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Ablation outcome of irreversible electroporation on potato monitored by impedance spectrum under multi-electrode system
Zhao, Yajun; Liu, Hongmei; Bhonsle, Suyashree P.; Wang, Yilin; Davalos, Rafael V.; Yao, Chenguo (2018-09-20)
Background Irreversible electroporation (IRE) therapy relies on pulsed electric fields to non-thermally ablate cancerous tissue. Methods for evaluating IRE ablation in situ are critical to assessing treatment outcome. Analyzing changes in tissue impedance caused by electroporation has been proposed as a method for quantifying IRE ablation. In this paper, we assess the hypothesis that irreversible electroporation ablation outcome can be monitored using the impedance change measured by the electrode pairs not in use, getting more information about the ablation size in different directions. Methods Using a square four-electrode configuration, the two diagonal electrodes were used to electroporate potato tissue. Next, the impedance changes, before and after treatment, were measured from different electrode pairs and the impedance information was extracted by fitting the data to an equivalent circuit model. Finally, we correlated the change of impedance from various electrode pairs to the ablation geometry through the use of fitted functions; then these functions were used to predict the ablation size and compared to the numerical simulation results. Results The change in impedance from the electrodes used to apply pulses is larger and has higher deviation than the other electrode pairs. The ablation size and the change in resistance in the circuit model correlate with various linear functions. The coefficients of determination for the three functions are 0.8121, 0.8188 and 0.8691, respectively, showing satisfactory agreement. The functions can well predict the ablation size under different pulse numbers, and in some directions it did even better than the numerical simulation method, which used different electric field thresholds for different pulse numbers. Conclusions The relative change in tissue impedance measured from the non-energized electrodes can be used to assess ablation size during treatment with IRE according to linear functions.
Acceleration Feedback-Based Active and Semi-Active Seismic Response Control of Rail-Counterweight Systems of Elevators
Singh, Rildova; Singh, Mahendra P. (Hindawi, 2005-01-01)
Based on the observations in the past earthquake events, the traction elevators in buildings are known to be vulnerable to earthquake induced ground motions. Among several components of an elevator, the counterweight being heaviest is also known to be more susceptible than others. The inertial effects of the counterweight can overstress the guide rails on which it moves. Here we investigate to use the well-known acceleration feedback-based active and semi-active control methods to reduce stresses in the rails. The only way a control action can be applied to a moving counterweight-rail system is through a mass damper placed in the plane of the counterweight. For this, a part of the counterweight mass can be configured as a mass damper attached to a small actuator for an active scheme or to a magneto-rheological damper for a semi-active scheme. A comprehensive numerical study is conducted to evaluate the effectiveness of the proposed configuration of control system. It is observed that the two control schemes are effective in reducing the stress response by about 20 to 25% and improve the system fragility over a good range of seismic intensities.
Allele-specific methylation in the FADS genomic region in DNA from human saliva, CD4+ cells, and total leukocytes
Rahbar, Elaheh; Waits, Charlotte M. K.; Kirby, Edward H.; Miller, Leslie R.; Ainsworth, Hannah C.; Cui, Tao; Sergeant, Susan; Howard, Timothy D.; Langefeld, Carl D.; Chilton, Floyd H. (2018-04-06)
Background Genetic variants within the fatty acid desaturase (FADS) gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the FADS cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the FADS region in human liver tissues. Given that epigenetic signatures are tissue-specific, we aimed to evaluate the methylation status and ASM associations between rs174537 and DNA methylation obtained from human saliva, CD4+ cells and total leukocytes derived from whole blood. The goals were to (1) determine if DNA methylation from these peripheral samples would display similar ASM trends as previously observed in human liver tissues and (2) evaluate the associations between DNA methylation and circulating LC-PUFAs. Results DNA methylation at six CpG sites spanning FADS1 and FADS2 promoter regions and a putative FADS enhancer region were determined in two Caucasian cohorts of healthy volunteers: leukocytes in cohort 1 (n = 89, median age = 43, 35% male) and saliva and CD4+ cells in cohort 2 (n = 32, median age = 41, 41% male). Significant ASM between rs174537 and DNA methylation at three CpG sites located in the FADS2 promoter region (i.e., chr11:61594865, chr11:61594876, chr11:61594907) and one CpG site in the putative enhancer region (chr11:61587979) were observed with leukocytes. In CD4+ cells, significant ASM was observed at CpG sites chr11:61594876 and chr11:61584894. Genotype at rs174537 was significantly associated with DNA methylation from leukocytes. Similar trends were observed with CD4+ cells, but not with saliva. DNA methylation from leukocytes and CD4+ cells also significantly correlated with circulating omega-6 LC-PUFAs. Conclusions We observed significant ASM between rs174537 and DNA methylation at key regulatory regions in the FADS region from leukocyte and CD4+ cells. DNA methylation from leukocytes also correlated with circulating omega-6 LC-PUFAs. These results support the use of peripheral whole blood samples, with leukocytes showing the most promise for future nutrigenomic studies evaluating epigenetic modifications affecting LC-PUFA biosynthesis in humans.
