Engineering Commons^™

Activation Of The Phospholipid Scramblase Tmem16f By Nanosecond Pulsed Electric Field (Nspef) Facilitates Its Diverse Cytophysiological Effects, Claudia Muratori, Andrei G. Pakhomov, Elena Gianulis, Jade Meads, Maura Casciola, Peter A. Mollica, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields (nsPEF) are emerging as a novel modality for cell stimulation and tissue ablation. However, the downstream protein effectors responsible for nsPEF bioeffects remain to be established. Here we demonstrate that nsPEF activate TMEM16F (or Anoctamin 6), a protein functioning as a Ca²⁺-dependent phospholipid scramblase and Ca²⁺-activated chloride channel. Using confocal microscopy and patch clamp recordings, we investigated the relevance of TMEM16F activation for several bioeffects triggered by nsPEF, including phosphatidylserine (PS) externalization, nanopore-conducted currents, membrane blebbing, and cell death. In HEK 293 cells treated with a single 300-ns pulse of 25.5 kV/cm, …

A Picture Is Worth A Thousand Roads, Keith Pierce

News Items

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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. …

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 …

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), …

A Systems-Based Framework For Design And Analysis Of An R And D Structure, Polinpapilinho F. Katina, Charles B. Keating, Luna M. Magpili

Engineering Management & Systems Engineering Faculty Publications

A critical challenge for managerial effectiveness and competitive advantage in research and development (R and D) organizations is developing an appropriate structural configuration. However, in finding an appropriate structural configuration, R and D managers are faced with unprecedented levels of uncertainty, ambiguity, and accelerating complexity, coupled with demands for increased productivity. This paper develops a systems-based framework to support rigorous design, analysis, and transformation of the structure for R and D organizations. The framework development includes: (1) a review of the literature for the nature and role of the structure in R and D management; (2) setting of the R …

Defects In Skeletal Muscle Subsarcolmmal Mitochondria In A Non-Obese Model Of Type 2 Diabetes Mellitus, Nicola Lai, China Kummitha, Charles Hoppel

Electrical & Computer Engineering Faculty Publications

Skeletal muscle resistance to insulin is related to accumulation of lipid-derived products, but it is not clear whether this accumulation is caused by skeletal muscle mitochondrial dysfunction. Diabetes and obesity are reported to have a selective effect on the function of subsarcolemmal and interfibrillar mitochondria in insulin-resistant skeletal muscle. The current study investigated the role of the subpopulations of mitochondria in the pathogenesis of insulin resistance in the absence of obesity. A non-obese spontaneous rat model of type 2 diabetes mellitus, (Goto-Kakizaki), was used to evaluate function and biochemical properties in both populations of skeletal muscle mitochondria. In subsarcolemmal mitochondria, …

Nanostructure Evolution Of Magnetron Sputtered Hydrogenated Silicon Thin Films, Dipendra Adhikari, Maxwell M. Junda, Sylvain X. Marsillac, Robert W. Collins, Nikolas J. Podraza

Electrical & Computer Engineering Faculty Publications

Hydrogenated silicon (Si:H) thin films have been prepared by radio frequency (RF) magnetron sputtering. The effect of hydrogen gas concentration during sputtering on the resultant film structural and optical properties has been investigated by real time spectroscopic ellipsometry (RTSE) and grazing incidence x-ray diffraction (GIXRD). The analysis of in-situ RTSE data collected during sputter deposition tracks the evolution of surface roughness and film bulk layer thickness with time. Growth evolution diagrams depicting amorphous, nanocrystalline and mixed-phase regions for low and high deposition rate Si:H are constructed and the effects of process parameter (hydrogen gas concentration, total pressure and RF power) …

Optimal Control-Based Inverse Determination Of Electrode Distribution For Electroosmotic Micromixer, Yuan Li, Yongbo Deng, Zhenyu Liu, Teng Zhou, Yihui Wu, Shizhi Qian

Mechanical & Aerospace Engineering Faculty Publications

This paper presents an optimal control-based inverse method used to determine the distribution of the electrodes for the electroosmotic micromixers with external driven flow from the inlet. Based on the optimal control method, one Dirichlet boundary control problem is constructed to inversely find the optimal distribution of the electrodes on the sidewalls of electroosmotic micromixers and achieve the acceptable mixing performance. After solving the boundary control problem, results are also provided to demonstrate the effectiveness of the proposed method; the step-shaped distribution of the external electric potential imposed on the sidewalls is obtained, and the electrodes with an interlaced arrangement …

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 …

The Effect Of Magnification Loupes On Dental Hygienists' Posture While Exploring, Emily Ludwig, Gayle B. Mccombs, Susan L. Tolle, Daniel M. Russell

Dental Hygiene Faculty Publications

Purpose: The purpose of this study was to determine the effects of dental magnification loupes on posture during instrumentation.

