Biomedical Engineering and Bioengineering Commons^™

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

McKelvey School of Engineering Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on …

Radiolabeled Nanohydroxyapatite As A Platform For The Development Of New Pet Imaging Agents, Stacy Lee Queern

Arts & Sciences Electronic Theses and Dissertations

Positron emission tomography (PET) imaging utilizes drugs labeled with positron emitters to target and evaluate different biological processes occurring in the body. Tailoring medicine to the individual allows for higher quality of care with better diagnosis and treatment and is a key purpose for advancing research into developing new platforms for PET imaging agents. A PET nuclide of high interest for the development of these agents is 89Zr. This can be attributed to the long half-life of 3.27 days and low positron energy of 89Zr.

In this work, we developed a production method for 89Zr using Y sputtered coins that …

Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz

Graduate Theses and Dissertations

Biofiltration without pre-ozonation has the capability to remove natural organic matter (NOM) fractions that serve as precursors of disinfection byproducts (DBPs), which include the four regulated trihalomethanes (THMs) and dichloroacetonitrile (DCAN). Rapid small-scale column tests (RSSCTs) and Pilot Plant filters operated at empty-bed contact times (EBCTs) of 4, 8, and 16 minutes were used to evaluate the performance of nutrient-amended (free ammonia and phosphorus) biofiltration for THM and DCAN precursor removal, as measured using formation potential (FP) tests. NOM surrogates – which include dissolved organic carbon (DOC), specific ultraviolet absorbance (SUVA254) and fluorescence-PARAFAC components – were measured weekly throughout the …

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

A Discrete-Event Simulation Approach For Modeling Human Body Glucose Metabolism, Buket Aydas

Theses and Dissertations

This dissertation describes CarbMetSim (Carbohydrate Metabolism Simulator), a discrete-event simulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities. CarbMetSim implements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysis and gluconeogenesis) are accounted for by …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Polymeric Peptide Mimics For Protein Delivery, Coralie Backlund

Doctoral Dissertations

The plasma membrane is a major obstacle in the development and use of biomacromolecules for intracellular applications. Consequently, proteins with intracellular targets represent an enormous, yet under studied avenue for therapeutics. Extended research has aimed at facilitating intracellular delivery of exogenous proteins using protein transduction domains (PTDs), which allow transport of bioactive molecules into cells. Synthetic polymers, inspired by PTDs, provide a well-controlled platform to vary molecular architecture for structure activity relationship studies. Specifically, this thesis focuses on the use of ring-opening metathesis, a facile and efficient polymerization technique, through which we can vary structural parameters to optimize delivery of …

A 3d Simulation Of Leukocyte Adhesion In Blood Flow, Tai-Hsien Wu

Dissertations

It has been widely acknowledged that further understanding about the dynamics between blood cells and blood flow can help us gain more knowledge about the causes of diseases and discover more effective treatments. Examples of such dynamics include red blood cell (RBC, or erythrocyte) aggregation, white blood cell (WBC, or leukocyte) margination, and WBC extravasation. WBC extravasation is an important multiple-step process in the inflammatory response and therefore has drawn considerable attention over the past two decades. In this multiple-step process, a WBC undergoes at least four steps, including capture, rolling, firm adhesion, and transmigration, and each step is influenced …

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Fluorescent Probes And Functionalized Nanoparticles For Bioimaging: Synthesis, Photophysical Properties And Applications, Xinglei Liu

Dissertations

The development of new organic molecular probes with excellent photophysical properties and high fluorescence quantum yields is of considerable interest to many research areas including one- and two-photon fluorescence microscopy, fluorescence-based sensing methodologies, and cancer therapy. Series of organic linear-/non-linear optical molecules including squaraine derivatives, and fluorene derivatives as well as other bioconjugates are designed and synthesized during the doctoral study for the aim of ion detection (Chapter 5), photo dynamic therapy, and deep-tissue imaging (Chapter 4). These optical probes are capable of absorbing light in the near infrared (NIR) window and thus have deeper penetration and cause less photodamage …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Developing Wavefront Shaping Techniques For Focusing Through Highly Dynamic Scattering Media, Ashton Hemphill

McKelvey School of Engineering Theses & Dissertations

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit of ~1 mm in soft tissue. This greatly restricts the utility of optical diagnostic and therapeutic techniques, such as optogenetics, microsurgery, optical tweezing, and phototherapy of deep tissue, which require focused light in order to function. Wavefront shaping extends the depth at which optical focusing may be achieved by compensating for phase distortions induced by scattering, allowing for focusing through constructive interference.

However, due to physiological motion, scattering of light …

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

McKelvey School of Engineering Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for …

Developing Photoacoustic Tomography Devices For Translational Medicine And Basic Science Research, Tsz Wai Wong

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) provides volumetric images of biological tissue with scalable spatial resolutions and imaging depths, while preserving the same imaging contrast—optical absorption. Taking the advantage of its 100% sensitivity to optical absorption, PAT has been widely applied in structural, functional, and molecular imaging, with both endogenous and exogenous contrasts, at superior depths than pure optical methods. Intuitively, hemoglobin has been the most commonly studied biomolecule in PAT due to its strong absorption in the visible wavelength regime.

One of the main focuses of this dissertation is to investigate an underexplored wavelength regime—ultraviolet (UV), which allows us to image …

Design & Delivery Of Automated Winston-Lutz Test For Isocentric & Off-Axis Delivery Stability Utilizing Truebeam Developer Mode & Electronic Portal Imaging Device, Mahmoud Mohammad Yaqoub

UNLV Theses, Dissertations, Professional Papers, and Capstones

The uncertainties in treatment delivery cannot be ignored in radiation therapy. Thus, the quality assurance QA tests are very important task of the medical physicist in clinical practice. Assuring the coincidence between the mechanical isocenter of the Linear Accelerator (LINAC) and its radiation beams isocenter is one of the most important qualities need to be tested, and the Winston Lust (WL) test is the

most popular technique to perform this task, especially for the treatment modalities which need high precision in beam delivery such as the stereotactic radiosurgery/stereotactic body radiotherapy (SRS/SBRT). The linear accelerator-based SRS/SBRT is a well-established method in …

Longitudinal Tracking Of Physiological State With Electromyographic Signals., Robert Warren Stallard

Electronic Theses and Dissertations

Electrophysiological measurements have been used in recent history to classify instantaneous physiological configurations, e.g., hand gestures. This work investigates the feasibility of working with changes in physiological configurations over time (i.e., longitudinally) using a variety of algorithms from the machine learning domain. We demonstrate a high degree of classification accuracy for a binary classification problem derived from electromyography measurements before and after a 35-day bedrest. The problem difficulty is increased with a more dynamic experiment testing for changes in astronaut sensorimotor performance by taking electromyography and force plate measurements before, during, and after a jump from a small platform. A …

Sex Differences In Lower Limb Biomechanics During A Single-Leg Cut With Body Borne Load, Auralea Carylon Fain

Boise State University Theses and Dissertations

Introduction: Musculoskeletal injuries are ever-increasing in military personnel, particularly females. These musculoskeletal injuries are attributed to adaptations in lower limb biomechanics while performing routine military tasks, such as a single-leg cut, with the addition of body borne load. However, it is unknown if females and males exhibit similar lower limb biomechanics with the addition of body borne load during these tasks. This study sought to compare the lower limb biomechanical adaptations exhibited by females and males performing a single-leg cut with body borne load. Methods: Eleven females and 17 males had lower limb biomechanics quantified during a single-leg cut with …

An Area Based Fan Beam Projection Model, Richard E. Steele, Jiehua Zhu

Honors College Theses

Area based projection models for computed tomography mitigate raw data errors by treating X-Rays as beams, whereas traditional line based projection models treat an X-Ray like a line, thus generating significant error. In an existing area based fan beam projection model, a rotation matrix, Q, simulates the rotation of the emitter detector pair to reduce computational load, but this introduces approximations by using an approximated rotation matrix. We eliminate approximations by deriving an exact formula for the entries of Q. Using a rotation of axes and by considering the neighboring cells' contributions to the area, the result has formulations for …

Characterization Of Computed Tomography Radiomic Features Using Texture Phantoms, Muhammad Shafiq Ul Hassan

