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Applications For Pulse Power Using Nanosecond Pulsed Electric Fields (Nspefs) In Cell Biology And Cancer Treatment, Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

Electroporation-Mediated Gene Transfer Directly To The Swine Heart, Barbara Hargrave, Harre Downey, Cathryn Lundberg, Annelise Israel, Yeong-Jer Chen, Richard Heller

Bioelectrics Publications

In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using three different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the electrocardiogram were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on …

Topical Gene Electrotransfer To The Epidermis Of Hairless Guinea Pig By Non-Invasive Multielectrode Array, Sigi Guo, Annelise L. Israel, Gaurav Basu, Amy Donate, Richard Heller

Bioelectrics Publications

Topical gene delivery to the epidermis has the potential to be an effective therapy for skin disorders, cutaneous cancers, vaccinations and systemic metabolic diseases. Previously, we reported on a non-invasive multielectrode array (MEA) that efficiently delivered plasmid DNA and enhanced expression to the skin of several animal models by in vivo gene electrotransfer. Here, we characterized plasmid DNA delivery with the MEA in a hairless guinea pig model, which has a similar histology and structure to human skin. Significant elevation of gene expression up to 4 logs was achieved with intradermal DNA administration followed by topical non-invasive skin gene electrotransfer. …

Two Modes Of Cell Death Caused By Exposure To Nanosecond Pulsed Electric Field, Olga N. Pakhomova, Betsy W. Gregory, Iurii Semenov, Andrei G. Pakhomov

Bioelectrics Publications

High-amplitude electric pulses of nanosecond duration, also known as nanosecond pulsed electric field (nsPEF), are a novel modality with promising applications for cell stimulation and tissue ablation. However, key mechanisms responsible for the cytotoxicity of nsPEF have not been established. We show that the principal cause of cell death induced by 60- or 300-ns pulses in U937 cells is the loss of the plasma membrane integrity (‘‘nanoelectroporation’’), leading to water uptake, cell swelling, and eventual membrane rupture. Most of this early necrotic death occurs within 1–2 hr after nsPEF exposure. The uptake of water is driven by the presence of …

Cell Responses Without Receptors And Ligands, Using Nanosecond Pulsed Electric Fields (Nspefs), Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

Bioelectrics In Basic Science And Medicine: Impact Of Electric Fields On Cellular Structures And Functions, Stephen J. Beebe

Bioelectrics Publications

Bioelectrics is a new interdisciplinary field that investigates electric field effects on cell membranes and other cellular components. It incorporates four main technologies, including electroporation, nanosecond pulsed electric fields, picosecond pulsed electric fields and cold plasmas. The parent technology in Bioelectrics is electroporation, which uses milli- and/or micro-second electric pulses to permeabilize cells and tissues, for delivery of membrane impermeable molecules. It is now being used for electro-gene delivery, with vascular endothelial growth factor, for revascularization in wound healing and cardiovascular and peripheral vascular disease. Plasmids expressing IL-12 are being delivered for immune system activation in melanoma treatment, now in …

Facilitation Of Electroporative Drug Uptake And Cell Killing By Electrosensitization, Olga N. Pakhomova, Betsy W. Gregory, Andrei G. Pakhomov

Bioelectrics Publications

Cell permeabilization by electric pulses (EP), or electroporation, is widely used for intracellular delivery of drugs and plasmids, as well as for tumour and tissue ablation. We found that cells pre-treated with 100-mus EP develop delayed hypersensitivity to subsequent EP applications. Sensitizing B16 and CHO cells by splitting a single train of eight 100-mus EP into two trains of four EP each (with 5-min. interval) decreased the LD(50) 1.5-2 times. Sensitization profoundly enhanced the electroporation-assisted uptake of bleomycin, a cell-impermeable cytotoxic agent accepted for killing tumours by electrochemotherapy. EP exposures that were not lethal per se caused cell death in …

