Biomedical Engineering and Bioengineering Commons^™

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

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Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …

Identifying The Impact Of Noise On Anomaly Detection Through Functional Near-Infrared Spectroscopy (Fnirs) And Eye-Tracking, Ryan Dwight Gabbard

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Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance (ISR) operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts' decision making process. In this study the effects of different noise stimuli on analysts' performance and workload in anomaly detection were investigated by simulating a noisy work environment. Functional near infrared spectroscopy (fNIRS) was utilized to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbD) concentration changes in the prefrontal cortex (PFC), as well as behavioral measures which include eye-tracking, reaction time, and accuracy rate. It was found that HbO for some of …

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells, Jeannine Marie Crum Gregoriades

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Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na+/ K+ ATPase and the Na+/ K+/ 2Cl- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na+ and Cl- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs is controversial. Determining the direction of NKCC1- mediated fluxes is …

Sensorimotor Deficits Following Oxaliplatin Chemotherapy, Jacob Adam Vincent

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Neurotoxicity is one of the most significant side effects diminishing clinical efficacy and patient quality of life during and following chemotherapy. Oxaliplatin (OX) is a platinum based chemotherapy agent used in the treatment of colorectal cancer. Colorectal cancer currently ranks as the 4th most common cancer, and the majority of patients receive OX as a part of their adjuvant therapy. OX based adjuvant therapies significantly improve 5 year survival rates, however in many cases patients must stop treatment early because of the neurotoxic side effects. OX causes two clinically distinct forms of neurotoxicity. Acutely, within hours and for days following …

Novel Mechanisms Underlying Warm-Up And Percussion Myotonia In Myotonia Congenita, Kevin Richard Nnovak

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Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. Triggers for myotonia can occur voluntarily at the neuromuscular junction or involuntarily by striking the muscle with a reflex hammer (percussion myotonia). In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm-up and percussion myotonia and to use this information to guide development of novel therapies. To determine these underlying mechanisms, we used a drug to …

Persistent Inward Currents Play A Role In Muscle Dysfunction Seen In Myotonia Congenita, Ahmed Alaa Hawash

Browse all Theses and Dissertations

Myotonia congenita is a rare skeletal muscle channelopathy caused by a reduced chloride channel (ClC-1) current, which results in debilitating muscle hyperexcitability, prolonged contractions, and transient episodes of weakness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. My in vitro intracellular recordings from a mouse homozygous knockout of ClC-1 revealed a slow after-depolarization (AfD) that triggers myotonic action potentials. The AfD is well-explained by a tetrododoxin-sensitive and voltage-dependent Na+ persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, thus providing the first mechanistic explanation for the …

Functions Of The Apical Na+/ K+/ 2cl- Cotransporter 1 In Choroid Plexus Epithelial Cells., Jeannine Marie Crum Gregoriades

Browse all Theses and Dissertations

Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) and regulate its electrolyte composition. CPECs express both the Na⁺/ K⁺ ATPase and the Na⁺/ K⁺/ 2Cl^- cotransporter 1 (NKCC1) on their apical membrane (CSF facing), deviating from the typical basolateral membrane location in chloride secretory epithelia. Given this unusual location of NKCC1 and the unknown intracellular Na⁺ and Cl^- concentrations of CPECs, the cotransporter function in these cells is not understood. Further, the direction of net ion and associated water fluxes mediated by NKCC1 under basal physiological conditions in CPECs …

A Comprehensive Dosimetric Study On Switching From A Type-B To A Type-C Dose Algorithm For Modern Lung Sbrt, Christina Zhou, Nathan Bennion, Rongtao Ma, Xiaoying Liang, Shuo Wang, Kristina Zvolanek, Megan Hyun, Xiaobo Li, Sumin Zhou, Weining Zhen, Chi Lin, Andrew Wahl, Dandan Zheng

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Background: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning.

Methods: Fifty-two lung SBRT patients were included, each …

Evolutionary History Of Chemosensory-Related Gene Families Across The Arthropoda, Seong-Il Eyun, Ho Young Soh, Marijan Posavi, James B. Munro, Daniel S.T. Hughes, Shwetha C. Murali, Jiaxin Qu, Shannon Dugan, Sandra L. Lee, Hsu Chao, Huyen Dinh, Yi Han, Harshavardhan Doddapaneni, Kim C. Worley, Donna M. Muzny, Eun-Ok Park, Joana C. Silva, Richard A. Gibbs, Stephen Richards, Carol Eunmi Lee

Nebraska Center for Biotechnology: Faculty and Staff Publications

Chemosensory-related gene (CRG) families have been studied extensively in insects, but their evolutionary history across the Arthropoda had remained relatively unexplored. Here, we address current hypotheses and prior conclusions on CRG family evolution using a more comprehensive data set. In particular, odorant receptors were hypothesized to have proliferated during terrestrial colonization by insects (hexapods), but their association with other pancrustacean clades and with independent terrestrial colonizations in other arthropod subphyla have been unclear. We also examine hypotheses on which arthropod CRG family is most ancient. Thus, we reconstructed phylogenies of CRGs, including those from new arthropod genomes and transcriptomes, and …

Investigation Of Polymeric Composites For Controlled Drug Release, Hsi-Wei Yeh

Theses and Dissertations

The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of …

Eye Movement Control: An Index For Athleticism, Brittany L. Oshea

Theses and Dissertations

Athletic potential is one of the most complex human traits. An elite athlete is produced from a complex interaction of an innumerable number of traits exhibited by the athlete. However, it’s not clear whether these traits are innate, allowing the athlete to excel, or, alternatively, are a consequence of practice. To be successful, athletes rely heavily on sensory information from the visual and vestibular systems. This study investigated the relationship eye movement control has with innate athleticism by comparing the saccadic and Vestibulo-Ocular Reflex (VOR) responses of former, no longer practicing, elite athletes against their age and gender matched counterparts …

Modified Pamam Dendrimers In Tunable Drug-Delivery Systems: A Sustained-Release Dendrimer Hydrogel For Anti-Glaucoma Drugs And Surface-Engineered Macrophages As Nanoparticle Carriers For Targeted Anti-Cancer Therapy, Christopher A. Holden

Theses and Dissertations

Two specific drug-delivery applications were sought in this work using polyamidoamine (PAMAM) dendrimers. One drug-delivery system used a novel dendrimer hydrogel (DH) for sustained delivery of anti-glaucoma drugs. In this work, PAMAM G3.0 dendrimers were covalently bonded with poly(ethylene glycol) (PEG­₁₂₀₀₀) molecules which were subsequently acrylated, resulting in photocurable DH conjugates. For pharmacological studies, DH were loaded with a solution of intraocular pressure lowering drugs, brimonidine and timolol maleate, and were characterized for in vitro release and ex vivo transport and uptake. DH formulations were shown to increase the loading of drug molecules, increase transcorneal drug delivery, and …

A Comprehensive Analysis On Eeg Signal Classification Using Advanced Computational Analysis, Kaushik Bhimraj

College of Graduate Studies: Theses & Dissertations

Electroencephalogram (EEG) has been used in a wide array of applications to study mental disorders. Due to its non-invasive and low-cost features, EEG has become a viable instrument in Brain-Computer Interfaces (BCI). These BCI systems integrate user's neural features with robotic machines to perform tasks. However, due to EEG signals being highly dynamic in nature, BCI systems are still unstable and prone to unanticipated noise interference. An important application of this technology is to help facilitate the lives of the tetraplegic through assimilating human brain impulses and converting them into mechanical motion. However, BCI systems are remarkably challenging to implement …

A Method For Measuring The Attachment Strength Of The Cestode Hymenolepis Diminuta To The Rat Intestine, Wanchuan Xie, Gábor R. Rácz, Benjamin S. Terry, Scott Lyell Gardner

Scott L. Gardner Publications

A unique adaptation of many internal parasites of mammals is their ability to stay in the intestine for extended periods of time and resist the normal peristaltic movements and forces that push and expel material. To better understand parasite adhesion behavior and replicate their attachment method in medical devices, an experiment was designed and performed using the rat tapeworm, Hymenolepis diminuta. The experiment employed a tensile test machine and a digital scale and was designed to calculate the attachment strength of the scolex to the mucosa through the change of the value of the digital scale during the tensile …

Multi-Scale Assessment Of Bone Mechanics And The Mineral Phase Of Intramuscular Bone Of Atlantic Herring Fish, Svetlana Zeveleva

Dissertations and Theses

Bone tissue is a complex composite structure made up of a soft organic phase consisting of collagen I and non-collagenous proteins, and a hard inorganic phase consisting of mineral nanoplatelets. Given it’s compositional properties, bone is a unique stiff, tough, and strong biomaterial, making it exceptionally difficult to synthesize ex vivo. While the complete hierarchical structure may change with age and population, the basic building block components of mineralized collagen fibrils, are preserved. This study uses a model of intramuscular bone of the Atlantic herring fish, which present a simple structure, and no process of remodeling.

A multi-scale approach …

Nanomedicine Drug Delivery Across Mucous Membranes, Michael G. Lancina Iii

Theses and Dissertations

NANOMEDECINE DRUG DELIVERY ACROSS MUCOUS MEMBRANES

By Michael G. Lancina III

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth Univeristy, 2017.

Major Director: Dr. Hu Yang, Associate Professor, Chemical and Life Science Engineering

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In …

Fabrication Of Flexible, Biofunctional Architectures From Silk Proteins, Ramendra K. Pal

Theses and Dissertations

Advances in the biomedical field require functional materials and processes that can lead to devices that are biocompatible, and biodegradable while maintaining high performance and mechanical conformability. In this context, a current shift in focus is towards natural polymers as not only the structural but also functional components of such devices. This poses material-specific functionalization and fabrication related questions in the design and fabrication of such systems. Silk protein biopolymers from the silkworm show tremendous promise in this regard due to intrinsic properties: mechanical performance, optical transparency, biocompatibility, biodegradability, processability, and the ability to entrap and stabilize biomolecules. The unique …

The Effect Of Vibrotactile Feedback On Remote Manual Task Performance, Matthew S. Standard

Theses and Dissertations

Vibrotactile feedback offers a unique opportunity to augment or reconstruct impaired tactile sensations, whether that be in the form of enhancing prosthetics or specialized protective clothing. Important information about temperature and object slippage serve to endanger the human operator or equipment. This thesis presents three experiments which investigate amplitude modulated vibrotactile signals as a scalar dimension of roughness, the effect those signals and their locations (finger pad, forearm, bicep) have on the performance of two tasks: the sensing of temperatures simulated by vibrotactile signals and gripping an object of simulated surface texture. The results show task performance increase when the …

Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu

Theses and Dissertations

Implanted biomaterials often induce inflammation that frequently leads to the foreign body response, fibrosis, and the failure of the implant. Thus, it is important to evaluate how cells interact with materials to promote a more regenerative response. It is critical to determine how to modulate the response of tissue resident innate immune cells, as they are among the first cells to interact with implanted materials. Among tissue resident innate immune cells are mast cells, which are inflammatory sentinels that degranulate and orchestrate the fate of other cell populations, such as monocytes/macrophages and lymphocytes. Mast cells have also been reported to …

Altering A Runner’S Foot Strike Using A Modified Elliptical Trainer, Daniel Shull

Theses and Dissertations

One possible solution to common running related injuries is to transition runners from a rearfoot strike during initial contact to a midfoot strike. Natural rearfoot strike runners were studied to see if a modified elliptical trainer could be used to alter their running pattern to that of a midfoot strike runner. Their results were compared to subjects who ran on a non-modified elliptical trainer. After training on the modified elliptical trainer, subjects demonstrated a decrease in foot angle at initial contact when attempting to run with a midfoot strike. Training did not affect all kinetic metrics or stride frequency. However, …