-stage bone regeneration model where the ability of electrospun fibrinogen (Fg) nanofibers to regulate osteoblastogenesis between distinct mesenchymal stem cells populations is assessed. Electrospun scaffolds of Fg, polydioxanone (PDO), and a Fg:PDO blend were seeded with adipose-derived mesenchymal stem cells (ASCs) and grown for 7-21 days in osteogenic differentiation media or control growth media. Scaffolds were analyzed weekly for histologic and molecular …

The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin

Bioelectrics Publications

The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Development Of A Vascularized, Induced Pluripotent Stem Cell-Derived Liver-Tissue Mimic For Therapeutic Applications., Venkat Madhav Ramakrishnan

Electronic Theses and Dissertations

This dissertation describes the incorporation of several technologies (stem cells, gene therapy, tissue engineering and regenerative medicine) into a single project that aims to produce a liver-tissue mimic for therapeutic applications. The liver is arguably one of the most complex organs in the body. In addition to its remarkable capacity to regenerate, it performs a host of vital functions. As a result, its impairment has widespread systemic consequences. The work described herein focused on the liver in the context of cardiovascular disease and used the heritable disorder Familial Hypercholesterolemia (FH) as a clinical disease model. As (a) the only definitive …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

The Effects Of Vagus Nerve Stimulation On Neuroinflammation In Epilepsy, Elizabeth A. St. Clair, Gabriel O Albors, Pedro Irazoqui Dr., Amy Brewster

The Summer Undergraduate Research Fellowship (SURF) Symposium

Epilepsy is a neurological disorder characterized by chronic, unexplainable seizures. Recurring epileptic seizures are associated with long-term structural damage and cognitive deficits, and can even lead to sudden, unexplainable death. Approximately 30% of epilepsy cases are not responsive to medication. Epileptic seizures often induce inflammation in the brain and may increase the frequency of future seizures, resulting in a detrimental cycle. Vagus nerve stimulation (VNS) is a non-pharmaceutical treatment method for epilepsy that has been shown to reduce inflammation in peripheral pathways. The role of VNS in the modulation of neuroinflammation has yet to be demonstrated experimentally. To explore this, …

Implantable Device For Wireless Regulation Of The Bladder Through Pelvic Nerve Stimulation, Kelsey C. Bayer, Chris Quinkert, Pedro Irazoqui

The Summer Undergraduate Research Fellowship (SURF) Symposium

Urinary incontinence (UI) is the involuntarily urination that usually effects older people or is the result of an injury. UI affects more than eleven million people and the cost of incontinence management in the United States in 2000 was $19.5 billion. Where conventional physical therapies have failed, pelvic nerve stimulation is a promising form of regulating the bladder long term. Piezoresistive pressure sensors consist of two variable resistance values and two known resistance values that are represented on a daughterboard. This unknown resistance represents the change in pressure. The filling and voiding of the bladder was characterized through acute surgeries. …

Viewing The Extracellular Matrix: An Imaging Method For Tissue Engineering, Michael Drakopoulos, Sarah Calve

The Summer Undergraduate Research Fellowship (SURF) Symposium

The field of regenerative medicine seeks to create replacement tissues and organs, both to repair deficiencies in biological function and to treat structural damage caused by injury. Scaffoldings mimicking extracellular matrix (ECM), the structure to which cells attach to form tissues, have been developed from synthetic polymers and also been prepared by decellularizing adult tissue. However, the structure of ECM undergoes significant remodeling during natural tissue repair, suggesting that ECM-replacement constructs that mirror developing tissues may promote better regeneration than those modeled on adult tissues. This work investigated the effectiveness of a method of viewing the extracellular matrix of developing …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Liver Sinusoid On A Chip: Long-Term Layered Co-Culture Of Primary Rat Hepatocytes And Endothelial Cells In Microfluidic Platforms, Young Bok (Abraham) Kang, Temitope R. Sodunke, Jason Lamontagne, Joseph Cirillo, Caroline Rajiv, Michael J. Bouchard, Moses Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

We describe the generation of microfluidic platforms for the co-culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a liver sinusoid. This paper describes a progressional study of creating such a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co-cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co-cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous …

Using The Symmetry Of False Matches To Solve The Correspondence Problem, Cherlyn J. Ng, Bart Farell