Analysis of 2-dimensional transient problems for linear elastic and piezoelectric structures using the consecutive-interpolation quadrilateral element (CQ4)
Tinh, Q. B.; Du, D. N.; Zhang, X.; Hirose, S.; Batra, Romesh C. (Elsevier, 2016-07-01)
Anti-Swing Control of Gantry and Tower Cranes Using Fuzzy and Time-Delayed Feedback with Friction Compensation
Omar, Hanafy M.; Nayfeh, Ali H. (Hindawi, 2005-01-01)
We designed a feedback controller to automate crane operations by controlling the load position and its swing. First, a PD tracking controller is designed to follow a prescribed trajectory. Then, another controller is added to the control loop to damp the load swing. The anti-swing controller is designed based on two techniques: a time-delayed feedback of the load swing angle and an anti-swing fuzzy logic controller (FLC). The rules of the FLC are generated by mapping the performance of the time-delayed feedback controller. The same mapping method used for generating the rules can be applied to mimic the performance of an expert operator. The control algorithms were designed for gantry cranes and then extended to tower cranes by considering the coupling between the translational and rotational motions. Experimental results show that the controller is effective in reducing load oscillations and transferring the load in a reasonable time. To experimentally validate the theory, we had to compensate for friction. To this end, we estimated the friction and then applied a control action to cancel it. The friction force was estimated by assuming a mathematical model and then estimating the model coefficients using an off-line identification technique, the method of least squares (LS).
Application of sub-micrometer vibrations to mitigate bacterial adhesion
Paces, Will R.; Holmes, Hal R.; Vlaisavljevich, Eli; Snyder, Katherine L.; Tan, Ee Lim; Rajachar, Rupak M.; Ong, Keat Ghee (2014-03-11)
As a prominent concern regarding implantable devices, eliminating the threat of opportunistic bacterial infection represents a significant benefit to both patient health and device function. Current treatment options focus on chemical approaches to negate bacterial adhesion, however, these methods are in some ways limited. The scope of this study was to assess the efficacy of a novel means of modulating bacterial adhesion through the application of vibrations using magnetoelastic materials. Magnetoelastic materials possess unique magnetostrictive property that can convert a magnetic field stimulus into a mechanical deformation. In vitro experiments demonstrated that vibrational loads generated by the magnetoelastic materials significantly reduced the number of adherent bacteria on samples exposed to Escherichia coli, Staphylococcus epidermidis and Staphylococcus aureus suspensions. These experiments demonstrate that vibrational loads from magnetoelastic materials can be used as a post-deployment activated means to deter bacterial adhesion and device infection.
Assessment of Deep Partial Thickness Burn Treatment with Keratin Biomaterial Hydrogels in a Swine Model
Poranki, D.; Goodwin, C.; Van Dyke, M. (Hindawi, 2016-01-01)
Partial thickness burns can advance to full thickness after initial injury due to inadequate tissue perfusion and increased production of inflammatory cytokines, which has been referred to as burn wound progression. In previous work, we demonstrated that a keratin biomaterial hydrogel appeared to reduce burn wound progression. In the present study, we tested the hypothesis that a modified keratin hydrogel could reduce burn wound progression and speed healing. Standardized burn wounds were created in Yorkshire swine and treated within 30 minutes with keratin hydrogel (modified and unmodified), collagen hydrogel, or silver sulfadiazine (SSD). Digital images of each wound were taken for area measurements immediately prior to cleaning and dressing changes. Wound tissue was collected and assessed histologically at several time points. Wound area showed a significant difference between hydrogels and SSD groups, and rates of reepithelialization at early time points showed an increase when keratin treatment was used compared to both collagen and SSD. A linear regression model predicted a time to wound closure of approximately 25 days for keratin hydrogel while SSD treatment required 35 days. There appeared to be no measurable differences between the modified and unmodified formulations of keratin hydrogels.
Axisymmetric Natural Frequencies of Statically Loaded Annular Plates
Abdel-Rahman, Eihab M.; Faris, Waleed F.; Nayfeh, Ali H. (Hindawi, 2003-01-01)
We present a numerical procedure to solve the axisymmetric vibration problem of statically loaded annular plates. We use the von Kármán nonlinear plate model to account for large deformations and study the effect of static deflections on the natural frequencies and mode shapes for six combinations of boundary conditions. The shooting method is used to solve the resulting eigenvalue problem. Our results show that static deformations have a significant effect on the natural frequencies and small effect on the mode shapes of the plate. Further, the results show that the presence of in-plane stresses has a significant effect on the natural frequencies.
Bare-hand volume cracker for raw volume data analysis
Socha, John J.; Laha, Bireswar; Bowman, Douglas A. (2016-09-28)
Analysis of raw volume data generated from different scanning technologies faces a variety of challenges, related to search, pattern recognition, spatial understanding, quantitative estimation, and shape description. In a previous study, we found that the volume cracker (VC) 3D interaction (3DI) technique mitigated some of these problems, but this result was from a tethered glove-based system with users analyzing simulated data. Here, we redesigned the VC by using untethered bare-hand interaction with real volume datasets, with a broader aim of adoption of this technique in research labs. We developed symmetric and asymmetric interfaces for the bare-hand VC (BHVC) through design iterations with a biomechanics scientist. We evaluated our asymmetric BHVC technique against standard 2D and widely used 3DI techniques with experts analyzing scanned beetle datasets. We found that our BHVC design significantly outperformed the other two techniques. This study contributes a practical 3DI design for scientists, documents lessons learned while redesigning for bare-hand trackers and provides evidence suggesting that 3DI could improve volume data analysis for a variety of visual analysis tasks. Our contribution is in the realm of 3D user interfaces tightly integrated with visualization for improving the effectiveness of visual analysis of volume datasets. Based on our experience, we also provide some insights into hardware-agnostic principles for design of effective interaction techniques.
Binding afﬁnity between small molecules in solvent and polymer ﬁlm using molecular dynamics simulations
Batra, Romesh C. (2017)
Blood Vessel Patterning on Retinal Astrocytes Requires Endothelial Flt-1 (VEGFR-1)
Chappell, John C.; Darden, Jordan; Payne, Laura Beth; Fink, Kathryn; Bautch, Victoria L. (MDPI, 2019-09-07)
Feedback mechanisms are critical components of many pro-angiogenic signaling pathways that keep vessel growth within a functional range. The Vascular Endothelial Growth Factor-A (VEGF-A) pathway utilizes the decoy VEGF-A receptor Flt-1 to provide negative feedback regulation of VEGF-A signaling. In this study, we investigated how the genetic loss of flt-1 differentially affects the branching complexity of vascular networks in tissues despite similar effects on endothelial sprouting. We selectively ablated flt-1 in the post-natal retina and found that maximum induction of flt-1 loss resulted in alterations in endothelial sprouting and filopodial extension, ultimately yielding hyper-branched networks in the absence of changes in retinal astrocyte architecture. The mosaic deletion of flt-1 revealed that sprouting endothelial cells flanked by flt-1⁻^/− regions of vasculature more extensively associated with underlying astrocytes and exhibited aberrant sprouting, independent of the tip cell genotype. Overall, our data support a model in which tissue patterning features, such as retinal astrocytes, integrate with flt-1-regulated angiogenic molecular and cellular mechanisms to yield optimal vessel patterning for a given tissue.
Buckling of single-walled carbon nanotubes using two criteria
Gupta, Shakti S.; Agrawal, Pranav; Batra, Romesh C. (American Institute of Physics, 2016-06-28)
Classical and adaptive control of ex vivo skeletal muscle contractions using Functional Electrical Stimulation (FES)
Cienfuegos, Paola Jaramillo; Shoemaker, Adam; Grange, Robert W.; Abaid, Nicole; Leonessa, Alexander (PLOS, 2017-03-08)
Functional Electrical Stimulation is a promising approach to treat patients by stimulating the peripheral nerves and their corresponding motor neurons using electrical current. This technique helps maintain muscle mass and promote blood flow in the absence of a functioning nervous system. The goal of this work is to control muscle contractions from FES via three different algorithms and assess the most appropriate controller providing effective stimulation of the muscle. An open-loop system and a closed-loop system with three types of model-free feedback controllers were assessed for tracking control of skeletal muscle contractions: a Proportional-Integral (PI) controller, a Model Reference Adaptive Control algorithm, and an Adaptive Augmented PI system. Furthermore, a mathematical model of a muscle-mass-spring system was implemented in simulation to test the open-loop case and closed-loop controllers. These simulations were carried out and then validated through experiments ex vivo. The experiments included muscle contractions following four distinct trajectories: a step, sine, ramp, and square wave. Overall, the closed-loop controllers followed the stimulation trajectories set for all the simulated and tested muscles. When comparing the experimental outcomes of each controller, we concluded that the Adaptive Augmented PI algorithm provided the best closed-loop performance for speed of convergence and disturbance rejection.
Compressive Mechanical Properties of Porcine Brain: Experimentation and Modeling of the Tissue Hydration Effects
Prabhu, Raj K.; Begonia, Mark T.; Whittington, Wilburn R.; Murphy, Michael A.; Mao, Yuxiong; Liao, Jun; Williams, Lakiesha N.; Horstemeyer, Mark F.; Sheng, Jianping (MDPI, 2019-05-07)
Designing protective systems for the human head—and, hence, the brain—requires understanding the brain’s microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on the brain’s biomechanics. Here, native ‘wet’ brain samples contained ~80% (mass/mass) water content and ‘dry’ brain samples contained ~0% (mass/mass) water content. First, the wet brain incurred a large initial peak stress that was not exhibited by the dry brain. Second, stress levels for the dry brain were greater than the wet brain. Third, the dry brain stress–strain behavior was characteristic of ductile materials with a yield point and work hardening; however, the wet brain showed a typical concave inflection that is often manifested by polymers. Finally, finite element analysis (FEA) of the brain’s high strain rate response for samples with various proportions of water and dry brain showed that water played a major role in the initial hardening trend. Therefore, hydration level plays a key role in brain tissue micromechanics, and the incorporation of this hydration effect on the brain’s mechanical response in simulated injury scenarios or virtual human-centric protective headgear design is essential.
Computational tools for inversion and uncertainty estimation in respirometry
Cho, Taewon; Pendar, Hodjat; Chung, Julianne (PLoS, 2021-05-21)
In many physiological systems, real-time endogeneous and exogenous signals in living organisms provide critical information and interpretations of physiological functions; however, these signals or variables of interest are not directly accessible and must be estimated from noisy, measured signals. In this paper, we study an inverse problem of recovering gas exchange signals of animals placed in a flow-through respirometry chamber from measured gas concentrations. For large-scale experiments (e.g., long scans with high sampling rate) that have many uncertainties (e.g., noise in the observations or an unknown impulse response function), this is a computationally challenging inverse problem. We first describe various computational tools that can be used for respirometry reconstruction and uncertainty quantification when the impulse response function is known. Then, we address the more challenging problem where the impulse response function is not known or only partially known. We describe nonlinear optimization methods for reconstruction, where both the unknown model parameters and the unknown signal are reconstructed simultaneously. Numerical experiments show the benefits and potential impacts of these methods in respirometry.
Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1
Rhett, J. Matthew; Jourdan, L. Jane; Gourdie, Robert G. (2011-05)
Connexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus of Cx43, and we have previously shown that inhibition of the Cx43/ZO-1 interaction increases GJ size by 48 h. Here we demonstrated that increases in GJ aggregation occur within 2 h (∼Cx43 half-life) following disruption of Cx43/ZO-1. Immunoprecipitation and Duolink protein-protein interaction assays indicated that inhibition targets ZO-1 binding with Cx43 in GJs as well as connexons in an adjacent domain that we term the "perinexus." Consistent with GJ size increases being matched by decreases in connexons, inhibition of Cx43/ZO-1 reduced the extent of perinexal interaction, increased the proportion of connexons docked in GJs relative to undocked connexons in the plasma membrane, and increased GJ intercellular communication while concomitantly decreasing hemichannel-mediated membrane permeance in contacting, but not noncontacting, cells. ZO-1 small interfering RNA and overexpression experiments verified that loss and gain of ZO-1 function govern the transition of connexons into GJs. It is concluded that ZO-1 regulates the rate of undocked connexon aggregation into GJs, enabling dynamic partitioning of Cx43 channel function between junctional and proximal nonjunctional domains of plasma membrane.
Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration
Zhang, Ao; Hitomi, Masahiro; Bar-Shain, Noah; Dalimov, Zafardjan; Ellis, Leigh; Velpula, Kiran K.; Fraizer, Gail C.; Gourdie, Robert G.; Lathia, Justin D. (2015-05-10)
Impaired expression of connexins, the gap junction subunits that facilitate direct cell-cell communication, have been implicated in prostate cancer growth. To elucidate the crucial role of connexins in prostate cancer progression, we performed a systematic quantitative RT-PCR screening of connexin expression in four representative prostate cancer cell lines across the spectrum of malignancy. Transcripts of several connexin subunits were detected in all four cell lines, and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in cells with increased metastatic potential. Analysis of gap-junction-mediated intercellular communication revealed homocellular coupling in PC-3 cells, which had the highest C x 43 expression, with minimal coupling in LNCaP cells where C x 43 expression was very low. Treatment with the gap junction inhibitor carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth, suggesting that growth is independent of functional gap junctions. PC-3 cells with C x 43 expression reduced by shRNA showed decreased migration in monolayer wound healing assay, as well as decreased transwell invasion capacities when compared to control cells expressing non-targeting shRNA. These results, together with the correlation between C x 43 expression levels and the metastatic capacity of the cell lines, suggest a role of C x 43 in prostate cancer invasion and metastasis.
Constitutive Relation for Large Deformations of Fiber-Reinforced Rubberlike Materials with Different Response in Tension and Compression
Li, Q.; Dillard, David A.; Batra, Romesh C. (2016-01)
Fiber-reinforced rubberlike materials commonly used in tires undergo large deformations and exhibit different responses in tension and compression along the fiber direction. Assuming that the response of a fiber-reinforced rubberlike material can be modeled as transversely isotropic with the fiber direction as the axis of transverse isotropy, we express the stored energy function in terms of the five invariants of the right Cauchy-Green strain tensor and account for different response in tension and compression along the fiber direction. The constitutive relation accounts for both material and geometric nonlinearities and incorporates effects of the fifth strain invariant, I5. It has been shown by Merodio and Ogden that in shear dominated deformations, I5 makes a significant contribution to the stress-strain curve. We have implemented the proposed constitutive relation in the commercial software, LS-DYNA. The numerical solutions of a few boundary value problems studied here agree with their analytical solutions derived by using Ericksen’s inverse approach, in which part of the solution is assumed and unknowns in the presumed solution are found by analyzing the pertinent boundary value problem. However, computed results have not been compared with experimental findings. When test data become available, one can modify the form of the strain energy density and replace the proposed constitutive relation by the new one in LS-DYNA.
Control of Limit Cycle Oscillations of a Two-Dimensional Aeroelastic System
Ghommem, Mehdi; Nayfeh, Ali H.; Hajj, Muhammad R. (Hindawi Publishing Corporation, 2010)
Linear and nonlinear static feedback controls are implemented on a nonlinear aeroelastic system that consists of a rigid airfoil supported by nonlinear springs in the pitch and plunge directions and subjected to nonlinear aerodynamic loads. The normal form is used to investigate the Hopf bifurcation that occurs as the freestream velocity is increased and to analytically predict the amplitude and frequency of the ensuing limit cycle oscillations (LCO). It is shown that linear control can be used to delay the flutter onset and reduce the LCO amplitude. Yet, its required gains remain a function of the speed. On the other hand, nonlinear control can be efficiently implemented to convert any subcritical Hopf bifurcation into a supercritical one and to significantly reduce the LCO amplitude.
Control of Rotary Cranes Using Fuzzy Logic
Al-mousa, Amjed A.; Nayfeh, Ali H.; Kachroo, Pushkin (Hindawi, 2003-01-01)
Rotary cranes (tower cranes) are common industrial structures that are used in building construction, factories, and harbors. These cranes are usually operated manually. With the size of these cranes becoming larger and the motion expected to be faster, the process of controlling them has become difficult without using automatic control methods. In general, the movement of cranes has no prescribed path. Cranes have to be run under different operating conditions, which makes closed-loop control attractive.In this work a fuzzy logic controller is introduced with the idea of “split-horizon”; that is, fuzzy inference engines (FIE) are used for tracking the position and others are used for damping the load oscillations. The controller consists of two independent sub-controllers: radial and rotational. Each of these controllers has two fuzzy inference engines (FIE). Computer simulations are used to verify the performance of the controller. Three simulation cases are presented. In the first case, the crane is operated in the gantry (radial) mode in which the trolley moves along the jib while the jib is fixed. In the second case (rotary mode), the trolley moves along the jib and the jib rotates. In the third case, the trolley and jib are fixed while the load is given an initial disturbance. The results from the simulations show that the fuzzy controller is capable of keeping the load-oscillation angles small throughout the maneuvers while completing the maneuvers in relatively reasonable times.

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