Methods: A convenience sample of 27 right-handed dental hygienists, with no prior history of injuries or disabilities of the head, neck, or trunk region, enrolled in the study. Baseline posture calibration was taken and tri-axial accelerometers were placed on four locations of the head and trunk (occipital region of head; cervical vertebrae C5; thoracic vertebrae T5; lumbar vertebrae L1) to measure acceleration and the orientation of the body to gravity. Participants were randomly assigned to wear self-supplied magnification loupes during either …

Nanosecond Electric Pulses Differentially Affect Inward And Outward Currents In Patch Clamped Adrenal Chromaffin Cells, Lisha Yang, Gale L. Craviso, P. Thomas Vernier, Indira Chatterjee, Normand Leblanc

Bioelectrics Publications

This study examined the effect of 5 ns electric pulses on macroscopic ionic currents in whole-cell voltage-clamped adrenal chromaffin cells. Current-voltage (I-V) relationships first established that the early peak inward current was primarily composed of a fast voltage-dependent Na⁺ current (I_Na), whereas the late outward current was composed of at least three ionic currents: a voltage-gated Ca²⁺ current (I_Ca), a Ca²⁺-activated K⁺ current (I_K(Ca)), and a sustained voltage-dependent delayed rectifier K⁺ current (I_KV). A constant-voltage step protocol was next used to monitor peak inward and late …

Perspective: The Physics, Diagnostics, And Applications Of Atmospheric Pressure Low Temperature Plasma Sources Used In Plasma Medicine, M. Laroussi

Electrical & Computer Engineering Faculty Publications

Low temperature plasmas have been used in various plasma processing applications for several decades. But it is only in the last thirty years or so that sources generating such plasmas at atmospheric pressure in reliable and stable ways have become more prevalent. First, in the late 1980s, the dielectric barrier discharge was used to generate relatively large volume diffuse plasmas at atmospheric pressure. Then, in the early 2000s, plasma jets that can launch cold plasma plumes in ambient air were developed. Extensive experimental and modeling work was carried out on both methods and much of the physics governing such sources …

Overview Of Game And Content Design For A Mobile Game That Will Prepare Students In Calculus And Physics Prerequisites To The Engineering Curriculum, Katherine Smith, John Shull, Patrick Sean Heaney, Yuzhong Shen, Anthony W. Dean, Jennifer G. Michaeli

VMASC Publications

As part of a research project which assists veterans as they exit the military, complete engineering degrees, and enter the workforce as engineering professionals, a range of serious games for Science, Technology, Engineering, and Mathematics (STEM) education is under development. The current focus of this development is CAPTIVATE, a serious game to assist student veterans in mastering the calculus and physics skills that are necessary prerequisites to the main engineering curriculum. Building on the development and lessons learned from MAVEN, a game developed previously to help student veterans master precalculus skills, the design and initial implementation for CAPTIVATE involves careful …

Scalable And Fully Distributed Localization In Large-Scale Sensor Networks, Miao Jin, Su Xia, Hongyi Wu, Xianfeng David Gu

Electrical & Computer Engineering Faculty Publications

This work proposes a novel connectivity-based localization algorithm, well suitable for large-scale sensor networks with complex shapes and a non-uniform nodal distribution. In contrast to current state-of-the-art connectivity-based localization methods, the proposed algorithm is highly scalable with linear computation and communication costs with respect to the size of the network; and fully distributed where each node only needs the information of its neighbors without cumbersome partitioning and merging process. The algorithm is theoretically guaranteed and numerically stable. Moreover, the algorithm can be readily extended to the localization of networks with a one-hop transmission range distance measurement, and the propagation of …

Supporting Veteran Students Along Engineering Pathways: Faculty, Student, And Researcher Perspectives, Brian J. Novoselich, Janice Leshay Hall, Keith A. Landry, Joyce B. Main, Anthony W. Dean

Engineering Technology Faculty Publications

Student veterans, with their highly technical military training, may help remedy national level gaps in qualified science, technology, engineering, and mathematics (STEM) workers. Recent military education benefits and military end strength reductions have the potential to bolster the nation’s engineering technician, engineering technologist, and engineer (ETETE) workforce. Recent work by the National Science Foundation indicates that supporting veteran students towards ETETE careers involves three key tasks for educators: 1) building early awareness of ETETE pathways; 2) ensuring academic recognition for prior military work experience; and 3) providing seamless support from government agencies, academic institutions, and industry. Many veterans experience an …