Biomedical and Chemical Engineering - All Scholarship

Veridical stereoscopic depth depends on matching corresponding image points. This requires solving the stereo correspondence problem: how are true matches distinguished from false ones? Conventional algorithms select true matches on the basis of feature detection [what do you mean by ‘feature detection’ here? Is there some more specific term?] and adherence to natural statistics. They reject false matches as noise. We propose here an alternative that uses the signals present in false matches to delineate the true solution. When visualized in a Keplerian array, binocular matches are symmetrically reflected about an axis that is a potential solution. Properties such as …

An Investigation Of The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

Implementation And Validation Of Aortic Remodeling In Hypertensive Rats, Shijia Zhao, Linxia Gu

Department of Mechanical and Materials Engineering: Faculty Publications

A computational framework was implemented and validated to better understand the hypertensive artery remodeling in both geometric dimensions and material properties. Integrating the stress-modulated remodeling equations into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both arterial thickening and stiffening effects were captured and visualized. An adaptive material remodeling strategy combined with the element birth and death techniques for the geometrical growth were implemented. The numerically predicted remodeling results in terms of the wall thickness, inner diameter, and the ratio of elastin to collagen content of the artery were compared with and fine-tuned by …

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly …

Extraction Of Intrinsic Fluorescence From Single Fiber Fluorescence Measurements On A Turbid Medium: Experimental Validation, U. A. Gamm, C. L. Hoy, F. Van Leeuwen - Van Zaane, H. J. C. M. Sterenborg, S. C. Kanick, D J. Robinson, A. Amelink

Dartmouth Scholarship

Abstract

The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence. The validity of the Monte Carlo data and semi-empirical model is …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Development Of A Multi-Purpose Automated Synthesis Module For Production Of Novel Pet Radiopharmaceuticals, I Hong Shih

Dissertations and Theses (Open Access)

Among radiopharmaceuticals of positron emission tomography (PET), ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) made from commercialized automated synthesis module is the most frequently used in tumor diagnoses. But the false positive findings, such as infectious tissues and post-operative surgical conditions, show strong uptake of ¹⁸F-FDG in PET scans which requires extra clinical procedures to confirm the results. Moreover, the false negative findings, such as low glycolytic activity tumors, reduce the accuracy of PET scans. Therefore, there will be new PET radiopharmaceuticals to redeem the defects of ¹⁸FDG-PET applications.

Current commercialized automated synthesis modules are suitable for clinical use, but …

Advances In Optics For Biotechnology, Medicine And Surgery, Maryann Fitzmaurice, Brian W. Pogue, Guillermo J. Tearney, James W. Tunnell

Dartmouth Scholarship

The guest editors introduce a Biomedical Optics Express feature issue that includes contributions from participants at the 2013 conference on Advances in Optics for Biotechnology, Medicine and Surgery XIII.

Bioerodible Calcium Sulfate Bone Grafting Substitutes With Tailored Drug Delivery Capabilities, Bryan R. Orellana

Theses and Dissertations--Biomedical Engineering

Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.

In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was …

Evaluation Of Tissue-Engineered Tendon Enthesis Polymer Constructs, Joshua A. Bundy Bs, Mary Beth Wade Phd, Hitomi Nakao Md, Phillip Mcclellan Phd, Qing Yu Phd, Robin Jacquet-Childs Ms, William J. Landis Phd

Williams Honors College, Honors Research Projects

Both scientists and clinicians have proposed tissue engineering as the future of medicine. The possibilities for tissue engineering, that is, fabrication of tissues and organs in the laboratory and their translation to patients, appear to be endless, and many believe that this new approach in medicine will result in abolishing many common ailments, injuries, and congenital defects. Injuries to a tendon enthesis, the normal tissue connection between tendon and bone, are of particular concern to clinicians because of their frequency and failure to repair as a result of surgery. While these injuries may not be life threatening, they can certainly …

A Nonrigid Registration Method For Correcting Brain Deformation Induced By Tumor Resection, Yixun Liu, Chengjun Yao, Fotis Drakopoulos, Jinsong Wu, Liangfu Zhou, Nikos Chrisochoides

Computer Science Faculty Publications

Purpose: This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point-based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model.

Methods: The method formulates the registration as a three-variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical …