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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)
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.
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)
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.
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.
Coupling of experimentally validated electroelastic dynamics and mixing rules formulation for macro-fiber composite piezoelectric structures
Shahab, Shima; Erturk, Alper (2016-11-03)
Piezoelectric structures have been used in a variety of applications ranging from vibration control and sensing to morphing and energy harvesting. In order to employ the effective 33-mode of piezoelectricity, interdigitated electrodes have been used in the design of macro-fiber composites which employ piezoelectric fibers with rectangular cross section. In this article, we present an investigation of the two-way electroelastic coupling (in the sense of direct and converse piezoelectric effects) in bimorph cantilevers that employ interdigitated electrodes for 33-mode operation. A distributedparameter electroelastic modeling framework is developed for the elastodynamic scenarios of piezoelectric power generation and dynamic actuation. Mixing rules (i.e. rule of mixtures) formulation is employed to evaluate the equivalent and homogenized properties of macro-fiber composite structures. The electroelastic and dielectric properties of a representative volume element (piezoelectric fiber and epoxy matrix) between two neighboring interdigitated electrodes are then coupled with the global electro-elastodynamics based on the Euler–Bernoulli kinematics accounting for twoway electromechanical coupling. Various macro-fiber composite bimorph cantilevers with different widths are tested for resonant dynamic actuation and power generation with resistive shunt damping. Excellent agreement is reported between the measured electroelastic frequency response and predictions of the analytical framework that bridges the continuum electro-elastodynamics and mixing rules formulation.
Debonding of confined elastomeric layer using cohesive zone model
Mukherjee, Bikramjit; Dillard, David A.; Moore, Robert Bowen; Batra, Romesh C. (Elsevier, 2016-04-01)
Wavy or undulatory debonding is often observed when a confined/sandwiched elastomeric layer is pulled off from a stiff adherend. Here we analyze this debonding phenomenon using a cohesive zone model (CZM). Using stability analysis of linear equations governing plane strain quasi-static deformations of an elastomer, we find (i) a non-dimensional number relating the elastomer layer thickness, h, the long term Young's modulus, E_∞, of the interlayer material, the peak traction, T_c, in the CZM bilinear tractionseparation (TS) relation, and the fracture energy, G_c, of the interface between the adherend and the elastomer layer, and (ii) the critical value of this number that provides a necessary condition for undulations to occur during debonding. For the elastomer modeled as a linear viscoelastic material with the shear modulus given by a Prony series and a rate-independent bilinear TS relation in the CZM, the stability analysis predicts that a necessary condition for a wavy solution is that T_c²h=G_cE_∞ exceed 4:15. This is supported by numerically solving governing equations by the finite element method (FEM). Lastly, we use the FEM to study three-dimensional deformations of the peeling (induced by an edge displacement) of a flexible plate from a thin elastomeric layer perfectly bonded to a rigid substrate. These simulations predict progressive debonding with a fingerlike front for sufficiently confined interlayers when the TS parameters satisfy a constraint similar to that found from the stability analysis of the plane strain problem.
Development of a Concussion Risk Function for a Youth Population Using Head Linear and Rotational Acceleration
Campolettano, Eamon T.; Gellner, Ryan A.; Smith, Eric P.; Bellamkonda, Srinidhi; Tierney, Casey T.; Crisco, Joseph J.; Jones, Derek A.; Kelley, Mireille E.; Urban, Jillian E.; Stitzel, Joel D.; Genemaras, Amaris; Beckwith, Jonathan G.; Greenwald, Richard M.; Maerlender, Arthur C.; Brolinson, Per Gunnar; Duma, Stefan M.; Rowson, Steven (Springer, 2019-10-28)
Physical differences between youth and adults, which include incomplete myelination, limited neck muscle development, and a higher head-body ratio in the youth population, likely contribute towards the increased susceptibility of youth to concussion. Previous research efforts have considered the biomechanics of concussion for adult populations, but these known age-related differences highlight the necessity of quantifying the risk of concussion for a youth population. This study adapted the previously developed Generalized Acceleration Model for Brian Injury Threshold (GAMBIT) that combines linear and rotational head acceleration to model the risk of concussion for a youth population with the Generalized Acceleration Model for Concussion in Youth (GAM-CY). Survival analysis was used in conjunction with head impact data collected during participation in youth football to model risk between individuals who sustained medically-diagnosed concussions (n = 15). Receiver operator characteristic curves were generated for peak linear acceleration, peak rotational acceleration, and GAM-CY, all of which were observed to be better injury predictors than random guessing. GAM-CY was associated with an area under the curve of 0.89 (95% confidence interval: 0.82–0.95) when all head impacts experienced by the concussed players were considered. Concussion tolerance was observed to be lower for youth athletes, with average peak linear head acceleration of 62.4 ± 29.7 g compared to 102.5 ± 32.7 g for adults and average peak rotational head acceleration of 2609 ± 1591 rad/s2 compared to 4412 ± 2326 rad/s2. These data provide further evidence of age-related differences in concussion tolerance and may be used for the development of youth-specific protective designs.
Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium
Greer-Short, Amara D.; Poelzing, Steven (Frontiers, 2015-02-18)
Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 +/- 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34 degrees C) produced significantly earlier excited beats (53 +/- 14%, n = 5) with wider QRS durations (58 +/- 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 mu M) produced the most excited beats with significantly earlier RCL (44 +/- 3.2%, n = 6) and wider QRS (60 +/- 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 +/- 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 +/- 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.
Drug Delivery Based on Swarm Microrobots
Banharnsakun, A.; Achalakul, T.; Batra, Romesh C. (2016-06)
Edge Debonding in Peeling of a Thin Flexible Plate From an Elastomer Layer: A Cohesive Zone Model Analysis
Mukherjee, Bikramjit; Batra, Romesh C.; Dillard, David A. (2016-11-07)
A cohesive zone modeling (CZM) approach with a bilinear traction-separation relation is used to study the peeling of a thin overhanging plate from the edge of an incompressible elastomeric layer bonded firmly to a stationary rigid base. The deformations are approximated as plane strain and the materials are assumed to be linearly elastic, homogeneous, and isotropic. Furthermore, governing equations for the elastomer deformations are simplified using the lubrication theory approximations, and those of the plate with the Kirchhoff–Love theory. It is found that the peeling is governed by a single nondimensional number defined in terms of the interfacial strength, the interface fracture energy, the plate bending rigidity, the elastomer shear modulus, and the elastomeric layer thickness. An increase in this nondimensional number monotonically increases the CZ size ahead of the debond tip, and the pull-off force transitions from a fracture energy to strength dominated regime. This finding is supported by the results of the boundary value problem numerically studied using the finite element method. Results reported herein could guide elastomeric adhesive design for load capacity and may help ascertain test configurations for extracting the strength and the fracture energy of an interface from test data.
The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial
Ghatnekar, Gautam S.; Grek, Christina L.; Armstrong, David G.; Desai, Sanjay C.; Gourdie, Robert G. (2015-01)
The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.
Effect of confinement and interfacial adhesion on peeling of a flexible plate from an elastomeric layer
Mukherjee, Bikramjit; Batra, Romesh C.; Dillard, David A. (2016-09)
The finite element method and a cohesive zone model are used to analyze plane strain interfacial debonding of an elastomeric layer from an overhanging deformable plate when it is peeled off by applying a normal displacement at the edge of the overhang. The commercial software, ABAQUS, is employed in this work that is focused on understanding the collective role of the following two non-dimensional parameters: (i) the confinement parameter, α, defined in terms of the flexural rigidity of the plate, and the modulus and the thickness of the interlayer, and (ii) the adhesion parameter, φ, defined in terms of the cohesive zone parameters and the modulus to thickness ratio of the interlayer. The interfacial adhesion is characterized by a bilinear traction-separation (TS) relation. Numerical experiments reveal that when α is greater than αc , damage initiates at an interior point on the interface and at the interface corner on the traction-free edge irrespective of the value of φ. However, φ must be greater than φc for the debonding to become wavy/undulatory. The critical value, φc , of the adhesion parameter agrees with the necessary condition found in our previous work on debonding of an elastomeric layer from a rigid block when it is uniformly pulled outward. For α < αc , damage/debonding initiates only from the interface corner, and no wavy debonding ensues. The peak peeling force prior to the initiation of an internal debond is found to be a monotonically increasing function of φ/ α, suggesting its potential use as a design variable and as a guide for determining the TS parameters. Results of a few additional numerical experiments in which the elastomeric layer can debond from both adherends provide insights into designing a demolding process for a sandwiched elastomeric layer.
Effect of Covalent Functionalization on Young’s Modulus of a Single-Wall Carbon Nanotube
Shah, Priyal H.; Batra, Romesh C. (Springer, 2014)
Effective utilization of carbon nanotubes (CNTs) as reinforcements in composites necessitates good interfacial bonding with the surround matrix material. The covalent functionalization of CNTs is an effective method to enhance this bonding. However, covalent bonds introduced by a functional group may alter the pristine structure of the CNT and lower its mechanical properties. Here we study the effect of hydrogen (–H), hydroxyl (–OH), carboxyl (–COOH), and amine (–NH2) functionalization on Young’s modulus of a single-wall CNT (SWCNT) using molecular mechanics (MM) simulations with the MM3 potential and the software TINKER. Both pristine and functionalized SWCNTs have been deformed in simple tension. From the strain energy of deformation vs. the axial strain curves, the value of Young’s modulus has been derived as a function of the functionalization group and the amount of functionalization. It is found that Young’s modulus decreases by about 30 % with 20 % of functionalization, the reduction is essentially proportional to the increase in the percentage of the functionalization material and is nearly the same for each of the four functional groups studied.

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