Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the "damaged" network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times ([Formula: see text]) network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight.     

Finite Element Modeling Predictions of Region-specific Cell-matrix Mechanics in the Meniscus

The knee meniscus exhibits significant spatial variations in biochemical composition and cell morphology that reflect distinct phenotypes of cells located in the radial inner and outer regions. Associated with these cell phenotypes is a spatially heterogeneous microstructure and mechanical environment with the innermost regions experiencing higher fluid pressures and lower tensile strains than the outer regions. It is presently unknown, however, how meniscus tissue mechanics correlate with the local micromechanical environment of cells. In this study, theoretical models were developed to study mechanics of inner and outer meniscus cells with varying geometries. The results for an applied biaxial strain predict significant regional differences in the cellular mechanical environment with evidence of tensile strains along the collagen fiber direction of ~0.07 for the rounded inner cells, as compared to levels of 0.02–0.04 for the elongated outer meniscus cells. The results demonstrate an important mechanical role of extracellular matrix anisotropy and cell morphology in regulating the region-specific micromechanics of meniscus cells, that may further play a role in modulating cellular responses to mechanical stimuli.     

Finite Element Modeling of a Beetle Wing

Numerical simulation is a very important method for understanding the behaviors of insect flight. In this study, a method of building a finite element model is proposed on the basis of a real beetle wing, which is 50 mm long in the spanwise direction and 20 mm long in the chordwise direction. We scanned a real beetle wing using a scanner to get the 2D image. The scanned 2D image was used to produce CAD data of the outer lines of the membranes and veins. Then the lines were used to build the finite element model. The model was divided into 48 regions so that the variation in the thickness of the membranes and veins could be taken into account. The effect of the cross section of the veins on the exactness of the finite element model was investigated. The finite element model was used to simulate the bending test of a real beetle wing, and the analysis results are in agreement with the experimental results.     

The Mechanics of Anaphase B in a Basidiomycete as Revealed by Laser Microbeam Microsurgery

Bayles, C. J., Aist, J. R., and Berns, M. W. 1993. The mechanics of anaphase B in a basidiomycete as revealed by laser microbeam microsurgery. Experimental Mycology 17, 191-199. Cytoplasmic forces were found to be actively pulling on the spindle pole bodies during anaphase B in the dikaryotic, basidiomycete fungus, Helicobasidium mompa. When the spindle of one nucleus was severed with a laser microbeam at mid anaphase B, its two spindle pole bodies separated at a much faster rate than did those of the intact spindle in the other nucleus of the same cell. Since astral microtubule populations apparently reach their maximum during anaphase B in this fungus, we suggest that these microtubules may be involved in the cytoplasmic pulling forces. The spindle appears to act primarily as a governor, regulating the rate at which the spindle pole bodies are separated.     

Adaptive Finite Element Analysis of the Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics

The nonlinear partial differential equations of the anisotropic biphasic theory of tissue-equivalent mechanics are solved with axial symmetry by an adaptive finite element system. The adaptive procedure operates within a method-of-lines framework using finite elements in space and backward difference software in time. Spatial meshes are automatically refined, coarsened, and relocated in response to error indications and material deformation. Problems with arbitrarily complex two-dimensional regions may be addressed. With meshes graded in high-error regions, the adaptive solutions have fewer degrees of freedom than solutions with comparable accuracy obtained on fixed quasi-uniform meshes. The adaptive software is used to address problems involving an isometric cell traction assay, where a cylindrical tissue equivalent is adhered at its end to fixed circular platens; a prototypical bioartificial artery; and a novel configuration that is intended as an initial step in a study to determine bioartificial arteries having optimal collagen and cell concentrations.     

Finite Element Analysis of the Contact Mechanics of Ceramic-on-Ceramic Hip Resurfacing Prostheses

<正> Ceramics are good alternative to metal as bearing couple materials because of their better wear resistance. A Finite Element(FE) study was performed to investigate the contact mechanics and stress distribution of Ceramic-on-Ceramic (COC) hip resurfacingprostheses. It was focused in particular on a parametric study to examine the effects of radial clearance, loading,alumina coating on the implants, bone quality, and fixation of cup-bone interface. It was found that a reduction in the radialclearance had the most significant effect on the predicted contact pressure distribution among all of the parameters considered inthis study. It was determined that there was a significant influence of non-metallic materials, such as the bone underneath thebearing components, on the predicted contact mechanics. Stress shielding within the bone tissue was found to be a major concernwhen regarding the use of ceramic as an alternative to metallic resurfacing prostheses. Therefore, using alumina implantswith a metal backing was found to be the best design for ceramic resurfacing prostheses in this study. The loading, bone quality,and acetabular cup fixation conditions were found to have only minor effects on the predicted contact pressure distribution alongthe bearing surfaces.     