Editorial For The Special Issue On Micro/Nano-Chip Electrokinetics, Xiangchun Xuan, Shizhi Qian

Mechanical & Aerospace Engineering Faculty Publications

Micro/nanofluidics-based lab-on-a-chip devices have found extensive applications in the analysis of chemical and biological samples over the past two decades. Electrokinetics is the method of choice in these micro/nano-chips for transporting, manipulating and sensing various analyte species (e.g., ions, molecules, fluids and particles, etc.) [1,2]. This Special Issue in Micromachines is aimed to provide the recent development in the field of Micro/Nano-Chip Electrokinetics. It consists of 15 papers, which cover both fundamentals and applications, original research and reviews

Electromagnetic Design Of A Superconducting Twin Axis Cavity, S. U. De Silva, H. Park, J. R. Delayen, F. Marhauser, A. Hutton

Physics Faculty Publications

The twin-axis cavity is a new kind of rf superconducting cavity that consists of two parallel beam pipes, which can accelerate or decelerate two spatially separated beams in the same cavity. This configuration is particularly effective for high-current beams with low-energy electrons that will be used for bunched beam cooling of high-energy protons or ions. The new cavity geometry was designed to create a uniform accelerating or decelerating fields for both beams by utilizing a TM₁₁₀ dipole mode. This paper presents the design rf optimization of a 1497 MHz twin-axis single-cell cavity, which is currently under fabrication.

Modeling Local Crabbing Dynamics In The Jleic Ion Collider Ring, Salvador Sosa Guitron, Vasiliy Morozov, Jean Delayen

Physics Faculty Publications

The Jefferson Lab Electron-Ion Collider (JLEIC) design considers a 50 mrad crossing angle at the Interaction Point. Without appropriate compensation, this could geometrically reduce the luminosity by an order of magnitude. A local crabbing scheme is implemented to avoid the luminosity loss: crab cavities are placed at both sides of the interaction region to restore a head-on collision scenario. In this contribution, we report on the implementation of a local crabbing scheme in the JLEIC ion ring. The effects of this correction scheme on the stability of proton bunches are analyzed using the particle tracking software elegant.

Aluminum Multicharged Ion Generation From Femtosecond Laser Plasma, Md. Haider A. Shaim, Frederick Guy Wilson, Hani E. Elsayed-Ali

Electrical & Computer Engineering Faculty Publications

Aluminum multicharged ion generation from femtosecond laser ablation is studied. A Ti:sapphire laser (wavelength 800 nm, pulse width ∼100 fs, and maximum laser fluence of 7.6 J/cm²) is used. Ion yield and energy distribution of each charge state are measured. A linear relationship between the ion charge state and the equivalent acceleration energy of the individual ion species is observed and is attributed to the presence of an electric field within the plasma-vacuum boundary that accelerates the ions. The ion energy distribution follows a shifted Coulomb-Boltzmann distribution. For Al¹⁺ and Al²⁺, the ion energy distributions …

Impact Of Rram Read Fluctuations On The Program-Verify Approach, David M. Nminibapiel, Dmitry Veksler, J.-H. Kim, Pragya R. Shrestha, Jason P. Campbell, Jason T. Ryan, Helmut Baumgart, Kin P. Cheung

Electrical & Computer Engineering Faculty Publications

The stochastic nature of the conductive filaments in oxide-based resistive memory (RRAM) represents a sizeable impediment to commercialization. As such, program-verify methodologies are highly alluring. However, it was recently shown that program-verify methods are unworkable due to strong resistance state relaxation after SET/RESET programming. In this paper, we demonstrate that resistance state relaxation is not the main culprit. Instead, it is fluctuation-induced false-reading (triggering) that defeats the program-verify method, producing a large distribution tail immediately after programming. The fluctuation impact on the verify mechanism has serious implications on the overall write/erase speed of RRAM.

