Bioelectrical and Neuroengineering Commons^™

Prediction Of The Outcome In Cardiac Arrest Patients Undergoing Hypothermia Using Eeg Wavelet Entropy, Hana Moshirvaziri

CGU Theses & Dissertations

Cardiac arrest (CA) is the leading cause of death in the United States. Induction of hypothermia has been found to improve the functional recovery of CA patients after resuscitation. However, there is no clear guideline for the clinicians yet to determine the prognosis of the CA when patients are treated with hypothermia. The present work aimed at the development of a prognostic marker for the CA patients undergoing hypothermia. A quantitative measure of the complexity of Electroencephalogram (EEG) signals, called wavelet sub-band entropy, was employed to predict the patients’ outcomes. We hypothesized that the EEG signals of the patients who …

Nanosecond Pulsed Electric Signals Can Affect Electrostatic Environment Of Protiens Below The Threshold Of Conformational Effects: The Case Study Of Sod1 With A Molecular Simulation Study, Elena Della Valle, Paolo Marracino, Olga Pakhomova, Micaela Liberti, Francesca Apollonio

Bioelectrics Publications

Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellular enzyme modifications triggered by the application of nanosecond pulsed electric fields. These findings were also supported by theoretical predictions from molecular dynamics simulations focussing on significant variations in protein secondary structures. In this work, a theoretical study utilizing molecular dynamics simulations is proposed to explore effects of electric fields of high intensity and very short nanosecond duration applied to the superoxide dismutase (Cu/Zn-SOD or SOD-1), an important enzyme involved in the …

Selective Distant Electrostimulation By Synchronized Bipolar Nanosecond Pulses, Elena C. Gianulis, Maura Casciola, Carol Zhou, Enbo Yang, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

A unique aspect of electrostimulation (ES) with nanosecond electric pulses (nsEP) is the inhibition of effects when the polarity is reversed. This bipolar cancellation feature makes bipolar nsEP less efficient at biostimulation than unipolar nsEP. We propose to minimize stimulation near pulse-delivering electrodes by applying bipolar nsEP, whereas the superposition of two phase-shifted bipolar nsEP from two independent sources yields a biologically-effective unipolar pulse remotely. This is accomplished by electrical compensation of all nsEP phases except the first one, resulting in the restoration of stimulation efficiency due to cancellation of bipolar cancellation (CANCAN-ES). We experimentally proved the CANCAN-ES paradigm by …

Voltage Effects On Muscarinic Acetylcholine Receptor-Mediated Contractions Of Airway Smooth Muscle, Iurii Semenov, Robert Brenner

Bioelectrics Publications

Studies have shown that the activity of muscarinic receptors and their affinity to agonists are sensitive to membrane potential. It was reported that in airway smooth muscle (ASM) depolarization evoked by high K⁺ solution increases contractility through direct effects on M3 muscarinic receptors. In this study, we assessed the physiological relevance of voltage sensitivity of muscarinic receptors on ASM contractility. Our findings reveal that depolarization by high K⁺ solution induces contraction in intact mouse trachea predominantly through activation of acetylcholine release from embedded nerves, and to a lesser extent by direct effects on M3 receptors. We therefore devised …

Neural Coding Of An Auditory Pitch Illusion, Maria Alejandra Barrera, Mark Sayles, Ravinderjit Singh

The Summer Undergraduate Research Fellowship (SURF) Symposium

Pitch is an important perceptual dimension in audition, supporting auditory object segregation, melody recognition and lexical distinction. Huggins’ pitch, for example, is a phenomenon evoked by two sources of broadband noise presented binaurally with an inter-aural phase shift over a narrow frequency band. Huggins’ pitch and other dichotic pitches have been studied extensively using perceptual experiments. Several models have been proposed to explain and predict the perception of pitch; however, no studies have tried to record in vivo neuron responses to Huggins’ pitch (HP) nor have tried to explain how the HP is coded by neurons. The existence of pitches …

Intercellular Sodium Nanodomain Signaling Regulates Repolarization In Cardiac Tissue, Madison Nowak, Seth Weinberg Ph.D.

Biology and Medicine Through Mathematics Conference

No abstract provided.

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 …

Asd Biomarker Detection On Fmri Images: Feature Learning With Data Corruptions By Analyzing Deep Neural Network Classifier Outcomes, Xiaoxiao Li 6984086

Yale Day of Data

Autism spectrum disorder (ASD) is a complex neurological and developmental disorder. It emerges early in life and is generally associated with lifelong disability. Finding the biomarkers associated with ASD is extremely helpful to understand the underlying roots of the disorder and find more targeted treatment. Previous studies suggested brain activations are abnormal in ASDs, hence functional magnetic resonance imaging (fMRI) has been used to identify ASD. In this work we addressed the problem of interpreting reliable biomarkers in classifying ASD vs. control; therefore, we proposed a 2-step pipeline: 1) classifying ASD and control fMRI images by deep neural network, and …

Nano-Pulse Stimulation Ablates Orthotopic Rat Hepatocellular Carcinoma And Induces Innate And Adaptive Memory Immune Mechanisms That Prevent Recurrence, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

Bioelectrics Publications

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME …

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding …

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Nanopulse Stimulation (Nps) Induces Tumor Ablation And Immunity In Orthotopic 4t1 Mouse Breast Cancer: A Review, Stephen J. Beebe, Brittany P. Lassiter, Siqi Guo

Bioelectrics Publications

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases …

Delayed Hypersensitivity To Nanosecond Pulsed Electric Field In Electroporated Cells, Sarah D. Jensen, Vera A. Khorokhorina, Claudia Muratori, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

We demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3–100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. …

Damage-Free Peripheral Nerve Stimulation By 12-Ns Pulsed Electric Field, Maura Casciola, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1-11 kV (3.3-8.8 kV/cm) evoked APs similarly to conventional stimuli (100-250 mus, 1-5 V, 103-515 V/m), …

Controllable Moderate Heating Enhances The Therapeutic Efficacy Of Irreversible Electroporation For Pancreatic Cancer, Chelsea M. Edelblute, James Hornef, Niculina I. Burcus, Thomas Norman, Stephen J. Beebe, Karl Schoenbach, Richard Heller, Chunqi Jiang, Sigi Guo

Bioelectrics Publications

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43°C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the …

Co-Modulation Masking Release Begins In The Auditory Periphery, Kareem R. Hussein, Agudemu Borjigan, Mark Sayles

The Summer Undergraduate Research Fellowship (SURF) Symposium

Understanding speech in noisy environments can be difficult, especially for people with hearing loss. The background noise can cover up the sounds of interest. Normally, the auditory system works to alleviate this problem by tagging and then cancelling the noise. Our experiments are aimed at understanding the mechanism of this noise cancellation process. We hypothesize that non-linear signal processing in the mammalian cochlea (the most peripheral part of the auditory system) is the basis of noise cancellation. To test this hypothesis, we measured the responses of auditory-nerve fibers (ANFs) to sounds embedded in background noise with different statistical properties. ANFs …

Anaplasma Phagocytophilum Infection Modulates Expression Of Megakaryocyte Cell Cycle Genes Through Phosphatidylinositol-3-Kinase Signaling, Supreet Khanal, Hameeda Sultana, John D. Catravas, Jason A. Carlyon, Girish Neelakanta

Biological Sciences Faculty Publications

Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis infects neutrophils and other cells from hematopoietic origin. Using human megakaryocytic cell line, MEG-01, we show that expression of cell cycle genes in these cells are altered upon A. phagocytophilum infection. Expression of several cell cycle genes in MEG-01 cells was significantly up regulated at early and then down regulated at later stages of A. phagocytophilum infection. Lactate dehydrogenase (LDH) assays revealed reduced cellular cytotoxicity in MEG-01 cells upon A. phagocytophilum infection. The levels of both PI3KCA (p110 alpha, catalytic subunit) and PI3KR1 (p85, regulatory subunit) of Class …

Role Of Trpv4 In Astrocyte Extracellular Matrix Production, Abby Terlouw

Biomedical Engineering Undergraduate Honors Theses

Traumatic Brain Injury (TBI) is an alteration of brain pathology following damage of the central nervous system (CNS) by an external force. In the CNS, glial scar formation often occurs following TBI, and astrocytes are widely believed to contribute to this scar formation. While the role of astrocytes in extracellular matrix (ECM) production is known, the exact mechanism(s) for this event remain unclear. One possible method is the activation of transient receptor potential vanilloid 4 (TRPV4). TRPV4 is a channel protein found in the astrocyte membrane which has been shown to generate intracellular calcium ions following mechanical stimulation. Previous research …

Electrotransfer Of Plasmid Dna Radiosensitizes B16f10 Tumors Through Activation Of Immune Response, Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa

Bioelectrics Publications

Background. Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors.

Materials and methods. The murine melanoma Bl6F10 tumors, growing on the back of C57BI/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, …

Transient Alt Activation Protects Human Primary Cells From Chromosome Instability Induced By Low Chronic Oxidative Stress, Elisa Coluzzi, Rossella Buonsante, Stefano Leone, Anthony J. Asmar, Kelley L. Miller, Daniela Cimini, Antonella Sgura

Bioelectrics Publications

Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres …

Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker

Graduate Theses and Dissertations

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of …

Mechanical Reliability Of Implantable Polyimide-Based Magnetic Microactuators For Biofouling Removal, Christian G. Figueroa-Espada, Qi Yang, Hyowon Lee

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hydrocephalus is a neurological disorder that typically requires a long-term implantation of a shunt system to manage its symptoms. These shunt systems are notorious for their extremely high failure rate. More than 40% of all implanted shunt systems fail within the first year of implantation. On average, 85% of all hydrocephalus patients with shunt systems undergo at least two shunt-revision surgeries within 10 years of implantation. A large portion of this high failure rate can be attributed to biofouling-related obstructions and infections. Previously, we developed flexible polyimide-based magnetic microactuators to remove obstructions formed on hydrocephalus shunts. To test the long-term …