Late Developing Mammary Tumors And Hyperplasia Induced By A Low-Oncogenic Variant Of Mouse Mammary Tumor Virus (Mmtv) Express Genes Identical To Those Induced By Canonical Mmtv, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of …

Embryonic Stem Cells Are Redirected To Non-Tumorigenic Epithelial Cell Fate By Interaction With The Mammary Microenvironment, Corinne A. Boulanger, Robert D. Bruno, David L. Mack, Monica Gonzales, Nadia P. Castro, David S. Salomon, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Publications

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We …

Conformational Sampling In Template Free Protein Loop Structure Modeling: An Overview, Yaohang Li

Computer Science Faculty Publications

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a "mini protein folding problem" under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the …

Review Of Us And Eu Initiatives Toward Development, Demonstration, And Commercialization Of Lignocellulosic Biofuels, Venkatesh Balan, David Chiaramonti, Sandeep Kumar

Civil & Environmental Engineering Faculty Publications

Advanced biofuels produced from lignocellulosic biomass offer an exciting opportunity to produce renewable liquid transportation fuels, biochemicals, and electricity from locally available agriculture and forest residues. The growing interest in biofuels from lignocellulosic feedstock in the United States (US) and the European Union (EU) can provide a path forward toward replacing petroleum-based fuels with sustainable biofuels which have the potential to lower greenhouse gas (GHG) emissions. The selection of biomass conversion technologies along with feedstock development plays a crucial role in the commercialization of next-generation biofuels. There has been synergy and, even with similar basic process routes, diversity in the …

Cumulative Response Of Ecosystem Carbon And Nitrogen Stocks To Chronic Co2 Exposure In A Subtropical Oak Woodland, Bruce A. Hungate, Paul Dijkstra, Zhuoting Wu, Benjamin D. Duval, Frank P. Day, Alisha L.P. Brown

Biological Sciences Faculty Publications

·Rising atmospheric carbon dioxide (CO₂) could alter the carbon (C) and nitrogen (N) content of ecosystems, yet the magnitude of these effects are not well known. We examined C and N budgets of a subtropical woodland after 11 yr of exposure to elevated CO₂.

·We used open-top chambers to manipulate CO₂ during regrowth after fire, and measured C, N and tracer ¹⁵N in ecosystem components throughout the experiment.

·Elevated CO₂ increased plant C and tended to increase plant N but did not significantly increase whole-system C or N. Elevated CO₂ increased soil …

Habitat Availability And Heterogeneity And The Indo-Pacific Warm Pool As Predictors Of Marine Species Richness In The Tropical Indo-Pacific, Jonnell C. Sanciangco, Kent E. Carpenter, Peter J. Etnoyer, Fabio Moretzsohn

Biological Sciences Faculty Publications

Range overlap patterns were observed in a dataset of 10,446 expert-derived marine species distribution maps, including 8,295 coastal fishes, 1,212 invertebrates (crustaceans and molluscs), 820 reef-building corals, 50 seagrasses, and 69 mangroves. Distributions of tropical Indo-Pacific shore fishes revealed a concentration of species richness in the northern apex and central region of the Coral Triangle epicenter of marine biodiversity. This pattern was supported by distributions of invertebrates and habitat-forming primary producers. Habitat availability, heterogeneity, and sea surface temperatures were highly correlated with species richness across spatial grains ranging from 23,000 to 5,100,000 km(2) with and without correction for autocorrelation. The …

Cooperative Breeding And Long-Distance Dispersal: A Test Using Vagrant Records, Caroline L. Rusk, Eric L. Walters, Walter D. Koenig

Biological Sciences Faculty Publications

Cooperative breeding is generally associated with increased philopatry and sedentariness, presumably because short-distance dispersal facilitates the maintenance of kin groups. There are, however, few data on long-distance dispersal in cooperative breeders-the variable likely to be important for genetic diversification and speciation. We tested the hypothesis that cooperative breeders are less likely to engage in long-distance dispersal events by comparing records of vagrants outside their normal geographic range for matched pairs (cooperatively vs. non-cooperatively breeding) of North American species of birds. Results failed to support the hypothesis of reduced long-distance dispersal among cooperative breeders. Thus, our results counter the conclusion that …

Age-Associated Metabolic And Morphologic Changes In Mitochondria Of Individual Mouse And Hamster Oocytes, Fatma Simsek-Duran, Fang Li, Wentia Ford, R. James Swanson, Howard W. Jones Jr., Frank J. Castora

Biological Sciences Faculty Publications

Background: In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function. In this study, we have examined mitochondrial biogenesis in both hamster (Mesocricetus auratus) and mouse (Mus musculus) ova as models for understanding the effects of aging on mitochondrial structure and energy production within the mammalian oocyte.

Methodology/Principal Findings: Individual metaphase …

Does Pitcher Plant Morphology Affect Spider Residency?, Marc A. Milne, Deborah A. Waller

Biological Sciences Faculty Publications

Spiders are often found as residents in association with Sarracenia purpurea ( Purple Pitcher Plant). Many spiders choose web locations based on environmental cues such as vegetation structure and composition, prey density, temperature, and humidity. To determine if spiders use cues from the Purple Pitcher Plant to build their webs, we conducted a field study using variants of the plant that separated various morphological features: nectar, pigment, and the presence of prey. There was no difference in spider residency across all treatments and no difference in male/female or mature/immature residency. Linyphiids were the most common residents, possibly due to pitcher …

Chemical Defense Of An Asian Snake Reflects Local Availability Of Toxic Prey And Hatchling Diet, D. A. Hutchinson, A. H. Savitzky, G. M. Burghardt, C. Nguyen, J. Meinwald, F. C. Schroeder, A. Mori

Biological Sciences Faculty Publications

Species that sequester toxins from prey for their own defense against predators may exhibit population-level variation in their chemical arsenal that reflects the availability of chemically defended prey in their habitat. Rhabdophis tigrinus is an Asian snake that possesses defensive glands in the skin of its neck (nuchal glands'), which typically contain toxic bufadienolide steroids that the snakes sequester from consumed toads. In this study, we compared the chemistry of the nuchal gland fluid of R.tigrinus from toad-rich and toad-free islands in Japan and determined the effect of diet on the nuchal gland constituents. Our findings demonstrate that captive-hatched juveniles …

Genetic Population Structure Of Us Atlantic Coastal Striped Bass (Morone Saxatilis), David T. Gauthier, Corinne A. Audemard, Jeanette E. L. Carlsson, Tanya L. Darden, Michael R. Denson, Kimberly S. Reece, Jens Carlsson

Biological Sciences Faculty Publications

Genetic population structure of anadromous striped bass along the US Atlantic coast was analyzed using 14 neutral nuclear DNA microsatellites. Young-of-the-year and adult striped bass (n = 1114) were sampled from Hudson River, Delaware River, Chesapeake Bay, North Carolina, and South Carolina. Analyses indicated clear population structure with significant genetic differentiation between all regions. Global multilocus F-ST was estimated at 0.028 (P < 0.001). Population structure followed an isolation-by-distance model and temporal sampling indicated a stable population structure more than 2 years at all locations. Significant structure was absent within Hudson River, whereas weak but significant genetic differences were observed between northern and southern samples in Chesapeake Bay. The largest and smallest effective striped bass population sizes were found in Chesapeake Bay and South Carolina, respectively. Coalescence analysis indicated that the highest historical gene flow has been between Chesapeake Bay and Hudson River populations, and that exchange has not been unidirectional. Bayesian analysis of contemporary migration indicated that Chesapeake Bay serves as a major source of migrants for Atlantic coastal regions from Albemarle Sound northward. In addition to examining population genetic structure, the data acquired during this project were capable of serving as a baseline for assigning fish with unknown origin to source region.

Experiences And Perceptions Of Mental Health Professionals Considered Effective In The Diagnosis And Treatment Of Adults With Attention Deficit Hyperactivity Disorder, Bonita H. Erb

Counseling & Human Services Theses & Dissertations

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder that has been documented in medical and mental health literature for over 100 years (Still, 1902). ADHD is a neurobiological based disorder characterized by three major symptoms identified at clinical levels and validated by diagnostic criteria established for the diagnosis of children before the age of seven (Diagnostic and Statistical Manual of Mental Disorders, 4 th edition-Text Revision; DSM-IV; American Psychiatric Association, 2000). The three diagnostic criteria are inattention, impulsivity, and hyperactivity that have been observed at clinical levels.

Because many signs of the disorder were believed to discontinue …

An Examination Of The Predictive Relationship Between Mode Of Instruction And Student Success In Introductory Biology, Lynette Kathleen Hauser

Educational Leadership & Workforce Development Theses & Dissertations

Community colleges continue to increase online course offerings as these institutions strive to offer open access, cost effective education to a growing student population. With an increased student demand for online learning, community colleges should explore the possibility of offering all courses in the online environment, including science courses. The purpose of this quantitative research was to investigate the success of non-science major students in biology 102 on campus comparing students who completed biology 101 online to students who completed biology 101 on campus within Virginia community colleges. This was the first multi institutional, multi semester study of community college …

System Governance Analysis Of Complex Systems, Behnido Y. Calida

Engineering Management & Systems Engineering Theses & Dissertations

The purpose of this research was to develop and deploy a systems-based framework for analysis of complex governance systems using a multimethodology research design. Two research gaps motivated this research: (1) lack of an integrated conceptualization of a system governance construct, (2) an absence of studies that consider both the governed and governing systems as well as the emergent interactions that arise from within complex governance systems.

The research focused on three primary questions: (1) What are the distinctive characteristics of governance?; (2) What system-based framework can be developed for analysis of governance in complex systems?, and (3) What results …

New Tools For Real-Time Study Of Embryonic Development, Lauren M. Browning

Theses and Dissertations in Biomedical Sciences

Embryonic development represents one of the most complex and dynamic cellular processes in biology, and plays vital roles in understanding of functions of embryonic stem cells (ESCs) and design of ESC-based therapy. Conventional assays and fluorescence-based imaging methods have been widely used for the study of embryonic development. These conventional methods cannot effectively provide spatial and temporal resolutions with sufficient sensitivity and selectivity that are required to depict embryonic development in vivo in real-time at single-cell and single-molecule resolutions. In this dissertation, we have developed a wide range of innovative tools for real-time study of embryonic development. These new tools …

A Polymer-Based Microfluidic Device With Electrolyte-Enabled Distributed Transducers (Eedt) For Distributed Load Detection, Peng Cheng

Mechanical & Aerospace Engineering Theses & Dissertations

The capability of detecting distributed static and dynamic loads is indispensable in a wide variety of applications, such as examining anatomical structures of biological tissues in tissue health analysis and minimally invasive surgery (MIS) and determining the texture of an object in robotics. This dissertation presents a comprehensive study of a polymer-based microfluidic device with electrolyte-enabled distributed transducers and demonstrates a new concept on using a single microfluidic device for distributed-load detection, which takes advantage of the low-cost microfluidic fabrication technology and the low modulus and biocompatibility of polymer. The core of the device is a single deformable polymer microstructure …

Attachment Ability And Melanoma Inhibitory Activity Mrna Expression Level Changes In Murine B16-F10 Melanoma Cells Post Nanosecond Electric Pulses, Hongxia Jia

Theses and Dissertations in Biomedical Sciences

The effects of high-voltage nanosecond electric pulses (nsEPs) on metastatic melanoma are still unclear. Hence, we applied one, two, three, and four 300 ns 40 kV/cm pulses to murine B16-F10 melanoma cells. Cell attachment ability was determined by comparing the number of floating cells and the percentage of attached cells. Melanoma inhibitory activity (MIA) is a secretory protein that is highly correlated with the malignancy and metastasis of malignant melanomas. We used MIA as our target to evaluate the effect of nsEPs on metastasis. Pulsed (experimental) and unpulsed (control) cells were incubated at 37°C under a 5% CO₂ atmosphere. …

