Department of Biomedical Engineering and Mechanics

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A collaboration between School of Biomedical Engineering and Sciences and the Department of Engineering Science and Mechanics to form the Department of Biomedical Engineering and Mechanics.

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2023 Engineering Mechanics Research Symposium
(Virginia Tech, 2023-03)
The annual Engineering Mechanics Spring Symposium featured lecture and poster presentations from both students and faculty members.
2D or 3D? How cell motility measurements are conserved across dimensions in vitro and translate in vivo
Galarza, Sualyneth; Kim, Hyuna; Atay, Naciye; Peyton, Shelly R.; Munson, Jennifer M. (2019-11-19)
Cell motility is a critical aspect of several processes, such as wound healing and immunity; however, it is dysregulated in cancer. Current limitations of imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D (two-dimensional) and 3D (three-dimensional) tissue model systems in which to study cell motility in vitro, with the aim of mimicking elements of the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries or systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, metrics are conserved across systems. To our surprise, only one metric of cell movement on 2D surfaces significantly and positively correlates with cell migration in 3D environments (percent migrating cells), and cell invasion in 3D has a weak, negative correlation with glioblastoma invasion in vivo. Finally, to compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
A 3-D Finite-Element Minipig Model to Assess Brain Biomechanical Responses to Blast Exposure
Sundaramurthy, Aravind; Kote, Vivek Bhaskar; Pearson, Noah; Boiczyk, Gregory M.; McNeil, Elizabeth M.; Nelson, Allison J.; Subramaniam, Dhananjay Radhakrishnan; Rubio, Jose E.; Monson, Kenneth; Hardy, Warren N.; VandeVord, Pamela J.; Unnikrishnan, Ginu; Reifman, Jaques (Frontiers, 2021-12-17)
Despite years of research, it is still unknown whether the interaction of explosion-induced blast waves with the head causes injury to the human brain. One way to fill this gap is to use animal models to establish “scaling laws” that project observed brain injuries in animals to humans. This requires laboratory experiments and high-fidelity mathematical models of the animal head to establish correlates between experimentally observed blast-induced brain injuries and model-predicted biomechanical responses. To this end, we performed laboratory experiments on Göttingen minipigs to develop and validate a three-dimensional (3-D) high-fidelity finite-element (FE) model of the minipig head. First, we performed laboratory experiments on Göttingen minipigs to obtain the geometry of the cerebral vasculature network and to characterize brain-tissue and vasculature material properties in response to high strain rates typical of blast exposures. Next, we used the detailed cerebral vasculature information and species-specific brain tissue and vasculature material properties to develop the 3-D high-fidelity FE model of the minipig head. Then, to validate the model predictions, we performed laboratory shock-tube experiments, where we exposed Göttingen minipigs to a blast overpressure of 210 kPa in a laboratory shock tube and compared brain pressures at two locations. We observed a good agreement between the model-predicted pressures and the experimental measurements, with differences in maximum pressure of less than 6%. Finally, to evaluate the influence of the cerebral vascular network on the biomechanical predictions, we performed simulations where we compared results of FE models with and without the vasculature. As expected, incorporation of the vasculature decreased brain strain but did not affect the predictions of brain pressure. However, we observed that inclusion of the cerebral vasculature in the model changed the strain distribution by as much as 100% in regions near the interface between the vasculature and the brain tissue, suggesting that the vasculature does not merely decrease the strain but causes drastic redistributions. This work will help establish correlates between observed brain injuries and predicted biomechanical responses in minipigs and facilitate the creation of scaling laws to infer potential injuries in the human brain due to exposure to blast waves.
3D X-ray analysis of the subterranean burrowing depth and pupal chamber size of Laricobius (Coleoptera: Derodontidae), a specialist predator of Adelges tsugae (Hemiptera: Adelgidae)
Hillen, Ashleigh P.; Foley, Jeremiah R.; Salcedo, Mary K.; Socha, John J.; Salom, Scott M. (Oxford University Press, 2023-05-01)
The non-native hemlock woolly adelgid (HWA), Adelges tsugae Annand (Hemiptera: Adelgidae), has caused a significant decline of eastern hemlock, Tsuga canadensis L. (Pinales: Pinaceae), and Carolina hemlock, Tsuga caroliniana Engelmann (Pinales: Pinaceae), in eastern North America. Biological control of HWA has focused on the use of 2 Laricobius spp. (Coleoptera: Derodontidae), natural predators of HWA, which require arboreal and subterranean life phases to complete their development. In its subterranean phase, Laricobius spp. are subject to abiotic factors including soil compaction or soil-applied insecticides used to protect hemlock from HWA. This study used 3D X-ray microcomputed tomography (micro-CT) to identify the depth at which Laricobius spp. burrows during its subterranean lifecycle, characterize pupal chamber volume, and determine whether soil compaction had a significant effect on these variables. The mean burrowing depth in the soil of individuals was 27.0 mm ± 14.8 (SD) and 11.4 mm ± 11.8 (SD) at compaction levels of 0.36 and 0.54 g/ cm3, respectively. The mean pupal chamber volume was 11.15 mm3 ± 2.8 (SD) and 7.65 mm3 ± 3.5 (SD) in soil compacted at 0.36 and 0.54 g/cm3, respectively. These data show that soil compaction influences burrowing depth and pupal chamber size for Laricobius spp.This information will help us better identify the effect of soil-applied insecticide residues on estivating Laricobius spp. and soil-applied insecticide residues in the field. Additionally, these results demonstrate the utility of 3D micro-CT in assessing subterranean insect activity in future studies.
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.
Ablative and Immunostimulatory Effects of Histotripsy Ablation in a Murine Osteosarcoma Model
Hay, Alayna N.; Imran, Khan Mohammad; Hendricks-Wenger, Alissa; Gannon, Jessica M.; Sereno, Jacqueline; Simon, Alex; Lopez, Victor A.; Coutermarsh-Ott, Sheryl; Vlaisavljevich, Eli; Allen, Irving C.; Tuohy, Joanne L. (MDPI, 2023-10-09)
Background: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in humans, primarily affecting children and adolescents. Significant advancements in treatment options for OS have not occurred in the last several decades, and the prognosis remains grim with only a 70% rate of 5-year survival. The objective of this study was to investigate the focused ultrasound technique of histotripsy as a novel, noninvasive treatment option for OS. Methods: We utilized a heterotopic OS murine model to establish the feasibility of ablating OS tumors with histotripsy in a preclinical setting. We investigated the local immune response within the tumor microenvironment (TME) via immune cell phenotyping and gene expression analysis. Findings: We established the feasibility of ablating heterotopic OS tumors with ablation characterized microscopically by loss of cellular architecture in targeted regions of tumors. We observed greater populations of macrophages and dendritic cells within treated tumors and the upregulation of immune activating genes 72 h after histotripsy ablation. Interpretation: This study was the first to investigate histotripsy ablation for OS in a preclinical murine model, with results suggesting local immunomodulation within the TME. Our results support the continued investigation of histotripsy as a novel noninvasive treatment option for OS patients to improve clinical outcomes and patient prognosis.
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.
Accounting for Variance in Concussion Tolerance Between Individuals: Comparing Head Accelerations Between Concussed and Physically Matched Control Subjects
Rowson, Steven; Campolettano, Eamon T.; Duma, Stefan M.; Stemper, Brian D.; Shah, Alok S.; Harezlak, Jaroslaw; Riggen, Larry D.; Mihalik, Jason P.; Guskiewicz, Kevin M.; Giza, Christopher C.; Brooks, M. Alison; Cameron, Kenneth L.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael A. (Springer, 2019-10-01)
Researchers have been collecting head impact data from instrumented football players to characterize the biomechanics of concussion for the past 15 years, yet the link between biomechanical input and clinical outcome is still not well understood. We have previously shown that even though concussive biomechanics might be unremarkable in large datasets of head impacts, the impacts causing injury are of high magnitude for the concussed individuals relative to their impact history. This finding suggests a need to account for differences in tolerance at the individual level. In this study, we identified control subjects for our concussed subjects who demonstrated traits we believed were correlated to factors thought to affect injury tolerance, including height, mass, age, race, and concussion history. A total of 502 college football players were instrumented with helmet-mounted accelerometer arrays and provided complete baseline assessment data, 44 of which sustained a total of 49 concussion. Biomechanical measures quantifying impact frequency and acceleration magnitude were compared between groups. On average, we found that concussed subjects experienced 93.8 more head impacts (p = 0.0031), 10.2 more high magnitude impacts (p = 0.0157), and 1.9 × greater risk-weighted exposure (p = 0.0175) than their physically matched controls. This finding provides further evidence that head impact data need to be considered at the individual level and that cohort wide assessments may be of little value in the context of concussion.
Acoustic Receptivity of a Boundary-Layer to Tollmien-Schlichting Waves Resulting From a Finite-Height Hump At Finite Reynolds-Numbers
Nayfeh, Ali H.; Ashour, O. N. (AIP Publishing, 1994-11-01)
The acoustic receptivity of a boundary layer to Tollmien-Schlichting (T-S) waves resulting from a finite-height hump at finite Reynolds numbers is investigated. The steady flow is calculated using an interacting boundary-layer (IBL) scheme that accounts for viscous/inviscid interactions. The unsteady flow is written as the sum of a Stokes wave and a traveling wave generated due to the interaction of the Stokes flow with the steady disturbance resulting from the hump. The traveling wave is governed by a set of nonhomogeneous equations, which is a generalization of the Orr-Sommerfeld equation. The solution of these nonhomogeneous equations is projected onto the quasiparallel eigenmode using the quasiparallel adjoint. This leads to a nonhomogeneous equation with variable coefficients governing the amplitude and phase of the T-S wave. Results are presented for the amplitude variation and the receptivity at finite Reynolds numbers. The results are in good agreement with the experimental results of Saric, Hoos, and Radeztsky [Boundary Layer Stability and Transition to Turbulence (ASME, New York, 1991), FED No. 114, pp. 17-22] for all tested hump heights at the two-tested sound pressure levels. Application of this paper's theory to small humps yields results that agree with those of Choudhari and Streett [Phys. Fluids A 4, 2495 (1992)]; and Crouch [Phys. Fluids A 4, 1408 (1992)]. Application of suction is shown to reduce the receptivity resulting from the hump.
Acoustic streaming in a waveguide with slowly varying height
Thompson, Charles (Acoustical Society of America, 1984-01-01)
An analysis of acoustic streaming in a two-dimensional waveguide having slowly varying height is presented. Special attention is paid to waveguides with cross sections that are small compared to the acoustic and/or wall wavelengths. It is shown that the dynamic behavior of the enclosed fluid can be parameterized by the values of three small parameters, ɛ, 1/S, and 1/R, where ɛ is the ratio of the typical duct height H₀ to the wall wavelength L₀, 1/S is the ratio of the typical oscillatory particle displacement U₀ to the typical duct height H₀ and 1/R is the ratio of the oscillatory boundary layer thickness lᵥ to the typical duct height H 0. An analytical solution describing the streaming flow in the duct is given in terms of a regular perturbation sequence in ɛ. It is shown that the oscillatory pressure must satisfy the lossy Webster horn equation to O(ɛ²) if the no slip boundary condition is to be satisfied. Outside the boundary layer it is shown that the time averaged slip velocity is the sum of two terms. The first term is proportional to the product of the incident and reflected wave amplitudes. The second term is proportional to the difference between the incident and reflected acoustic intensity of the wave. For small values of 1/S, 1/R, and ɛ the streaming solution given is shown to be valid until R/S 2 becomes of O(1).
Acoustic wave propagation in a circular cosh duct carrying a mean flow
Thompson, Charles; Sen, Rahul (Acoustical Society of America, 1987-09-01)
An analysis of acoustic wave propagation in a waveguide carrying an incompressible mean flow is presented. The radius of the waveguide is taken to vary slowly as a function of axial location. It is shown that the dynamic behavior of the enclosed fluid can be parametrized by the small parameter where is the ratio of the typical duct radius R 0 and the wall wavelength L 0. An analytical solution for the pressure field in the duct is given in terms of a regular perturbation expansion in The method of matched asymptotic expansions is used to evaluate the refractive effect of a thin mean-flow boundary layer on the acoustic pressure field. It is shown that in the case where the duct geometry conforms to that of a circular cosh duct the effect of higher-order turning points in the wave equation can be effectively handled by a closed-form solution that approximately solves the governing equations. The results of analysis are compared to those obtained using numerical methods. 1987 Acoustical Society of America
Acoustic waves in ducts with sinusoidally perturbed walls and mean flow
Nayfeh, Ali H. (Acoustical Society of America, 1975)
An analysis is presented of the propagation of acoustic waves in a hard-walled duct with sinusoidally perturbed walls and carrying mean flow. The results show that resonance occurs whenever the wavenumber of the wall undulations is approximately equal to the difference between the wavenumber of any two propagating modes. It is shown that neither of the resonating modes could exist in the duct without strongly exciting the other resonating mode.
