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Title: TISSUE ENGINEERING THE MOTONEURON TO MUSCLE SEGMENT OF THE STRETCH REFLEX ARC CIRCUIT UTILIZING MICRO-FABRICATION, INTERFACE DESIGN AND DEFINED MEDIUM FORMULATION.
Creator: DAS, MAINAK, Hickman, James, University of Central Florida
Abstract / Description: The stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its...
Show moreThe stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its original length so as to prevent any kind of injury. It performs this compensation process using a simple negative feed back circuit called the stretch reflex arc. Any form of stretch in a muscle activates the stretch sensors (muscle spindle/ intrafusal fiber) lying deep in each muscle. After the stretch sensors get activated, it sends a train of signals to the spinal cord through the sensory neurons. The sensory neurons relay this information to the motoneuron. The motoneuron performs the necessary information processing and sends the message to the extrafusal fibers so as to compensate for the sudden stretch action. The motoneuron conveys this message to the extrafusal fibers by communicating through the special synaptic junctions called neuromuscular junctions. Based on this information, the extrafusal fibers act accordingly so as to counter the effect of sudden stretch. This is also called the monosynaptic stretch reflex that involves a single synapse between a sensory neuron and a motoneuron. To date studying these stretch reflex circuits is only feasible in animal models. Almost no effort has been made to tissue engineer such circuits for a better understanding of the complex development and repair processes of the stretch reflex circuit formation. The long-term goal of this research is to tissue engineer a cellular prototype of the entire stretch reflex circuit. The specific theme of this dissertation research was to tissue engineer the motoneuron to muscle segment of the stretch reflex arc circuit utilizing micro-fabrication, interface design and defined medium formulations. In order to address this central theme, the following hypothesis has been proposed. The first part of the hypothesis is that microfabrication technology, interface design and defined medium formulations can be effectively combined to tissue engineer the motoneuron to muscle segment of the stretch reflex arc. The second part of the hypothesis is that different growth factors, hormones, nanoparticles, neurotransmitters and synthetic substrate can be optimally utilized to regenerate the adult mammalian spinal cord neurons so as to replace the embryonic motoneurons in the stretch reflex tissue engineered construct with adult motoneurons. In this body of work, the different tissue engineering strategies and technologies have been addressed to enable the recreation of a in vitro cellular prototype of the stretch reflex circuit with special emphasis on building the motoneuron to muscle segment of the circuit. In order to recreate the motoneuron to muscle segment of the stretch reflex arc, a successful methodology to tissue engineer skeletal muscle and motoneuron was essential. Hence the recreation of the motoneuron to muscle segment of the stretch reflex circuit was achieved in two parts. In the part 1 (Chapters 2-5), the challenges in skeletal muscle tissue engineering were examined. In part 2 (Chapters 6-7), apart from tissue engineering the motoneuron to muscle segment, the real time synaptic activity between motoneuron and muscle segment were studied using extensive video recordings. In part 3 (Chapters 8-10), an innovative attempt had been made to tissue engineer the adult mammalian spinal cord neurons so that in future this technology could utilized to replace the embryonic neurons used in the stretch reflex circuit with adult neurons. The advantage of using adult neurons is that it provides a powerful tool to study older neurons since these neurons are more prone to age related changes, neurodegenerative disorders and injuries. This study has successfully demonstrated the recreation of the motoneuron to muscle segment of the stretch reflex arc and further demonstrated the successful tissue engineering strategies to grow adult mammalian spinal cord neurons. The different cell culture technologies developed in these studies could be used as powerful tools in nerve-muscle tissue engineering, neuro-prosthetic devices and in regenerative medicine.
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Date Issued: 2008
Identifier: CFE0002501, ucf:47679
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0002501

Title: TISSUE ENGINEERED MYELINATION AND THE STRETCH REFLEX ARC SENSORY CIRCUIT: DEFINED MEDIUM FORMULATION, INTERFACE DESIGN AND MICROFABRICATION.
Creator: Rumsey, John, Hickman, James, University of Central Florida
Abstract / Description: The overall focus of this research project was to develop an in vitro tissue-engineered system that accurately reproduced the physiology of the sensory elements of the stretch reflex arc as well as engineer the myelination of neurons in the systems. In order to achieve this goal we hypothesized that myelinating culture systems, intrafusal muscle fibers and the sensory circuit of the stretch reflex arc could be bioengineered using serum-free medium formulations, growth substrate interface...
Show moreThe overall focus of this research project was to develop an in vitro tissue-engineered system that accurately reproduced the physiology of the sensory elements of the stretch reflex arc as well as engineer the myelination of neurons in the systems. In order to achieve this goal we hypothesized that myelinating culture systems, intrafusal muscle fibers and the sensory circuit of the stretch reflex arc could be bioengineered using serum-free medium formulations, growth substrate interface design and microfabrication technology. The monosynaptic stretch reflex arc is formed by a direct synapse between motoneurons and sensory neurons and is one of the fundamental circuits involved in motor control. The circuit serves as a proprioceptive feedback system, relaying information about muscle length and stretch to the central nervous system (CNS). It is composed of four elements, which are split into two circuits. The efferent or motor circuit is composed of an α-motoneuron and the extrafusal skeletal muscle fibers it innervates, while the afferent or sensory circuit is composed of a Ia sensory neuron and a muscle spindle. Structurally, the two muscular units are aligned in parallel, which plays a critical role modulating the system's performance. Functionally, the circuit acts to maintain appropriate muscle length during activities as diverse as eye movement, respiration, locomotion, fine motor control and posture maintenance. Myelination of the axons of the neuronal system is a vertebrate adaptation that enables rapid conduction of action potentials without a commensurate increase in axon diameter. In vitro neuronal systems that reproduce these effects would provide a unique modality to study factors influencing sensory neuronal deficits, neuropathic pain, myelination and diseases associated with myelination. In this dissertation, results for defined in vitro culture conditions resulting in myelination of motoneurons by Schwann cells, pattern controlled myelination of sensory neurons, intrafusal fiber formation, patterned assembly of the mechanosensory complex and integration of the complex on bio-MEMS cantilever devices. Using these systems the stretch sensitive sodium channel BNaC1 and the structural protein PICK1 localized at the sensory neuron terminals associated with the intrafusal fibers was identified as well as the Ca2+ waves associated with sensory neuron electrical activity upon intrafusal fiber stretch on MEMS cantilevers. The knowledge gained through these multi-disciplinary approaches could lead to insights for spasticity inducing diseases like Parkinson's, demyelinating diseases and spinal cord injury repair. These engineered systems also have application in high-throughput drug discovery. Furthermore, the use of biomechanical systems could lead to improved fine motor control for tissue-engineered prosthetic devices.
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Date Issued: 2009
Identifier: CFE0002904, ucf:48013
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0002904