Analysis And Simulation Of Kinetic Model For Active Suspensions, Panon Phuworawong

Mathematics & Statistics Theses & Dissertations

In this research, we study the recently proposed kinetic model for active suspensions, where the active particles are assumed to be rigid rod and are driven in the suspension either by their own biological/chemical forces or external electric/magnetic fields. We first study the stability of the isotropic suspension in quiescent flow. Then we investigate the weak shear perturbation of the isotropic state and study some rheological properties of the suspension by explicit analytic formulas derived directly from the model. For imposed shear, we give some bifurcation diagrams of the stable states in some parametric spaces through numerical simulations. Some rheological …

Effect Of Sensory Modality On Performance Workload And Frontal Lobe Oxygenation In A Standard Vigilance Task, Veronica Emily Scerra

Psychology Theses & Dissertations

Performance, subjective workload, and frontal lobe oxygenation measures were collected from observers monitoring visual, auditory, or vibrotactile signals. Critical signals for detection in each sensory modality were stimuli of reduced duration, which were equated for perceptual salience and discriminability. Perceptual sensitivity to targets and the percentage of correct detections declined significantly over time for all sensory modalities, with significantly greater performance decrements for the visual modality than for the auditory and tactile modalities. Frontal lobe oxygenation, as recorded by functional near infrared spectroscopy 0NIR), increased over time in task conditions as compared to a control (no work imperative) condition, but …

Observations And Modeling Forcing Mechanisms For The Coastal Dynamics Of The Upper Gulf Of Thailand, Suriyan Saramul

OES Theses and Dissertations

A numerical model based on the Princeton Ocean Model (130M) with ∼1 km horizontal grid and 21 vertical layers has been used to study the influence of wind stresses, river discharges, surface heat fluxes and tides on the three-dimensional circulation of the upper Gulf of Thailand (UGOT). Analysis of observations, including sea level data, provided additional information to support the model simulations. The UGOT is a shallow coastal system, ∼1°×1° in size with the average depth of only 15 m. Sensitivity studies evaluate how the dynamics is affected by surface wind stresses, river discharges, and surface heat fluxes. The impact …

Structural And Functional Study Of Multidrug Membrane Transporters, Feng Ding

Theses and Dissertations in Biomedical Sciences

Multidrug membrane transporters (efflux pumps) in both prokaryotes and eukaryotes are responsible for ineffective treatment of a wide variety of diseases, including infections and cancer, underscoring the importance of better understanding of their structures and functions for design of effective therapies. Despite extensive studies over decades, their underlying molecular mechanisms remain largely unknown. In this dissertation, we focus on the study of structures and functions of multidrug membrane transporters, including ATP-binding cassette transporter (BmrA) and Resistance-Nodulation-Cell Division transporter (MexA,B-OprM) in gram-positive and gram-negative bacteria ( Bacillus subtilis and Pseudomonas aeruginosa), respectively. We fused EGFP with N-terminus and C-terminus of …

In Search For Instructional Techniques To Maximize The Use Of Germane Cognitive Resources: A Case Of Teaching Complex Tasks In Physics, Yekaterina Sliva

STEMPS Theses & Dissertations

The purpose of this study was to introduce an instructional technique for teaching complex tasks in physics, test its effectiveness and efficiency, and understand cognitive processes taking place in learners' minds while they are exposed to this technique. The study was based primarily on cognitive load theory (CLT). CLT determines the amount of total cognitive load imposed on a learner by a learning task as combined intrinsic (invested in comprehending task complexity) and extraneous (wasteful) cognitive load. Working memory resources associated with intrinsic cognitive load are defined as germane resources caused by element interactivity that lead to learning, in contrast …

The 6th Computational Structural Bioinformatics Workshop Introduction, Jing He, Amarda Shehu, Nurit Haspel, Brian Chen

Computer Science Faculty Publications

No abstract provided.