Activation of bacterial channel MscL in mechanically stimulated droplet interface bilayers
Najem, Joseph S.; Dunlap, Myles D.; Rowe, Ian D.; Freeman, Eric C.; Grant, John Wallace; Sukharev, Sergei; Leo, Donald J. (Springer Nature, 2015-09-08)
MscL, a stretch-activated channel, saves bacteria experiencing hypo-osmotic shocks from lysis. Its high conductance and controllable activation makes it a strong candidate to serve as a transducer in stimuli-responsive biomolecular materials. Droplet interface bilayers (DIBs), flexible insulating scaffolds for such materials, can be used as a new platform for incorporation and activation of MscL. Here, we report the first reconstitution and activation of the low-threshold V23T mutant of MscL in a DIB as a response to axial compressions of the droplets. Gating occurs near maximum compression of both droplets where tension in the membrane is maximal. The observed 0.1-3 nS conductance levels correspond to the V23T-MscL sub-conductive and fully open states recorded in native bacterial membranes or liposomes. Geometrical analysis of droplets during compression indicates that both contact angle and total area of the water-oil interfaces contribute to the generation of tension in the bilayer. The measured expansion of the interfaces by 2.5% is predicted to generate a 4-6 mN/m tension in the bilayer, just sufficient for gating. This work clarifies the principles of interconversion between bulk and surface forces in the DIB, facilitates the measurements of fundamental membrane properties, and improves our understanding of MscL response to membrane tension.
Adaptive Control of the Atmospheric Plasma Spray Process for Functionally Graded Thermal Barrier Coatings
Guduri, Balachandar; Batra, Romesh C. (Hindawi, 2022-11-23)
Functionally graded coatings (FGCs) have a material composition continuously varying through the thickness but uniform in the surface parallel to the coated substrate. When used as a thermal barrier on a metallic substrate, the coating composition varies from an almost pure metal near the substrate to a pure ceramic adjacent to the outer surface exposed to a hot environment. Challenging issues in producing high quality FGCs in the presence of external disturbances with an atmospheric plasma spray process (APSP) include controlling the mean temperature, the mean axial velocity, and the positions of the constituent material particles when they arrive at the substrate to be coated. The unavoidable disturbances include fluctuations in the arc voltage and clogging of the powder in the delivery system. For a two-constituent coating, this work proposes using three modified robust model reference adaptive controllers based on the σ-modified laws and low frequency learning. One controller adjusts the current and flow rates of argon and hydrogen into the torch. The other two controllers adjust the distance of the two powder injector ports from the plasma jet axis and the average injection velocity of each powder. It is shown through numerical experiments that the three controllers implemented in an APSP consistently produce high-quality FGCs.
Adaptive process control for achieving consistent particles' states in atmospheric plasma spray process
Guduri, B.; Cybulsky, Michael; Pickrell, Gary R.; Batra, Romesh C. (2021-02-08)
The coatings produced by an atmospheric plasma spray process (APSP) must be of uniform quality. However, the complexity of the process and the random introduction of noise variables such as fluctuations in the powder injection rate and the arc voltage make it difficult to control the coating quality that has been shown to depend upon mean values of powder particles' temperature and speed, collectively called mean particles' states (MPSs), just before they impact the substrate. Here, we use a science-based methodology to develop a stable and adaptive controller for achieving consistent MPSs and thereby decrease the manufacturing cost. We first identify inputs into the APSP that significantly affect the MPSs and then formulate a relationship between these two quantities. When the MPSs deviate from their desired values, the adaptive controller is shown to successfully adjust the input parameters to correct them. The performance of the controller is tested via numerical experiments using the software, LAVA-P, that has been shown to well simulate the APSP.
Adding four-dimensional data assimilation by analysis nudging to the Model for Prediction Across Scales – Atmosphere
Bullock, Orren Russell, Jr.; Foroutan, Hosein; Gilliam, Robert C.; Herwehe, Jerold A. (Copernicus Publications, 2018-07-16)
The Model for Prediction Across Scales – Atmosphere (MPAS-A) has been modified to allow fourdimensional data assimilation (FDDA) by the nudging of temperature, humidity, and wind toward target values predefined on the MPAS-A computational mesh. The addition of nudging allows MPAS-A to be used as a global-scale meteorological driver for retrospective air quality modeling. The technique of “analysis nudging” developed for the Penn State/National Center for Atmospheric Research (NCAR) Mesoscale Model, and later applied in the Weather Research and Forecasting model, is implemented in MPAS-A with adaptations for its polygonal Voronoi mesh. Reference fields generated from 1° x 1° National Centers for Environmental Prediction (NCEP) FNL (Final) Operational Global Analysis data were used to constrain MPAS-A simulations on a 92–25 km variable-resolution mesh with refinement centered over the contiguous United States. Test simulations were conducted for January and July 2013 with and without FDDA, and compared to reference fields and near-surface meteorological observations. The results demonstrate that MPAS-A with analysis nudging has high fidelity to the reference data while still maintaining conservation of mass as in the unmodified model. The results also show that application of FDDA constrains model errors relative to 2m temperature, 2m water vapor mixing ratio, and 10m wind speed such that they continue to be at or below the magnitudes found at the start of each test period.
The adhesion function of the sodium channel beta subunit (beta 1) contributes to cardiac action potential propagation
Veeraraghavan, Rengasayee; Hoeker, Gregory S.; Alvarez-Laviada, Anita; Hoagland, Daniel T.; Wan, Xiaoping; King, D. Ryan; Sanchez-Alonso, Jose; Chen, Chunling; Jourdan, L. Jane; Isom, Lori L.; Deschenes, Isabelle; Smith, James W.; Gorelik, Julia; Poelzing, Steven; Gourdie, Robert G. (2018-08-14)
Computational modeling indicates that cardiac conduction may involve ephaptic coupling - intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized that beta 1(SCN1B) - mediated adhesion scaffolds trans-activating Na(V)1.5 (SCN5A) channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs), facilitating ephaptic coupling. Super-resolution imaging indicated preferential beta 1 localization at the perinexus, where it co-locates with Na(V)1.5. Smart patch clamp (SPC) indicated greater sodium current density (I-Na) at perinexi, relative to non-junctional sites. A novel, rationally designed peptide, beta adp1, potently and selectively inhibited beta 1-mediated adhesion, in electric cell-substrate impedance sensing studies. beta adp1 significantly widened perinexi in guinea pig ventricles, and selectively reduced perinexal I-Na, but not whole cell I-Na, in myocyte monolayers. In optical mapping studies, beta adp1 precipitated arrhythmogenic conduction slowing. In summary, beta 1-mediated adhesion at the perinexus facilitates action potential propagation between cardiomyocytes, and may represent a novel target for anti-arrhythmic therapies.
Adhesion Mechanics: Durability
Dillard, David A. (2022-12-21)
These slides contain figures prepared over my teaching career, and will appear in Chapter 20 of Advances in Structural Adhesive Bonding (2nd ed., 2023). The figures are provided for reuse under a CC BY-SA 4.0 license.
Adhesion Mechanics: Strength & Energy Metrics
Dillard, David A. (2023-01-21)
These slides contain figures prepared over my teaching career, and will appear in Chapter 14 of Advances in Structural Adhesive Bonding (2nd ed., 2023). The figures are provided for reuse under a CC BY-SA 4.0 license.
Adiabatic Following in Two-Photon Transition
Nayfeh, Munir H.; Nayfeh, Ali H. (American Physical Society, 1977-03-01)
The coherent interaction of two smoothly varying, near-resonant, two-photon pulses with a three-level system can be described by "two-photon damped Bloch equations" which are analogous to those for a one-photon transition in a two-level system except for the presence of a two-photon coupling and a frequency shift. These equations are solved for the cases γ1, γ2≪Ω, γ1=γ2, and γ2k2ε4Ω2, γ1≪Ω, where γ1 and γ2 are the atomic energy and phase relaxation widths, respectively, and Ω is the Rabi frequency. The leading contribution to the refractive index is intensity dependent, caused by the level shifts inherent in multiphoton processes; it includes a relaxation dependent part which is important at times shorter than γ−11. The second-order contributions depend on the square of the intensity and the time-integrated square of the intensity. The latter contribution, which is relaxation dependent, causes line asymmetry at the long-wavelength wing; it consists of a term proportional to γ2−γ1 and only important at early times and a term proportional to 2γ2−γ1.

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