Title: HYBRID ADULT NEURON CULTURE SYSTEMS FOR USE IN PHARMACOLOGICAL TESTING.
Creator: Edwards, Darin, Hickman, James, University of Central Florida
Abstract / Description: Neuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult...
Show moreNeuronal culture systems have many applications, such as basic research into neuronal structure, function, and connectivity as well as research into diseases, conditions, and injuries affecting the brain and its components. In vitro dissociated neuronal systems have typically been derived from embryonic brain tissue, most commonly from the hippocampus of E18 rats. This practice has been motivated by difficulties in supporting regeneration, functional recovery and long-term survival of adult neurons in vitro. The overall focus of this dissertation research was to develop a dissociated neuronal culture system from human and animal adult brain tissue, one more functionally and developmentally correlative to the mature brain. To that end, this work was divided into five interrelated topics: development of an adult in vitro neuronal culture system comprised of electrically functional, mitotically stable, developmentally mature neurons from the hippocampus of adult rats; creation of stable two-cell neuronal networks for the study of synaptic communication in vitro; coupling of electrically active adult neurons to microelectrode arrays for high-throughput data collection and analysis; identification of inadequacies in embryonic neuronal culture systems and proving that adult neuronal culture systems were not deficient in similar areas; augmentation of the rat hippocampal culture system to allow for the culture and maintenance of electrically active human neurons for months in vitro. The overall hypothesis for this dissertation project was that tissue engineered in vitro systems comprised of neurons dissociated from mature adult brain tissue could be developed using microfabrication, defined medium formulations, optimized culture and maintenance parameters, and cell-cycle control. Mature differentiated glutamatergic neurons were extracted from hippocampal brain tissue and processed to purify neurons and remove tissue debris. Terminally differentiated rat hippocampal neurons recovered in vitro and displayed mature neuronal morphology. Extracellular glutamate in the culture medium promoted neuronal recovery of electrical function and activity. After recovery, essential growth factors in the culture medium caused adult neurons to reenter the cell cycle and divide multiple times. Only after reaching confluence did some neurons stop dividing. Strategies for inhibition of neuronal mitotic division were investigated, and manipulation of the cdk5 pathway was ultimately found to prevent division in vitro. Prevention of mitotic division as well as optimization of culture and maintenance parameters resulted in a neuronal culture system derived from adult rats in which the neuronal morphology, cytoskeleton and surface protein expression patterns, and electrical activity closely mirrored mature, terminally differentiated adult neurons in vivo. Improvements were also made to the growth surfaces on which neurons attached, regenerated, and survived long-term. Culture surfaces, in this case glass cover slips, were modified with the chemical substrate N-1 [3-(trimethoxysilyl) propyl]-diethylenetriamine (DETA) to create a covalently modified interface with exposed cell-adhesive triamine groups. DETA chemical surfaces were also further modified to create high-resolution patterns, useful in creating engineered two-cell networks of adult hippocampal neurons. Adult hippocampal neurons were also coupled to microelectrode array systems (MEAs) and recovered functionally, fired spontaneously, and reacted to synaptic antagonists in a manner consistent to adult neurons in vivo. Last, neurons from the brains of deceased Alzheimer's disease (AD) patients and from brain tissue excised during surgery for Parkinson's disease (PD), Essential Tremor (ET), and brain tumor were isolated and cultured, with these neurons morphological regenerating and electrically recovering in vitro.
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Date Issued: 2011
Identifier: CFE0004045, ucf:49127
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004045

Title: ESTABLISHING DEGRADATION RATES AND SERVICE LIFETIME OF PHOTOVOLTAIC SYSTEMS.
Creator: Leyte-Vidal, Albert, Hickman, James, University of Central Florida
Abstract / Description: As fossil fuel sources continue to diminish, oil prices continue to increase, and global warming and CO2 emissions keep impacting the environment, it has been necessary to shift energy consumption and generation to a different path. Solar energy has proven to be one of the most promising sources of renewable energy because it is environmentally friendly, available anywhere in the world, and cost competitive. For photovoltaic (PV) system engineers, designing a PV system is not an easy task....
Show moreAs fossil fuel sources continue to diminish, oil prices continue to increase, and global warming and CO2 emissions keep impacting the environment, it has been necessary to shift energy consumption and generation to a different path. Solar energy has proven to be one of the most promising sources of renewable energy because it is environmentally friendly, available anywhere in the world, and cost competitive. For photovoltaic (PV) system engineers, designing a PV system is not an easy task. Research demonstrates that different PV technologies behave differently under certain conditions; therefore energy production varies not only with capacity of the system but also with the type of module. For years, researchers have also studied how these different technologies perform for long periods of time, when exposed out in the field. In this study, data collected by the Florida Solar Energy Center for periods of over four years was analyzed using two techniques, widely accepted by researchers and industry, to evaluate the long‐term performance of five systems. The performance ratio analysis normalizes system capacity and enables the comparison of performance between multiple systems. In PVUSA Regression analysis, regression coefficients are calculated which correspond to the effect of irradiance, wind speed, and ambient temperature, and these coefficients are then used to calculate power at a predetermined set of conditions. This study allows manufacturers to address the difficulties found on system lifetime when their modules are installed out on the field. Also allows for the further development and improvement of the different PV technologies already commercially available.
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Date Issued: 2010
Identifier: CFE0003326, ucf:48483
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003326

