Scholarly Works, Biomedical Engineering and Mechanics

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Research articles, presentations, and other scholarship

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Browsing Scholarly Works, Biomedical Engineering and Mechanics by Department "Electrical and Computer Engineering"

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    Closed 1st-Order And 2nd-Order Moment Equations For Stochastic Nonlinear Problems with Applications To Model Hydrodynamic And Vlasov-Plasma Turbulence
    Besieris, Ioannis M.; Stasiak, W. B. (AIP Publishing, 1976-09-01)
    Working along the lines of a procedure outlined by Keller, a technique is developed for deriving closed first_ and second_order moment equations for a general class of stochastic nonlinear equations by performing a renormalization at the level of the second moment. The work of Weinstock, as reformulated recently by Balescu and Misguich, is extended in order to obtain two equivalent representations for the second moment using an exact, nonperturbative, statistical approach. These general results, when specialized to the weak_coupling limit, lead to a complete set of closed equations for the first two moments within the framework of an approximation corresponding to Kraichnan's direct_interaction approximation. Additional restrictions result in a self_consistent set of equations for the first two moments in the stochastic quasilinear approximation. Finally, the technique is illustrated by considering its application to two specific physical problems: (1) modelhydrodynamicturbulence and (2) Vlasov_plasma turbulence in the presence of an external stochastic electric field.
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    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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    Development of a Multi-Pulse Conductivity Model for Liver Tissue Treated With Pulsed Electric Fields
    Zhao, Yajun; Zheng, Shuang; Beitel-White, Natalie; Liu, Hongmei; Yao, Chenguo; Davalos, Rafael V. (2020-05-19)
    Pulsed electric field treatment modalities typically utilize multiple pulses to permeabilize biological tissue. This electroporation process induces conductivity changes in the tissue, which are indicative of the extent of electroporation. In this study, we characterized the electroporation-induced conductivity changes using all treatment pulses instead of solely the first pulse as in conventional conductivity models. Rabbit liver tissue was employed to study the tissue conductivity changes caused by multiple, 100 mu s pulses delivered through flat plate electrodes. Voltage and current data were recorded during treatment and used to calculate the tissue conductivity during the entire pulsing process. Temperature data were also recorded to quantify the contribution of Joule heating to the conductivity according to the tissue temperature coefficient. By fitting all these data to a modified Heaviside function, where the two turning points (E-0, E-1) and the increase factor (A) are the main parameters, we calculated the conductivity as a function of the electric field (E), where the parameters of the Heaviside function (A and E-0) were functions of pulse number (N). With the resulting multi-factor conductivity model, a numerical electroporation simulation can predict the electrical current for multiple pulses more accurately than existing conductivity models. Moreover, the saturating behavior caused by electroporation can be explained by the saturation trends of the increase factor A in this model. The conductivity change induced by electroporation has a significant increase at about the first 30 pulses, then tends to saturate at 0.465 S/m. The proposed conductivity model can simulate the electroporation process more accurately than the conventional conductivity model. The electric field distribution computed using this model is essential for treatment planning in biomedical applications utilizing multiple pulsed electric fields, and the method proposed here, relating the pulse number to the conductivity through the variables in the Heaviside function, may be adapted to investigate the effect of other parameters, like pulse frequency and pulse width, on electroporation.
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    Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation
    Hendricks-Wenger, Alissa; Aycock, Kenneth N.; Nagai-Singer, Margaret A.; Coutermarsh-Ott, Sheryl; Lorenzo, Melvin F.; Gannon, Jessica; Uh, Kyungjun; Farrell, Kayla; Beitel-White, Natalie; Brock, Rebecca M.; Simon, Alexander; Morrison, Holly A.; Tuohy, Joanne L.; Clark-Deener, Sherrie; Vlaisavljevich, Eli; Davalos, Rafael V.; Lee, Kiho; Allen, Irving C. (Nature Research, 2021-04-07)
    New therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.
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    High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity
    Ringel-Scaia, Veronica M.; Beitel-White, Natalie; Lorenzo, Melvin F.; Brock, Rebecca M.; Huie, Kathleen E.; Coutermarsh-Ott, Sheryl; Eden, Kristin; McDaniel, Dylan K.; Verbridge, Scott S.; Rossmeisl, John H. Jr.; Oestreich, Kenneth J.; Davalos, Rafael V.; Allen, Irving C. (2019-06)
    Background: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques. Methods: Here, we utilized the mouse 4T1 mammary tumor model to evaluate H-FIRE treatment parameters on cancer progression and immune system activation in vitro and in vivo. Findings: H-FIRE effectively ablates the primary tumor and induces a pro-inflammatory shift in the tumor microenvironment. We further show that local treatment with H-FIRE significantly reduces 4T1 metastases. H-FIRE kills 4T1 cells through non-thermal mechanisms associated with necrosis and pyroptosis resulting in damage associated molecular pattern signaling in vitro and in vivo. Our data indicate that the level of tumor ablation correlates with increased activation of cellular immunity. Likewise, we show that the decrease in metastatic lesions is dependent on the intact immune system and H-FIRE generates 4T1 neoantigens that engage the adaptive immune system to significantly attenuate tumor progression. Interpretation: Cell death and tumor ablation following H-FIRE treatment activates the local innate immune system, which shifts the tumor microenvironment from an anti-inflammatory state to a pro-inflammatory state. The non-thermal damage to the cancer cells and increased innate immune system stimulation improves antigen presentation, resulting in the engagement of the adaptive immune system and improved systemic anti-tumor immunity. (C) 2019 The Authors. Published by Elsevier B.V.
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    iBLAST: Incremental BLAST of new sequences via automated e-value correction
    Dash, Sajal; Rahman, S. R.; Hines, H. M.; Feng, Wu-chun (PLoS, 2021-04-01)
    Search results from local alignment search tools use statistical scores that are sensitive to the size of the database to report the quality of the result. For example, NCBI BLAST reports the best matches using similarity scores and expect values (i.e., e-values) calculated against the database size. Given the astronomical growth in genomics data throughout a genomic research investigation, sequence databases grow as new sequences are continuously being added to these databases. As a consequence, the results (e.g., best hits) and associated statistics (e.g., e-values) for a specific set of queries may change over the course of a genomic investigation. Thus, to update the results of a previously conducted BLAST search to find the best matches on an updated database, scientists must currently rerun the BLAST search against the entire updated database, which translates into irrecoverable and, in turn, wasted execution time, money, and computational resources. To address this issue, we devise a novel and efficient method to redeem past BLAST searches by introducing iBLAST. iBLAST leverages previous BLAST search results to conduct the same query search but only on the incremental (i.e., newly added) part of the database, recomputes the associated critical statistics such as e-values, and combines these results to produce updated search results. Our experimental results and fidelity analyses show that iBLAST delivers search results that are identical to NCBI BLAST at a substantially reduced computational cost, i.e., iBLAST performs (1 + δ)/δ times faster than NCBI BLAST, where δ represents the fraction of database growth. We then present three different use cases to demonstrate that iBLAST can enable efficient biological discovery at a much faster speed with a substantially reduced computational cost.
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    A Kinetic Formulation Of 3-Dimensional Quantum Mechanical Harmonic-Oscillator Under A Random Perturbation
    Besieris, Ioannis M.; Stasiak, W. B.; Tappert, F. D. (AIP Publishing, 1978-02-01)
    The behavior of a three_dimensional, nonrelativistic, quantum mechanical harmonic oscillator is investigated under the influence of three distinct types of randomly fluctuating potential fields. Specifically, kinetic (or transport) equations are derived for the corresponding stochastic Wigner equation (the exact equation of evolution of the phase_space Wigner distribution density function) and the stochastic Liouville equation (correspondence limit approximation) using two closely related statistical techniques, the first_order smoothing and the long_time Markovian approximations. Several physically important averaged observables are calculated in special cases. In the absence of a deterministic inhomogeneous potential field (randomly perturbed, freely propagating particle), the results reduce to those reported previously by Besieris and Tappert.
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    Patient Derived Xenografts Expand Human Primary Pancreatic Tumor Tissue Availability for ex vivo Irreversible Electroporation Testing
    Brock, Rebecca M.; Beitel-White, Natalie; Coutermarsh-Ott, Sheryl; Grider, Douglas J.; Lorenzo, Melvin F.; Ringel-Scaia, Veronica M.; Manuchehrabadi, Navid; Martin, Robert C. G.; Davalos, Rafael V.; Allen, Irving C. (2020-05-22)
    New methods of tumor ablation have shown exciting efficacy in pre-clinical models but often demonstrate limited success in the clinic. Due to a lack of quality or quantity in primary malignant tissue specimens, therapeutic development and optimization studies are typically conducted on healthy tissue or cell-line derived rodent tumors that don't allow for high resolution modeling of mechanical, chemical, and biological properties. These surrogates do not accurately recapitulate many critical components of the tumor microenvironment that can impact in situ treatment success. Here, we propose utilizing patient-derived xenograft (PDX) models to propagate clinically relevant tumor specimens for the optimization and development of novel tumor ablation modalities. Specimens from three individual pancreatic ductal adenocarcinoma (PDAC) patients were utilized to generate PDX models. This process generated 15-18 tumors that were allowed to expand to 1.5 cm in diameter over the course of 50-70 days. The PDX tumors were morphologically and pathologically identical to primary tumor tissue. Likewise, the PDX tumors were also found to be physiologically superior to other in vitro and ex vivo models based on immortalized cell lines. We utilized the PDX tumors to refine and optimize irreversible electroporation (IRE) treatment parameters. IRE, a novel, non-thermal tumor ablation modality, is being evaluated in a diverse range of cancer clinical trials including pancreatic cancer. The PDX tumors were compared against either Pan02 mouse derived tumors or resected tissue from human PDAC patients. The PDX tumors demonstrated similar changes in electrical conductivity and Joule heating following IRE treatment. Computational modeling revealed a high similarity in the predicted ablation size of the PDX tumors that closely correlate with the data generated with the primary human pancreatic tumor tissue. Gene expression analysis revealed that IRE treatment resulted in an increase in biological pathway signaling associated with interferon gamma signaling, necrosis and mitochondria dysfunction, suggesting potential co-therapy targets. Together, these findings highlight the utility of the PDX system in tumor ablation modeling for IRE and increasing clinical application efficacy. It is also feasible that the use of PDX models will significantly benefit other ablation modality testing beyond IRE.
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    Starting a Fire Without Flame: The Induction of Cell Death and Inflammation in Electroporation-Based Tumor Ablation Strategies
    Brock, Rebecca M.; Beitel-White, Natalie; Davalos, Rafael V.; Allen, Irving C. (2020-07-28)
    New therapeutic strategies and paradigms are direly needed for the treatment of cancer. While the surgical removal of tumors is favored in most cancer treatment plans, resection options are often limited based on tumor localization. Over the last two decades, multiple tumor ablation strategies have emerged as promising stand-alone or combination therapeutic options for patients. These strategies are often employed to treat tumors in areas where surgical resection is not possible or where chemotherapeutics have proven ineffective. The type of cell death induced by the ablation modality is a critical aspect of therapeutic success that can impact the efficacy of the treatment and systemic anti-tumor immune system responses. Electroporation-based ablation technologies include electrochemotherapy, irreversible electroporation, and other modalities that rely on pulsed electric fields to create pores in cell membranes. These pores can either be reversible or irreversible depending on the electric field parameters and can induce cell death either alone or in combination with a therapeutic agent. However, there have been many controversial findings among these technologies as to the cell death type initiated, from apoptosis to pyroptosis. As cell death mechanisms can impact treatment side effects and efficacy, we review the main types of cell death induced by electroporation-based treatments and summarize the impact of these mechanisms on treatment response. We also discuss potential reasons behind the variability of findings such as the similarities between cell death pathways, differences between cell-types, and the variation in electric field strength across the treatment area.