Cytosolic Dna Sensor Upregulation Accompanies Dna Electrotransfer In B16.F10 Melanoma Cells, Katarina Znidar, Masa Bosnjak, Maja Cemazar, Loree C. Heller

Bioelectrics Publications

In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFN β mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16. F10 …

Noninvasive Measurement Of Electrical Events Associated With A Single Chlorovirus Infection Of A Microalgal Cell, Seung-Woo Lee, Eun-Hee Lee, Gerhard Thiel, James L. Van Etten, Ravi Saraf

Department of Chemical and Biomolecular Engineering: Faculty Publications

Chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains a viral-encoded K⁺ channel imbedded in its internal membrane, which triggers host plasma membrane depolarization during virus infection. This early stage of infection was monitored at high resolution by recording the cell membrane depolarization of a single Chlorella cell during infection by a single PBCV-1 particle. The measurement was achieved by depositing the cells onto a network of one-dimensional necklaces of Au nanoparticles, which spanned two electrodes 70 μm apart. The nanoparticle necklace array has been shown to behave as a single-electron device at room temperature. The resulting electrochemical field-effect transistor …

Experimental-Computational Analysis Of Vigilance Dynamics For Applications In Sleep And Epilepsy, Farid Yaghouby

Theses and Dissertations--Biomedical Engineering

Epilepsy is a neurological disorder characterized by recurrent seizures. Sleep problems can cooccur with epilepsy, and adversely affect seizure diagnosis and treatment. In fact, the relationship between sleep and seizures in individuals with epilepsy is a complex one. Seizures disturb sleep and sleep deprivation aggravates seizures. Antiepileptic drugs may also impair sleep quality at the cost of controlling seizures. In general, particular vigilance states may inhibit or facilitate seizure generation, and changes in vigilance state can affect the predictability of seizures. A clear understanding of sleep-seizure interactions will therefore benefit epilepsy care providers and improve quality of life in patients. …

In Situ Oh Generation From O2- And H2o2 Plays A Critical Role In Plasma Induced Cell Death, Dehui Xu, Dingxing Liu, Biqing Wang, Chen Chen, Zeyu Chen, Dong Li, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

Reactive oxygen and nitrogen species produced by cold atmospheric plasma (CAP) are considered to be the most important species for biomedical applications, including cancer treatment. However, it is not known which species exert the greatest biological effects, and the nature of their interactions with tumor cells remains ill-defined. These questions were addressed in the present study by exposing human mesenchymal stromal and LP-1 cells to reactive oxygen and nitrogen species produced by CAP and evaluating cell viability. Superoxide anion (O₂-) and hydrogen peroxide (H₂O₂) were the two major species present in plasma, but their …

Tht And Capillary Electrophoresis To Monitor The Effects Of Solutions Conditions On Amylin Aggregation, Michael May

Graduate Theses and Dissertations

Amylin (hIAPP) aggregates have been found in 90% of patients with type II diabetes at autopsy, and are suspected to play a role in the death of islet &beta-cells¹. However, this aggregation process is not well understood. Here, we explore methods that utilize capillary electrophoresis (CE) as a means to better understand amylin's aggregation process.

We examined the effects of solutions conditions: agitation, pH, salt, and temperature on amylin aggregation using Thioflavin T, dot blots, and capillary electrophoresis. Thiofalvin T was used to predict the lag time to &beta-sheet formation. Our results indicated all variables with the exception …

Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok

Bioelectrics Publications

BACKGROUND: Chondrocytes respond to biomechanical and bioelectrochemical stimuli by secreting appropriate extracellular matrix proteins that enable the tissue to withstand the large forces it experiences. Although biomechanical aspects of cartilage are well described, little is known of the bioelectrochemical responses. The focus of this study is to identify bioelectrical characteristics of human costal cartilage cells using dielectric spectroscopy.

METHODS: Dielectric spectroscopy allows non-invasive probing of biological cells. An in house computer program is developed to extract dielectric properties of human costal cartilage cells from raw cell suspension impedance data measured by a microfluidic device. The dielectric properties of chondrocytes are …

Electrotransfer Of Single-Stranded Or Double-Stranded Dna Induces Complete Regression Of Palpable B16.F10 Mouse Melanomas, Loree Heller, Vesba Todorovic, Maja Cemazar

Bioelectrics Publications

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both …

The Development Of A Traumatic Brain Injury Bioreactor, Zachery Heller

Graduate Theses and Dissertations

Approximately 1.7 million Americans experience a traumatic brain injury (TBI) each year. Concussive injuries are a subset of TBI in which blows to the head cause the brain to collide against the interior of the skull. Damage to the neurons, supporting cells, and surrounding extra cellular matrix resulting from these collisions can lead to permanent physical, cognitive, and psychological impairment. We believe the prevalence and clinical significance of concussive injures warrants research investment. To study brain injury following TBI, in vivo models have been the gold standard for TBI experiments. Although a valuable research alternative, animals are expensive, raise ethical …