Title: GLIAL DIFFERENTIATION OF HUMAN UMBILICAL STEM CELLS IN 2D AND 3D ENVIRONMENTS.
Creator: Davis, Hedvika, Hickman, James, University of Central Florida
Abstract / Description: During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress...
Show moreDuring differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth factors in the differentiation medium. In co-culture, physical cues provided by axons were essential for complete differentiation of both astrocytes and oligodendrocytes. This study presents a novel method of obtaining glia from human MLPCs that could eliminate many of the difficulties associated with their differentiation from embryonic stem cells. In addition, it reveals the complex interplay between physical cues and biomolecules on stem cell differentiation.
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Date Issued: 2011
Identifier: CFE0003570, ucf:48894
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003570

Title: PATTERNED CELL CULTURES FOR HIGH THROUGHPUT STUDIES OF CELL ELECTROPHYSIOLOGY AND DRUG SCREENING APPLICATIONS.
Creator: Natarajan, Anupama, Hickman, James, University of Central Florida
Abstract / Description: Over the last decade, the field of tissue and bio-engineering has seen an increase in the development of in vitro high-throughput hybrid systems that can be used to understand cell function and behavior at the cellular and tissue levels. These tools would have a wide array of applications including for implants, drug discovery, and toxicology, as well as for studying cell developmental behavior and as disease models. Currently, there are a limited number of efficient, functional drug...
Show moreOver the last decade, the field of tissue and bio-engineering has seen an increase in the development of in vitro high-throughput hybrid systems that can be used to understand cell function and behavior at the cellular and tissue levels. These tools would have a wide array of applications including for implants, drug discovery, and toxicology, as well as for studying cell developmental behavior and as disease models. Currently, there are a limited number of efficient, functional drug screening assays in the pharmacology industry and studies of cell-surface interactions are complicated and invasive. Most cell physiology studies are performed using conventional patch-clamp techniques or random networks cultured on silicon devices such as Microelectrode Arrays (MEAs) and Field Effect transistors (FETs). The objective of this study was to develop high-throughput in vitro platforms that could be used to analyze cell function and their response to various stimuli. Our hypothesis was that by utilizing surface modification to provide external guidance cues for various cell types and by controlling the cell environment in terms of culture conditions, we could develop an in vitro hybrid platform for sensing and testing applications. Such a system would not only give information regarding the surface effects on the growth and behavior of cells for implant development applications, but also allow for the study of vital cell physiology parameters like conduction velocity in cardiomyocytes and synaptic plasticity in neuronal networks. This study outlines the development of these in vitro high throughput systems that have varied applications ranging from tissue engineering to drug development. We have developed a simple and relatively high-throughput method in order to test the physiological effects of varying chemical environments on rat embryonic cardiac myocytes in order to model the degradation effects of polymer scaffolds. Our results, using our simple test system, are in agreement with earlier observations that utilized a complex 3D biodegradable scaffold. Thus, surface functionalization with self-assembled monolayers combined with histological/physiological testing could be a relatively high throughput method for biocompatibility studies and for the optimization of the material/tissue interface in tissue engineering. Traditional multielectrode extracellular recording methods were combined with surface patterning of cardiac myocyte monolayers to enhance the information content of the method; for example, to enable the measurement of conduction velocity, refractory period after action potentials or to create a functional reentry model. Two drugs, 1-Heptanol, a gap junction blocker, and Sparfloxacin, a fluoroquinone antibiotic, were tested in this system. 1-Heptanol administration resulted in a marked reduction in conduction velocity, whereas Sparfloxacin caused rapid, irregular and unsynchronized activity, indicating fibrillation. As shown in these experiments, the patterning of cardiac myocyte monolayers increased the information content of traditional multielectrode measurements. Patterning techniques with self-assembled monolayers on microelectrode arrays were also used to study the physiological properties of hippocampal networks with functional uni-directional connectivity, developed to study the mono-synaptic connections found in the dentate gyrus. Results indicate that changes in synaptic connectivity and strength were chemically induced in these patterned hippocampal networks. This method is currently being used for studying long term potentiation at the cellular level. For this purpose, two cell patterns were optimized for cell migration onto the pattern as demonstrated by time lapse studies, and for supporting the best pattern formation and cell survival on these networks. The networks formed mature interconnected spiking neurons. In conclusion, this study demonstrates the development and testing of in vitro high-throughput systems that have applications in drug development, understanding disease models and tissue engineering. It can be further developed for use with human cells to have a more predictive value than existing complex, expensive and time consuming methods.
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Date Issued: 2010
Identifier: CFE0003384, ucf:48437
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003384

Title: STUDY OF THE INTERACTIONS OF PROTEINS, CELLS AND TISSUE WITH BIOMATERIALS.
Creator: Bhalkikar, Abhijeet, Hickman, James, University of Central Florida
Abstract / Description: Bioengineering is the application of engineering principles to address challenges in the fields of biology and medicine. Biomaterials play a major role in bioengineering. This work employs a three level approach to study the various interactions of biomaterials with proteins, cells and tissue in-vitro. In the first study, we qualitatively and quantitatively analyzed the process of protein adsorption of two enzymes to two different surface chemistries, which are commonly used in the field. In...
Show moreBioengineering is the application of engineering principles to address challenges in the fields of biology and medicine. Biomaterials play a major role in bioengineering. This work employs a three level approach to study the various interactions of biomaterials with proteins, cells and tissue in-vitro. In the first study, we qualitatively and quantitatively analyzed the process of protein adsorption of two enzymes to two different surface chemistries, which are commonly used in the field. In the second study, we attempted to engineer a tissue construct to build a biocompatible interface between a titanium substrate and human skin. In the third study, an in-vitro model of the motoneuron-muscle part of the stretch reflex arc circuit was developed. Using a novel silicon based micro-cantilever device, muscle contraction dynamics were measured and have shown the presence of a functional neuro-muscular junction (NMJ). These studies have potential applications in the rational design of biomaterials used for biosensors and other implantable devices, in the development of a functional prosthesis and as a high-throughput drug-screening platform to study various neuro-muscular disorders.
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Date Issued: 2010
Identifier: CFE0003347, ucf:48433
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0003347

Title: APPLICATION OF ALKYLSILANE SELF-ASSEMBLED MONOLAYERS FOR CELLPATTERNING AND DEVELOPMENT OF BIOLOCIAL MICROELECTROMECHANICALSYSTEMS.
Creator: Wilson, Kerry, Hickman, James, University of Central Florida
Abstract / Description: Advances in microfabrication and surface chemistry techniques have provided a new paradigm for the creation of in vitro systems for studying problems in biology and medicine in ways that were previously not practical. The ability to create devices with micro- to nano-scale dimensions provides the opportunity to non-invasively interrogate and monitor biological cells and tissue in large arrays and in a high-throughput manner. These systems hold the potential to, in time, revolutionize the way...
Show moreAdvances in microfabrication and surface chemistry techniques have provided a new paradigm for the creation of in vitro systems for studying problems in biology and medicine in ways that were previously not practical. The ability to create devices with micro- to nano-scale dimensions provides the opportunity to non-invasively interrogate and monitor biological cells and tissue in large arrays and in a high-throughput manner. These systems hold the potential to, in time, revolutionize the way problems in biology and medicine are studied in the form of point-of-care devices, lab-on-chip devices, and biological microelectromechanical systems (BioMEMS). With new in vitro models, it will be possible to reduce the overall cost of medical and biological research by performing high-throughput experiments while maintaining control over a wide variety of experimental variables. A critical aspect of developing these sorts of systems, however, is controlling the device/tissue interface. The surface chemistry of cell-biomaterial and protein-biomaterial interactions is critical for long-term efficacy and function of such devices. The work presented here is focused on the application of surface and analytical chemistry techniques for better understanding the interface of biological elements with silica substrates and the development a novel Bio-MEMS device for studying muscle and neuromuscular biology. A novel surface patterning technique based on the use of a polyethylene glycol (PEG) silane self-assembled monolayer (SAM) as a cytophobic surface and the amine-terminated silane diethyeletriamine (DETA) as a cytophilic surface was developed for patterning a variety of cell types (e.g. skeletal muscle, and neural cells) over long periods of time (over 40 days) with high fidelity to the patterns. This method was then used to pattern embryonic rat skeletal muscle and motor neurons onto microfabricated silicon cantilevers creating a novel biological microelectromechanical system (BioMEMS) for studying muscle and the neuromuscular junction. This device was then used to study the effect of exogenously applied substances such as growth factors and toxins. Furthermore, a whispering-gallery mode (WGM) biosensor was developed for measuring the adsorption of various proteins onto glass microspheres coated with selected silane SAMS commonly used in BioMEMS system. With this biosensor it was possible to measure the kinetics of protein adsorption onto alkylsilane SAMS, in a real-time and label-free manner.
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Date Issued: 2009
Identifier: CFE0002631, ucf:48210
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0002631

Title: Cell Printing: An Effective Advancement for the Creation of um Size Patterns for Integration into Microfluidic BioMEMs Devices.
Creator: Aubin, Megan, Hickman, James, Coffey, Kevin, Lambert, Stephen, University of Central Florida
Abstract / Description: The Body-on-a-Chip (BoaC) is a microfluidic BioMEMs project that aims to replicate major organs of the human body on a chip, providing an in vitro drug testing platform without the need to resort to animal model testing. Using a human model also provides significantly more accurate drug response data, and may even open the door to personalized drug treatments. Microelectrode arrays integrated with human neuronal or human cardiac cells that are positioned on the electrodes are essential...
Show moreThe Body-on-a-Chip (BoaC) is a microfluidic BioMEMs project that aims to replicate major organs of the human body on a chip, providing an in vitro drug testing platform without the need to resort to animal model testing. Using a human model also provides significantly more accurate drug response data, and may even open the door to personalized drug treatments. Microelectrode arrays integrated with human neuronal or human cardiac cells that are positioned on the electrodes are essential components for BoaC systems. Fabricating these substrates relies heavily on chemically patterned surfaces to control the orientation and growth of the cells. Currently, cells are plated by hand onto the surface of the chemically patterned microelectrode arrays. The cells that land on the cytophobic 2-[Methoxy(Polyethyleneoxy)6-9Propyl]trimethoxysilane (PEG) coating die and detach from the surface, while the cells that land on the cytophilic diethylenetriamine (DETA) coating survive and attach to the surface exhibiting normal physiology and function. The current technique wastes a significant amount of cells, some of which are extremely expensive, and is labor intensive. Cell printing, the process of dispensing cells through a 3D printer, makes it possible to pinpoint the placement of cells onto the microelectrodes, drastically reducing the number of cells utilized. Scaled-up manufacturing is also possible due to the automation capabilities provided by printing. In this work, the specific conditions for printing each cell type is unique, the printing of human motoneurons, human sensory neurons and human cardiac cells was investigated. The viability and functionality of the printed cells are demonstrated by phase images, immunostaining and electrical signal recordings. The superior resolution of cell printing was then taken one step further by successfully printing two different cell types in close proximity to encourage controlled innervation and communication.
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Date Issued: 2017
Identifier: CFE0007390, ucf:52074
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007390

Title: Reactive sputter deposition of lithium phosphorus oxynitride thin films, a Li battery solid state electrolyte.
Creator: Mani, Prabhu Doss, Coffey, Kevin, Heinrich, Helge, Hickman, James, Sundaram, Kalpathy, University of Central Florida
Abstract / Description: Lithium phosphorus oxy-nitride (LiPON) thin films are widely studied and used as a thin film electrolyte for lithium ion battery applications. LiPON thin films may be prepared by many techniques, but RF sputter deposition is most frequently used and was investigated in this dissertation, in spite of its low deposition rate, because of it offers more reliable and controllable processing. This dissertation includes the methodologies of sputter deposition and materials characterization of the...
Show moreLithium phosphorus oxy-nitride (LiPON) thin films are widely studied and used as a thin film electrolyte for lithium ion battery applications. LiPON thin films may be prepared by many techniques, but RF sputter deposition is most frequently used and was investigated in this dissertation, in spite of its low deposition rate, because of it offers more reliable and controllable processing. This dissertation includes the methodologies of sputter deposition and materials characterization of the LiPON thin film electrolytes.The LiPON thin films were deposited under varying conditions of process gas, substrate bias, and deposition temperature. To understand the variations in ionic conductivity observed, the films were extensively characterized to examine structural and compositional differences, including examination by x-ray photoelectron spectroscopy (XPS), inductively coupled plasma optical emission spectroscopy (ICP/OES), and spectroscopic ellipsometry. In addition, film density, and the intrinsic stress of the deposited films were also studied.The highest ionic conductivity of 9.8 x 10-6 S/cm was obtained at elevated deposition temperature and is correlated to a reduced density of defects, as indicated from the optical characterization.
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Date Issued: 2015
Identifier: CFE0005835, ucf:50929
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005835

Title: Characterization of a Spiking Neuron Model via a Linear Approach.
Creator: Jabalameli, Amirhossein, Behal, Aman, Hickman, James, Haralambous, Michael, University of Central Florida
Abstract / Description: In the past decade, characterizing spiking neuron models has been extensively researched as anessential issue in computational neuroscience. In this thesis, we examine the estimation problemof two different neuron models. In Chapter 2, We propose a modified Izhikevich model withan adaptive threshold. In our two-stage estimation approach, a linear least squares method anda linear model of the threshold are derived to predict the location of neuronal spikes. However,desired results are not...
Show moreIn the past decade, characterizing spiking neuron models has been extensively researched as anessential issue in computational neuroscience. In this thesis, we examine the estimation problemof two different neuron models. In Chapter 2, We propose a modified Izhikevich model withan adaptive threshold. In our two-stage estimation approach, a linear least squares method anda linear model of the threshold are derived to predict the location of neuronal spikes. However,desired results are not obtained and the predicted model is unsuccessful in duplicating the spikelocations. Chapter 3 is focused on the parameter estimation problem of a multi-timescale adaptivethreshold (MAT) neuronal model. Using the dynamics of a non-resetting leaky integrator equippedwith an adaptive threshold, a constrained iterative linear least squares method is implemented tofit the model to the reference data. Through manipulation of the system dynamics, the thresholdvoltage can be obtained as a realizable model that is linear in the unknown parameters. This linearlyparametrized realizable model is then utilized inside a prediction error based framework to identifythe threshold parameters with the purpose of predicting single neuron precise firing times. Thisestimation scheme is evaluated using both synthetic data obtained from an exact model as well asthe experimental data obtained from in vitro rat somatosensory cortical neurons. Results show theability of this approach to fit the MAT model to different types of reference data.
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Date Issued: 2015
Identifier: CFE0005958, ucf:50803
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005958

Title: Development of human and rodent based in vitro systems toward better translation of bench to bedside in vivo results.
Creator: Berry, Bonnie, Hickman, James, Khaled, Annette, Lambert, Stephen, Sugaya, Kiminobu, University of Central Florida
Abstract / Description: Prospective medicinal compounds progress through multiple testing phases before becoming licensed drugs. Testing of novel compounds includes a preclinical phase where the potential therapeutic is tested in vitro and/or in animal models in vivo to predict its potential efficacy and/or toxicity in humans. The failure of preclinical models to accurately predict human drug responses can lead to potentially dangerous compounds being administered to humans, or potentially beneficial compounds being...
Show moreProspective medicinal compounds progress through multiple testing phases before becoming licensed drugs. Testing of novel compounds includes a preclinical phase where the potential therapeutic is tested in vitro and/or in animal models in vivo to predict its potential efficacy and/or toxicity in humans. The failure of preclinical models to accurately predict human drug responses can lead to potentially dangerous compounds being administered to humans, or potentially beneficial compounds being kept in development abeyance. Moreover, inappropriate choice in model organism for studying disease states may result in pushing forward inappropriate drug targets and/or compounds and wasting valuable time and resources in producing much-needed medications. In this dissertation, models for basic science research and drug testing are investigated with the intention of improving current preclinical models in order to drive drugs to market faster and more efficiently. We found that embryonic rat hippocampal neurons, commonly used to study neurodegenerative disease mechanisms in vitro, take 3-4 weeks to achieve similar, critical ion-channel expression profiles as seen in adult rat hippocampal cultures. We also characterized a newly-available commercial cell line of human induced pluripotent stem cell-derived neurons for their applicability in long-term studies, and used them to develop a more pathologically relevant model of early Alzheimer's Disease in vitro. Finally, we attempted to create an engineered, layered neural network of human neurons to study drug responses and synaptic mechanisms. Utilization of the results and methods described herein will help push forward the development of better model systems for translation of laboratory research to successful clinical human drug trials.
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Date Issued: 2015
Identifier: CFE0006261, ucf:51031
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006261