Wakefield Analysis Of Superconducting Rf-Dipole Cavities, Subashini De Silva, Jean Delayen

Physics Faculty Publications

RF-dipole crabbing cavities are being considered for a variety of crabbing applications. Some of the applications are the crabbing cavity systems for LHC High Luminosity Upgrade and the proposed Electron-Ion Collider for Jefferson Lab. The design requirements in the current applications require the cavities to incorporate complex damping schemes to suppress the higher order modes that may be excited by the high intensity proton or electron beams traversing through the cavities. The number of cavities required to achieve the desired high transverse voltage, and the complexity in the cavity geometries also contributes to the wakefields generated by beams. This paper …

Trim Tuning Of Sps-Series Dqw Crab Cavity Prototypes, S. Verdú-Andrés, J. Skaritka, Q. Wu, A. Ratti, S. Baurac, C. H. Boulware, T. Grimm, J. Yancey, W. Clemens, E. A. Mcewen, H. Park

Physics Faculty Publications

The final steps in the manufacturing of a superconducting RF cavity involve careful tuning before the final welds to match the target frequency as fabrication tolerances may introduce some frequency deviations. The target frequency is chosen based on analysis of the shifts induced by remaining processing steps including acid etching and cool down. The baseline fabrication of a DQW crab cavity for the High Luminosity LHC (HL-LHC) envisages a first tuning before the cavity subassemblies are welded together. To produce a very accurate final result, subassemblies are trimmed to frequency in the last machining steps, using a clamped cavity assembly …

Computing Spatiotemporal Heat Maps Of Lipid Electropore Formation: A Statistical Approach, Willy Wriggers, Frederica Castellani, Julio A. Kovacs, P. Thomas Vernier

Mechanical & Aerospace Engineering Faculty Publications

We extend the multiscale spatiotemporal heat map strategies originally developed for interpreting molecular dynamics simulations of well-structured proteins to liquids such as lipid bilayers and solvents. Our analysis informs the experimental and theoretical investigation of electroporation, that is, the externally imposed breaching of the cell membrane under the influence of an electric field of sufficient magnitude. To understand the nanoscale architecture of electroporation, we transform time domain data of the coarse-grained interaction networks of lipids and solvents into spatial heat maps of the most relevant constituent molecules. The application takes advantage of our earlier graph-based activity functions by accounting for …

A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Our development of a Fast (Mutual) Information Matching (FIM) of molecular dynamics time series data led us to the general problem of how to accurately estimate the probability density function of a random variable, especially in cases of very uneven samples. Here, we propose a novel Balanced Adaptive Density Estimation (BADE) method that effectively optimizes the amount of smoothing at each point. To do this, BADE relies on an efficient nearest-neighbor search which results in good scaling for large data sizes. Our tests on simulated data show that BADE exhibits equal or better accuracy than existing methods, and visual tests …

Effects Of Light Intensity On Spatial Visualization Ability, Petros J. Katsioloudis ., Mildred Jones

STEMPS Faculty Publications

A plethora of technological advances have happened since artificial illumination was developed by Thomas Edison. Like technology has had an effect in many areas in the modern civilization it also made a difference in the classroom. Nowadays, students can have instruction in classrooms with no external windows, even during gloomy winter or rainy days, and virtually during any hour of the day. Several lightning devices are being used, ranging from energy efficient LEDs to fluorescent lighting. Some forms of lighting methods have been found to be inappropriate for prolonged exposure to the human eye such as various gas-discharge lamps that …

6 Field-Observed Cracking Of Paired Lightweight And Normalweight Concrete Bridge Decks, Tara L. Cavalline, Jeremy T. Calamusa, Amy M. Kitts, Brett Q. Tempest

Engineering Technology Faculty Publications

Research has suggested that conventional lightweight concrete can offer durability advantages due to reduced cracking tendency. Although a number of publications exist providing the results of laboratory-based studies on the durability performance of lightweight concrete (with lightweight coarse aggregate) and internally cured concrete (using prewetted lightweight fine aggregate), far fewer field studies of durability performance of conventional lightweight concrete bridge decks in service have been performed. This study was commissioned to provide insight to a highway agency on whether enhanced durability performance, and therefore reduced maintenance and longer lifecycles, could be anticipated from existing lightweight concrete bridge decks that were …

Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier

Bioelectrics Publications

The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated …

Characterization And Analysis Of Real-Time Capillary Convective Pcr Toward Commercialization, Xianbo Qiu, Shiyin Zhang, Lanju Mei, Di Wu, Ke Li, Shengxiang Ge, Xiangzhong Ye, Ningshao Xia, Michael G. Mauk

Mechanical & Aerospace Engineering Faculty Publications

Almost all the reported capillary convective polymerase chain reaction (CCPCR) systems to date are still limited to research use stemming from unresolved issues related to repeatability, reliability, convenience, and sensitivity. To move CCPCR technology forward toward commercialization, a couple of critical strategies and innovations are discussed here. First, single- and dual-end heating strategies are analyzed and compared between each other. Especially, different solutions for dual-end heating are proposed and discussed, and the heat transfer and fluid flow inside the capillary tube with an optimized dual-end heating strategy are analyzed and modeled. Second, real-time CCPCR is implemented with light-emitting diode and …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …