Biomedical Engineering and Bioengineering Commons^™

Effect Of Cold Atmospheric Plasma Treatment On The Metabolites Of Human Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Bingchuan Wang, Qingjie Cui, Zhijie Liu, Xiaohua Wang, Dingxin Liu, Hailan Chen, Michael G. Kong

Bioelectrics Publications

Background

Acute myeloid leukemia (AML) is a typically fatal malignancy and new drug and treatment need to be developed for a better survival outcome. Cold atmospheric plasma (CAP) is a novel technology, which has been widely applied in biomedicine, especially in various of cancer treatment. However, the changes in cell metabolism after CAP treatment of leukemia cells have been rarely studied.

Methods

In this study, we investigated the metabolite profiling of plasma treatment on leukemia cells based on Gas Chromatography Tandem Time-of-Flight Mass Spectrometry (GC-TOFMS). Simultaneously, we conducted a series of bioinformatics analysis of metabolites and metabolic pathways with significant …

A Survey Of Attention Deficit Hyperactivity Disorder Identification Using Psychophysiological Data, S. De Silva, S. Dayarathna, G. Ariyarathne, D. Meedeniya, Sampath Jayarathna

Computer Science Faculty Publications

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurological disorders among children, that affects different areas in the brain that allows executing certain functionalities. This may lead to a variety of impairments such as difficulties in paying attention or focusing, controlling impulsive behaviours and overreacting. The continuous symptoms may have a severe impact in the long-term. This paper explores the ADHD identification studies using eye movement data and functional Magnetic Resonance Imaging (fMRI). This study discusses different machine learning techniques, existing models and analyses the existing literature. We have identified the current challenges and possible future directions …

End-To-End Learning Via A Convolutional Neural Network For Cancer Cell Line Classification, Darlington A. Akogo, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Purpose: Computer vision for automated analysis of cells and tissues usually include extracting features from images before analyzing such features via various machine learning and machine vision algorithms. The purpose of this work is to explore and demonstrate the ability of a Convolutional Neural Network (CNN) to classify cells pictured via brightfield microscopy without the need of any feature extraction, using a minimum of images, improving work-flows that involve cancer cell identification.

Design/methodology/approach: The methodology involved a quantitative measure of the performance of a Convolutional Neural Network in distinguishing between two cancer lines. In their approach, they trained, validated and …

1995-2005: A Decade Of Innovation In Low Temperature Plasma And Its Applications, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

Scientific breakthroughs tend to come in spurts when unique societal, economical, and political circumstances conspire (knowingly or unknowingly) and create an environment ripe for creativity. The field of low temperature plasma (LTP) recently experienced such an upheaval, which this paper attempts to relate in some details. There have been “roadmap” papers published before, which look towards the future of the field, but all roads start somewhere and even “new” roads are often paved over older roads that were discovered and traveled by early pioneers. With the sharp decrease in funding for fusion research in the USA in the early 1990s …

Glioma Grading Using Structural Magnetic Resonance Imaging And Molecular Data, Syed M.S. Reza, Manar D. Samad, Zeina A. Shboul, Karra A. Jones, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

A glioma grading method using conventional structural magnetic resonance image (MRI) and molecular data from patients is proposed. The noninvasive grading of glioma tumors is obtained using multiple radiomic texture features including dynamic texture analysis, multifractal detrended fluctuation analysis, and multiresolution fractal Brownian motion in structural MRI. The proposed method is evaluated using two multicenter MRI datasets: (1) the brain tumor segmentation (BRATS-2017) challenge for high-grade versus low-grade (LG) and (2) the cancer imaging archive (TCIA) repository for glioblastoma (GBM) versus LG glioma grading. The grading performance using MRI is compared with that of digital pathology (DP) images in the …

Special Issue On Low Temperature Plasma Jets, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

[Introduction] Low temperature plasma jets are unique plasma sources capable of delivering plasma outside of the confinement of electrodes and away from gas enclosures/chambers. With these jets plasma can be easily delivered to a target located at some distance from the plasma generation region [1].

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Investigation On The Rons And Bactericidal Effects Induced By He + O2 Cold Plasma Jets: In Open Air And In An Airtight Chamber, Han Xu, Dingxin Liu, Weitao Wang, Zhijie Liu, Li Guo, Mingzhe Rong, Michael G. Kong

Bioelectrics Publications

He + O₂ plasma jets in open air and in an airtight chamber are comparatively studied, with respect to their production of gaseous/aqueous reactive species and their antibacterial effects. Under the same discharge power, the plasma jet in open air has higher densities of gaseous reactive species and a higher concentration of aqueous H₂O₂ but lower concentrations of aqueous OH and O₂^-. In addition, the increase in the O₂ ratio in He in both plasma jets causes a linear decrease in the population of gaseous reactive species, except for O(3p⁵P) …

Pneumatospinning Of Collagen Microfibers From Benign Solvents, Seth Polk, Nardos Sori, Nick Thayer, Yas Maghdouri-White, Anna A. Bulysheva, Michael P. Francis

School of Medical Diagnostics & Translational Sciences Publications

Introduction. Current collagen fiber manufacturing methods for biomedical applications, such as electrospinning and extrusion, have had limited success in clinical translation, partially due to scalability, cost, and complexity challenges. Here we explore an alternative, simplified and scalable collagen fiber formation method, termed 'pneumatospinning,' to generate submicron collagen fibers from benign solvents. Methods and results. Clinical grade type I atelocollagen from calf corium was electrospun or pneumatospun as sheets of aligned and isotropic fibrous scaffolds. Following crosslinking with genipin, the collagen scaffolds were stable in media for over a month. Pneumatospun collagen samples were characterized using Fourier-transform infrared spectroscopy, circular dichroism, …

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

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 …

Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller

Bioelectrics Publications

Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …

Antimicrobial Efficacy And Safety Of A Novel Gas Plasma-Activated Catheter Lock Solution, Sudhir Bhatt, Poonam Mehta, Chen Chen, Dayle A. Daines, Leonard A. Mermel, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 …

Epithelial Sheet Response To External Stimuli, Yashar Bashirzadeh

Mechanical & Aerospace Engineering Theses & Dissertations

Mechanical communication of adherent cells with their micro-environment is mediated by cytoskeletal and adhesion proteins. These mechanical links aid tissues in maintaining their coherence in the context of the surrounding extra cellular matrix (ECM). Epithelial tissues exert force on the ECM through integrin-based junctions and maintain their coherency through E-cadherin-based cell-cell junctions while dynamically undergoing collective migration. Such a complex network of communication involving the cell cytoskeleton and adhesion proteins modulates the tissue's response to external cues. Two distinct forms of such external stimuli are those of electrical and mechanical origin.

Epithelial tissues quickly respond to physiologically relevant electric fields …

A Stepwise Compression-Relaxation Testing Method For Tissue Characterization And Tumor Detection Via A Two-Dimensional Tactile Sensor, Yichao Yang

Mechanical & Aerospace Engineering Theses & Dissertations

This dissertation presents a stepwise compression-relaxation (SCR) testing method built upon a two-dimensional (2D) tactile sensor for mechanical characterization of soft tissues and tumor detection. The core of the 2D sensor entails one whole polydimethylsiloxane (PDMS) microstructure embedded with a 3×3 sensing-plate/transducer array. A soft sample was compressed by the 2D sensor with a step incremental depth at a ramp speed, and then relaxed for certain hold time. When a soft sample was compressed by the 2D sensor, the sensing-plates translated the sample response at different tissue sites to the sensor deflections, which were registered as resistance changes by the …

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

Study Of Abc Membrane Transporters In Single Live Cells, Preeyaporn Songkiatisak

Chemistry & Biochemistry Theses & Dissertations

The multidrug ATP-binding cassette (ABC) membrane transporters (efflux pumps) are found in both prokaryotes and eukaryotes and they can extrude diverse structurally unrelated substrates, such as antibiotics and chemotherapeutic agents out of the cells. The efflux pumps are responsible for multidrug resistance (MDR) and the failure of numerous treatments in infections and cancers. All ABC membrane transporters share a common modular topology containing two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs). The underlying molecular mechanisms regarding how the similar structural ABC membrane transporters could selectively extrude a wide variety of substrates and cause MDR, are not yet fully …

Tracing Actin Filament Bundles In Three-Dimensional Electron Tomography Density Maps Of Hair Cell Stereocilia, Salim Sazzed, Junha Song, Julio Kovacs, Willi Wriggers, Manfred Auer, Jing He

Computer Science Faculty Publications

Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, cryo-ET typically results in noisy density maps that display anisotropic XY versus Z resolution. Molecular crowding further exacerbates the challenge of automatically detecting supramolecular complexes, such as the actin bundle in hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical transduction process in inner ear sensory epithelial hair cells. Given the complexity and dense arrangement of actin …

3d Bioprinting Systems For The Study Of Mammary Development And Tumorigenesis, John Reid

Electrical & Computer Engineering Theses & Dissertations

Understanding the microenvironmental factors that control cell function, differentiation, and stem cell renewal represent the forefront of developmental and cancer biology. To accurately recreate and model these dynamic interactions in vitro requires both precision-controlled deposition of multiple cell types and well-defined three-dimensional (3D) extracellular matrix (ECM). To achieve this goal, we hypothesized that accessible bioprinting technology would eliminate the experimental inconsistency and random cell-organoid formation associated with manual cell-matrix embedding techniques commonly used for 3D, in vitro cell cultures. The first objective of this study was to adapt a commercially-available, 3D printer into a 3D bioprinter. Goal-based computer simulations were …

Understanding The Mechanical Behavior Of Costal Cartilage At Their Curved Exterior Surface Via A Tactile Sensor With A Built-In Probe For Distributed-Deflection Detection, Jiayue Shen

Mechanical & Aerospace Engineering Theses & Dissertations

This dissertation is aimed to determine the mechanical properties at the exterior surface of costal cartilages (CC) and examine how they vary with the cartilage length and the anatomical sites of CC in the ribcage via conformal indentation testing which is built upon a tactile sensor for distributed-deflection detection. The sensor entails a rectangular Polydimethylsiloxane (PDMS) microstructure sensing-plate integrated with a 5 ×1 transducer array with 0.75mm spatial resolution underneath and a built-in probe of 0.5mm×5mm×3mm above. By pressing the sensor against the exterior surface of a CC tissue with a pre-defined indentation pattern, the sensor conforms to the curved …

Non-Invasive Picosecond Pulse System For Electrostimulation, Ross Aaron Petrella

Electrical & Computer Engineering Theses & Dissertations

Picosecond pulsed electric fields have been shown to have stimulatory effects, such as calcium influx, activation of action potential, and membrane depolarization, on biological cells. Because the pulse duration is so short, it has been hypothesized that the pulses permeate a cell and can directly affect intracellular cell structures by bypassing the shielding of the membrane. This provides an opportunity for studying new biophysics. Furthermore, radiating picosecond pulses can be efficiently done by a compact antenna because the antenna size is comparable to the pulse width. However, all of the previous bioelectric studies regarding picosecond pulses have been conducted in …

Asymmetric Patterns Of Small Molecule Transport After Nanosecond And Microsecond Electropermeabilization, Esin B. Sözer, C. Florencia Pocetti, P. Thomas Vernier

Bioelectrics Publications

Imaging of fluorescent small molecule transport into electropermeabilized cells reveals polarized patterns of entry, which must reflect in some way the mechanisms of the migration of these molecules across the compromised membrane barrier. In some reports, transport occurs primarily across the areas of the membrane nearest the positive electrode (anode), but in others cathode-facing entry dominates. Here we compare YO-PRO-1, propidium, and calcein uptake into U-937 cells after nanosecond (6 ns) and microsecond (220 µs) electric pulse exposures. Each of the three dyes exhibits a different pattern. Calcein shows no preference for anode- or cathode-facing entry that is detectable with …

Alteration Of Metabolite Profiling By Cold Atmospheric Plasma Treatment In Human Myeloma Cells, Dehui Xu, Yujing Xu, Ning Ning, Qingjie Cui, Zhijie Liu, Xiaohua Wang, Dingxin Liu, Hailan Chen, Michael G. Kong

Bioelectrics Publications

BACKGROUND: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet.

METHODS: In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO 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 …

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …

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 …

A Purification And In Vitro Activity Assay For A (P)Ppgpp Synthetase From Clostridium Difficile, Astha Pokhrel, Asia Poudel, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

Kinase and pyrophosphokinase enzymes transfer the gamma phosphate or the beta-gamma pyrophosphate moiety from nucleotide triphosphate precursors to substrates to create phosphorylated products. The use of γ-³²-P labeled NTP precursors allows simultaneous monitoring of substrate utilization and product formation by radiography. Thin layer chromatography (TLC) on cellulose plates allows rapid separation and sensitive quantification of substrate and product. We present a method for utilizing the thin-layer chromatography to assay the pyrophosphokinase activity of a purified (p)ppGpp synthetase. This method has previously been used to characterize the activity of cyclic nucleotide and dinucleotide synthetases and is broadly suitable for …

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 …

Targeting Ovarian Cancer And Endothelium With An Allosteric Ptp4a3 Phosphatase Inhibitor, Kelley E. Mcqueeney, Joseph M. Salamoun, James C. Burnett, Nektarios Barabutis, Paula Pekic, Sophie L. Lewandowski, Danielle C. Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D. Catravas

Bioelectrics Publications

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, …