Title: Development of a Functional In Vitro 3D Model of the Peripheral Nerve.
Creator: Anderson, Wesley, Lambert, Stephen, Hickman, James, Fernandez-Valle, Cristina, Willenberg, Bradley, University of Central Florida
Abstract / Description: Peripheral neuropathies, affect approximately 20 million people in the United States and are often a complication of conditions such as diabetes that can result in amputation of affected areas such as the feet and toes. In vitro methodologies to facilitate the understanding and treatment of these disorders often lack the cellular and functional complexity required to accurately model peripheral neuropathies. In particular, they are often 2-D and functional readouts, such as electrical...
Show morePeripheral neuropathies, affect approximately 20 million people in the United States and are often a complication of conditions such as diabetes that can result in amputation of affected areas such as the feet and toes. In vitro methodologies to facilitate the understanding and treatment of these disorders often lack the cellular and functional complexity required to accurately model peripheral neuropathies. In particular, they are often 2-D and functional readouts, such as electrical activity, are limited to cell bodies thereby limiting the understanding of axonopathy which often characterizes these disorders. We have developed a functional 3-D model of peripheral nerves using a capillary alginate gel (Capgel(TM)), as a scaffold. We hypothesize that: 1) The unique microcapillary structure of Capgel(TM) allows for the modeling of the 3-D microstructure of the peripheral nerve, and 2) That axon bundling in the capillary allows for the detection of axonal electrical activity. In our initial studies, we demonstrate that culturing embryonic dorsal root ganglia (DRG) within the Capgel(TM) environment allows for the separation of cell bodies from axons and recreates many of the features of an in vivo peripheral nerve fascicle including myelinated axons and the formation of a rudimentary perineurium. To develop functionality for this model we have integrated the DRG Capgel(TM) culture with a microelectrode array to examine spontaneous activity in axon bundles, which we find demonstrates superiority to other widely used 2-D models of the same tissue. Furthermore, by analyzing the activity on individual electrodes, we were able to record action potentials from multiple axons within the same bundle indicating a functional complexity comparable to that observed in fascicles in vivo. This 3D model of the peripheral nerve can be used to study the functional complexities of peripheral neuropathies and nerve regeneration as well as being utilized in the development of novel therapeutics.
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Date Issued: 2018
Identifier: CFE0007150, ucf:52303
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007150

Title: Modeling Transport and Protein Adsorption in Microfluidic Systems.
Creator: Finch, Craig, Hickman, James, Kincaid, John, Lin, Kuo-Chi, Behal, Aman, Cho, Hyoung, University of Central Florida
Abstract / Description: This work describes theoretical advances in the modeling and simulation of microfluidic systems and demonstrates the practical application of those techniques. A new multi-scale model of the adsorption of hard spheres was formulated to bridge the gap between simulations of discrete particles and continuum fluid dynamics. A whispering gallery mode (WGM) biosensor was constructed and used to measure the kinetics of adsorption for two types of proteins on four different surfaces. Computational...
Show moreThis work describes theoretical advances in the modeling and simulation of microfluidic systems and demonstrates the practical application of those techniques. A new multi-scale model of the adsorption of hard spheres was formulated to bridge the gap between simulations of discrete particles and continuum fluid dynamics. A whispering gallery mode (WGM) biosensor was constructed and used to measure the kinetics of adsorption for two types of proteins on four different surfaces. Computational fluid dynamics was used to analyze the transport of proteins in the flow cell of the biosensor. Kinetic models of protein adsorption that take transport limitations into account were fitted to the experimental data and used to draw conclusions about the mechanisms of adsorption. Transport simulations were then applied to the practical problem of optimizing the design of a microfluidic bioreactor to enable (")plugs(") of fluid to flow from one chamber to the next with minimal dispersion. Experiments were used to validate the transport simulations. The combination of quantitative modeling and simulation and experiments led to results that could not have been achieved using either approach by itself. Simulation tools that accurately predict transport and protein adsorption will enable the rational design of microfluidic devices for biomedical applications.
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Date Issued: 2011
Identifier: CFE0004474, ucf:49313
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004474

Title: Photoactivatable Organic and Inorganic Nanoparticles in Cancer Therapeutics and Biosensing.
Creator: Mathew, Mona, Gesquiere, Andre, Hickman, James, Ye, Jingdong, Campiglia, Andres, Schoenfeld, Winston, University of Central Florida
Abstract / Description: In photodynamic therapy a photosensitizer drug is administered and is irradiated with light. Upon absorption of light the photosensitizer goes into its triplet state and transfers energy or an electron to oxygen to form reactive oxygen species (ROS). These ROS react with biomolecules in cells leading to cell damage and cell death. PDT has interested many researchers because of its non-invasiveness as compared to surgery, it leaves little to no scars, it is time and cost effective, it has...
Show moreIn photodynamic therapy a photosensitizer drug is administered and is irradiated with light. Upon absorption of light the photosensitizer goes into its triplet state and transfers energy or an electron to oxygen to form reactive oxygen species (ROS). These ROS react with biomolecules in cells leading to cell damage and cell death. PDT has interested many researchers because of its non-invasiveness as compared to surgery, it leaves little to no scars, it is time and cost effective, it has potential for targeted treatment, and can be repeated as needed. Different photosensitizers such as porphyrines, chlorophylls, and dyes have been used in PDT to treat various cancers, skin diseases, aging and sun-damaged skin. These second generation sensitizers have yielded reduced skin sensitivity and improved extinction coefficients (up to ~ 105 L mol-1 cm-1). While PDT based on small molecule photosensitizers has shown great promise, several problems remain unsolved. The main issues with current sensitizers are (i) hydrophobicity leading to aggregation in aqueous media resulting in reduced efficacy and potential toxicity, (ii) dark toxicity of photosensitizers, (iii) non-selectivity towards malignant tissue resulting in prolonged cutaneous photosensitivity and damage to healthy tissue, (iv) limited light absorption efficiency, and (v) a lack of understanding of where the photosensitizer ends up in the tissue. In this dissertation research program, these issues were addressed by the development of conducting polymer nanoparticles as a next generation of photosensitizers. This choice was motivated by the fact that conducting polymers have large extinction coefficients ((>) 107 L mol-1 cm-1), are able to undergo intersystem crossing to the triplet state, and have triplet energies that are close to that of oxygen. It was therefore hypothesized that such polymers could be effective at generating ROS due to the large excitation rate that can be generated. Conducting polymer nanoparticles (CPNPs) composed of the conducting polymer poly[2-methoxy-5-(2-ethylhexyl-oxy)-p-phenylenevinylene] (MEH-PPV) were fabricated and studied in-vitro for their potential in PDT application. Although not fully selective, the nanoparticles exhibited a strong bias to the cancer cells. The formation of ROS was proven in-vitro by staining of the cells with CellROX Green Reagent, after which PDT results were quantified by MTT assays. Cell mortality was observed to scale with nanoparticle dosage and light dosage. Based on these promising results the MEH-PPV nanoparticles were developed further to allow for surface functionalization, with the aim of targeting these NPs to cancer cell lines. For this work targeting of cancers that overexpress folate receptors (FR) were considered. The functionalized nanoparticles (FNPs) were studied in OVCAR3 (ovarian cancer cell line) as FR+, MIA PaCa2 (pancreatic cell line) as FR-, and A549 (lung cancer cell line) having marginal FR expression. Complete selectivity of the FNPs towards the FR+ cell line was found. Quantification of PDT results by MTS assays and flow cytometry show that PDT treatment was fully selective to the FR+ cell line (OVCAR3). No cell mortality was observed for the other cell lines studied here within experimental error. Finally, the issue of confirming and quantifying small molecule drug delivery to diseased tissue was tackled by developing quantum dot (Qdot) biosensors with the aim of achieving fluorescence reporting of intracellular small molecule/drug delivery. For fluorescence reporting prior expertise in control of the fluorescence state of Qdots was employed, where redox active ligands can place the Qdot in a quenched OFF state. Ligand attachment was accomplished by disulfide linker chemistry. This chemistry is reversible in the presence of sulfur reducing biomolecules, resulting in Qdots in a brightly fluorescent ON state. Glutathione (GSH) is such a biomolecule that is present in the intracellular environment. Experimental in-vitro data shows that this design was successfully implemented.
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Date Issued: 2014
Identifier: CFE0005839, ucf:50923
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005839

Title: A high-content multiplexed screening platform for the evaluation and manipulation of force and fatigue of adult derived skeletal muscle myotubes in defined serum-free medium.
Creator: McAleer, Christopher, Hickman, James, Ebert, Steven, Perez Figueroa, J. Manuel, Lambert, Stephen, University of Central Florida
Abstract / Description: The overall focus of this project has two parts: First, was to develop a protocol utilizing serum-free media formulations and defined plating and culture techniques to create functional in vitro myotubes derived from adult skeletal muscle satellite cells. The second was to manipulate the inherent muscle parameters such as force output and fatigue of these myotubes by employing exercise regimes or by small molecule application. The importance of serum-free medium use for in vitro cultures is...
Show moreThe overall focus of this project has two parts: First, was to develop a protocol utilizing serum-free media formulations and defined plating and culture techniques to create functional in vitro myotubes derived from adult skeletal muscle satellite cells. The second was to manipulate the inherent muscle parameters such as force output and fatigue of these myotubes by employing exercise regimes or by small molecule application. The importance of serum-free medium use for in vitro cultures is becoming increasingly important in creating functional systems that can be validated for drug testing by the Food and Drug Administration (FDA). Also, the study of age related diseases as well as the potential for (")personalized medicine(") relies on the proliferation and maturation of satellite cells from adult derived tissue. For that purpose, a serum-free medium and culture system was designed to create mature striated myotubes in culture on a defined non-biological substrate N-1[3-trimethoxysilyl propyl] diethylenetriamine (DETA). These myotubes were evaluated by morphology, muscle specific protein expression, and by muscle functionality. After the thorough characterization of the resultant myotubes the functional output of the muscle was altered utilizing chemical means (creatine supplementation and PGC-1? agonists), chronic long term stimulation, and the use of PGC-1? deficient tissue. In this thesis presentation the utility of the newly developed medium formulation to create myotubes from a variety of adult derived muscle sources will be shown. A protocol in which to exercise skeletal muscle in vitro to alter endurance was developed and employed to manipulate skeletal muscle. Finally, small molecules were tested to validate this system for drug study use. This engineered system has the potential for high-throughput screening of drugs for efficacy and drug toxicity studies as well as general biological studies on muscle fatigue.
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Date Issued: 2015
Identifier: CFE0005660, ucf:50162
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005660

Title: Action potentials as indicators of metabolic perturbations for temporal proteomic analysis.
Creator: Kolli, Aditya Reddy, Hickman, James, Clausen, Christian, Ballantyne, John, Gesquiere, Andre, Jha, Sumit, University of Central Florida
Abstract / Description: The single largest cause of compound attrition during drug development is due to inadequate tools capable of predicting and identifying protein interactions. Several tools have been developed to explore how a compound interferes with specific pathways. However, these tools lack the potential to chronically monitor the time dependent temporal changes in complex biochemical networks, thus limiting our ability to identify possible secondary signaling pathways that could lead to potential...
Show moreThe single largest cause of compound attrition during drug development is due to inadequate tools capable of predicting and identifying protein interactions. Several tools have been developed to explore how a compound interferes with specific pathways. However, these tools lack the potential to chronically monitor the time dependent temporal changes in complex biochemical networks, thus limiting our ability to identify possible secondary signaling pathways that could lead to potential toxicity. To overcome this, we have developed an in silico neuronal-metabolic model by coupling the membrane electrical activity to intracellular biochemical pathways that would enable us to perform non-invasive temporal proteomics. This model is capable of predicting and correlating the changes in cellular signaling, metabolic networks and action potential responses to metabolic perturbation.The neuronal-metabolic model was experimentally validated by performing biochemical and electrophysiological measurements on NG108-15 cells followed by testing its prediction capabilities for pathway analysis. The model accurately predicted the changes in neuronal action potentials and the changes in intracellular biochemical pathways when exposed to metabolic perturbations. NG108-15 cells showed a large effect upon exposure to 2DG compared to cyanide and malonate as these cells have elevated glycolysis. A combinational treatment of 2DG, cyanide and malonate had a much higher and faster effect on the cells. A time-dependent change in neuronal action potentials occurred based on the inhibited pathway. We conclude that the experimentally validated in silico model accurately predicts the changes in neuronal action potential shapes and proteins activities to perturbations, and would be a powerful tool for performing proteomics facilitating drug discovery by using action potential peak shape analysis to determine pathway perturbation from an administered compound.
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Date Issued: 2014
Identifier: CFE0005822, ucf:50037
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005822

Title: Nonlinear dynamic modeling, simulation and characterization of the mesoscale neuron-electrode interface.
Creator: Thakore, Vaibhav, Hickman, James, Mucciolo, Eduardo, Rahman, Talat, Johnson, Michael, Behal, Aman, Molnar, Peter, University of Central Florida
Abstract / Description: Extracellular neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and whole-cell biosensing for drug screening and toxin detection. While the field of neuroelectronic interfacing holds great promise, the recording of high-fidelity signals from extracellular devices has long suffered from the problem of low signal-to-noise ratios and changes in signal shapes due to the presence of highly dispersive dielectric medium in the neuron...
Show moreExtracellular neuroelectronic interfacing has important applications in the fields of neural prosthetics, biological computation and whole-cell biosensing for drug screening and toxin detection. While the field of neuroelectronic interfacing holds great promise, the recording of high-fidelity signals from extracellular devices has long suffered from the problem of low signal-to-noise ratios and changes in signal shapes due to the presence of highly dispersive dielectric medium in the neuron-microelectrode cleft. This has made it difficult to correlate the extracellularly recorded signals with the intracellular signals recorded using conventional patch-clamp electrophysiology. For bringing about an improvement in the signal-to-noise ratio of the signals recorded on the extracellular microelectrodes and to explore strategies for engineering the neuron-electrode interface there exists a need to model, simulate and characterize the cell-sensor interface to better understand the mechanism of signal transduction across the interface. Efforts to date for modeling the neuron-electrode interface have primarily focused on the use of point or area contact linear equivalent circuit models for a description of the interface with an assumption of passive linearity for the dynamics of the interfacial medium in the cell-electrode cleft. In this dissertation, results are presented from a nonlinear dynamic characterization of the neuroelectronic junction based on Volterra-Wiener modeling which showed that the process of signal transduction at the interface may have nonlinear contributions from the interfacial medium. An optimization based study of linear equivalent circuit models for representing signals recorded at the neuron-electrode interface subsequently proved conclusively that the process of signal transduction across the interface is indeed nonlinear. Following this a theoretical framework for the extraction of the complex nonlinear material parameters of the interfacial medium like the dielectric permittivity, conductivity and diffusivity tensors based on dynamic nonlinear Volterra-Wiener modeling was developed. Within this framework, the use of Gaussian bandlimited white noise for nonlinear impedance spectroscopy was shown to offer considerable advantages over the use of sinusoidal inputs for nonlinear harmonic analysis currently employed in impedance characterization of nonlinear electrochemical systems. Signal transduction at the neuron-microelectrode interface is mediated by the interfacial medium confined to a thin cleft with thickness on the scale of 20-110 nm giving rise to Knudsen numbers (ratio of mean free path to characteristic system length) in the range of 0.015 and 0.003 for ionic electrodiffusion. At these Knudsen numbers, the continuum assumptions made in the use of Poisson-Nernst-Planck system of equations for modeling ionic electrodiffusion are not valid. Therefore, a lattice Boltzmann method (LBM) based multiphysics solver suitable for modeling ionic electrodiffusion at the mesoscale neuron-microelectrode interface was developed. Additionally, a molecular speed dependent relaxation time was proposed for use in the lattice Boltzmann equation. Such a relaxation time holds promise for enhancing the numerical stability of lattice Boltzmann algorithms as it helped recover a physically correct description of microscopic phenomena related to particle collisions governed by their local density on the lattice. Next, using this multiphysics solver simulations were carried out for the charge relaxation dynamics of an electrolytic nanocapacitor with the intention of ultimately employing it for a simulation of the capacitive coupling between the neuron and the planar microelectrode on a microelectrode array (MEA). Simulations of the charge relaxation dynamics for a step potential applied at t = 0 to the capacitor electrodes were carried out for varying conditions of electric double layer (EDL) overlap, solvent viscosity, electrode spacing and ratio of cation to anion diffusivity. For a large EDL overlap, an anomalous plasma-like collective behavior of oscillating ions at a frequency much lower than the plasma frequency of the electrolyte was observed and as such it appears to be purely an effect of nanoscale confinement. Results from these simulations are then discussed in the context of the dynamics of the interfacial medium in the neuron-microelectrode cleft. In conclusion, a synergistic approach to engineering the neuron-microelectrode interface is outlined through a use of the nonlinear dynamic modeling, simulation and characterization tools developed as part of this dissertation research.
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Date Issued: 2012
Identifier: CFE0004797, ucf:49718
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0004797

electrophysiology (3)	+ -
microelectrode array (3)	+ -
Alzheimer's (2)	+ -
Tissue Engineering (2)	+ -
amyloid beta (2)	+ -

body-on-a-chip (2)	+ -
myelination (2)	+ -
neuroscience (2)	+ -
surface chemistry (2)	+ -
3D environment (1)	+ -
3D model (1)	+ -
3D printing (1)	+ -
A549 (1)	+ -
Action potential (1)	+ -
BioMEMS (1)	+ -
Biomaterial (1)	+ -
Biomaterials (1)	+ -
Cancer (1)	+ -
Cardiac tissue engineering (1)	+ -
Cardiomyocytes (1)	+ -
Cell culture (1)	+ -
Cells (1)	+ -
DC-AC Inverters (1)	+ -
DETA (1)	+ -
Defined Medium (1)	+ -
Electrophysiology (1)	+ -
Energy Efficiency (1)	+ -
Exercise (1)	+ -
Florida PV (1)	+ -
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Hickman, James (18)	+ -
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Lambert, Stephen (4)	+ -
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