USF Tampa Graduate Theses and Dissertations

Radiomics treats images as quantitative data and promises to improve cancer prediction in radiology and therapy response assessment in radiation oncology. However, there are a number of fundamental problems that need to be solved in order to potentially apply radiomic features in clinic. The first basic step in computed tomography (CT) radiomic analysis is the acquisition of images using selectable image acquisition and reconstruction parameters. Radiomic features have shown large variability due to variation of these parameters. Therefore, it is important to develop methods to address these variability issues in radiomic features due to each CT parameter. To this end, …

Elastin-Like Polypeptide Fusion Tag As A Protein-Dependent Solubility Enhancer Of Cysteine-Knot Growth Factors, Tamina L. Johnson

USF Tampa Graduate Theses and Dissertations

Elastin-like peptide (ELP) fusions promote therapeutic delivery and efficacy. Recombinant proteins, like neurotrophins, lack bioavailability, have short in vivo half-lives, and require high manufacturing costs. Fusing recombinant proteins with genetically encodable ELPs will increase bioavailability, enhance in vivo solubilization, as well as provide a cost-effective method for purification without the need for chromatography. During expression of neurotrophin-ELP (N-ELP) fusions, dense water-insoluble aggregates known as inclusion bodies (IBs) are formed. Inclusion bodies are partially and misfolded proteins that usually require denaturants like Urea for solubilization. Strong denaturants arrest ELPs stimuli-responsive property and increase unwanted aggregation, making purification difficult, yet possible. The …

Characterization Of Bacteriorhodopsin And Halorhodopsin Reconstituted In Lipid Bilayer Membranes, Joel Domkam Kamwa

Graduate Theses and Dissertations

Motivated to produce electricity with photon activated ion pumps, the main purpose of this work was to characterize the photosynthetic membrane proteins bacteriorhodopsin (proton pump) and halorhodopsin (chloride pump). The proteins were re-suspended in lipid bilayers. For this work, an experimental set-up was built which included: chambers for lipid bilayer formation and characterization, lasers for ion pump activation, and an AxoPatch electrophysiology system for small photocurrent measurement. Lipid bilayer membranes were formed using mostly folding method: folding two monolayers together. The membranes were characterized by their resistance, capacitance, and generated photocurrent. Photocurrent was generated upon illumination of lipid-protein membranes with …

Identification Of Streptococcus Pyogenes Using Raman Spectroscopy, Ehsan Majidi

Wayne State University Dissertations

Despite the attention that Raman Spectroscopy has gained recently in the area of pathogen identification, the spectra analyses techniques are not well developed. In most scenarios, they rely on expert intervention to detect and assign the peaks of the spectra to specific molecular vibration. Although some investigators have used machine-learning techniques to classify pathogens, these studies are usually limited to a specific application, and the generalization of these techniques is not clear. Also, a wide range of algorithms have been developed for classification problems, however, there is less insight to applying such methods on Raman spectra. Furthermore, analyzing the Raman …

Can A Comprehensive Transition Plan To Barefoot Running Be The Solution To The Injury Epidemic In American Endurance Runners?, Michael A. Scarlett

CMC Senior Theses

Fossils belonging to the genus Homo, dating as far back as two million years ago, exhibit uniquely efficient features suggesting that early humans had evolved to become exceptional endurance runners. Although they did not have the cushion or stability-control features provided in our modern day running shoes, our early human ancestors experienced far less of the running-related injuries we experience today. The injury rate has been estimated as high as 90% annually for Americans training for a marathon and as high as 79% annually for all American endurance runners. There is an injury epidemic in conventionally shod populations that …

Developing A 3d In Vitro Model By Microfluidics, Hung-Ta Chien

Dissertations and Theses

In vitro tissue models play an important role in providing a platform that mimics the realistic tissue microenvironment for stimulating and characterizing the cellular behavior. In particular, the hydrogel-based 3D in vitro models allow the cells to grow and interact with their surroundings in all directions, thus better mimicking in vivo than their 2D counterparts. The objective of this thesis is to establish a 3D in vitro model that mimics the anatomical and functional complexity of the realistic cancer microenvironment for conveniently studying the transport coupling in porous tissue structures. We pack uniform-sized PEGDA-GelMA microgels in a microfluidic chip to …