Adaptive Finite Element Analysis of the Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics

Abstract

The nonlinear partial differential equations of the anisotropic biphasic theory of tissue-equivalent mechanics are solved with axial symmetry by an adaptive finite element system. The adaptive procedure operates within a method-of-lines framework using finite elements in space and backward difference software in time. Spatial meshes are automatically refined, coarsened, and relocated in response to error indications and material deformation. Problems with arbitrarily complex two-dimensional regions may be addressed. With meshes graded in high-error regions, the adaptive solutions have fewer degrees of freedom than solutions with comparable accuracy obtained on fixed quasi-uniform meshes. The adaptive software is used to address problems involving an isometric cell traction assay, where a cylindrical tissue equivalent is adhered at its end to fixed circular platens; a prototypical bioartificial artery; and a novel configuration that is intended as an initial step in a study to determine bioartificial arteries having optimal collagen and cell concentrations.     

Permeability of Gemcitabine and PBPK Modeling to Assess Oral Administration

Gemcitabine is a nucleoside analog effective against several solid tumors. Standard treatment consists of an intravenous infusion over 30 min. This is an invasive, uncomfortable and often painful method, involving recurring visits to the hospital and costs associated with medical staff and equipment. Gemcitabine’s activity is significantly limited by numerous factors, including metabolic inactivation, rapid systemic clearance of gemcitabine and transporter deficiency-associated resistance. As such, there have been research efforts to improve gemcitabine-based therapy efficacy, as well as strategies to enhance its oral bioavailability. In this work, gemcitabine in vitro and clinical data were analyzed and in silico tools were used to study the pharmacokinetics of gemcitabine after oral administration following different regimens. Several physiologically based pharmacokinetic (PBPK) models were developed using simulation software GastroPlus™, predicting the PK parameters and plasma concentration–time profiles. The integrative biomedical data analyses presented here are promising, with some regimens of oral administration reaching higher AUC in comparison to the traditional IV infusion, supporting this route of administration as a viable alternative to IV infusions. This study further contributes to personalized health care based on potential new formulations for oral administration of gemcitabine, as well nanotechnology-based drug delivery systems.     

Data-Driven Modeling to Assess Receptivity for Rift Valley Fever Virus

Rift Valley Fever virus (RVFV) is an enzootic virus that causes extensive morbidity and mortality in domestic ruminants in Africa, and it has shown the potential to invade other areas such as the Arabian Peninsula. Here, we develop methods for linking mathematical models to real-world data that could be used for continent-scale risk assessment given adequate data on local host and vector populations. We have applied the methods to a well-studied agricultural region of California with 1 million dairy cattle, abundant and competent mosquito vectors, and a permissive climate that has enabled consistent transmission of West Nile virus and historically other arboviruses. Our results suggest that RVFV outbreaks could occur from February–November, but would progress slowly during winter–early spring or early fall and be limited spatially to areas with early increases in vector abundance. Risk was greatest in summer, when the areas at risk broadened to include most of the dairy farms in the study region, indicating the potential for considerable economic losses if an introduction were to occur. To assess the threat that RVFV poses to North America, including what-if scenarios for introduction and control strategies, models such as this one should be an integral part of the process; however, modeling must be paralleled by efforts to address the numerous remaining gaps in data and knowledge for this system.     

结合薄层CT技术建立下颌第一前磨牙三维有限元模型

目的结合薄层CT技术建立下颌第一前磨牙三维有限元模型。方法对正常人下颌第一前磨牙进行薄层CT扫描及图像处理,通过Matlab和ANSYS软件建立三维有限元模型,并加载验证模型力学分析的可行性。结果建立了包含髓腔的下颌第一前磨牙的三维有限元模型,得到101564个单元,144053个节点。载荷后的应力分布主要集中在颊尖部位和根尖部位,牙颈部受力较小。结论薄层CT技术与Matlab和ANSYS软件相结合,建立包含髓腔的下颌第一前磨牙的三维有限元模型,精度高、速度快,使用灵活,为后期的楔缺模型建立和分析奠定了基础。     

Static and Dynamic Mechanics Analysis on Artificial Hip Joints with Different Interface Designs by the Finite Element Method

Four different structural models of artificial joints were developed and the finite element method （FEM） was employed to investigate their mechanical characteristics under static and dynamic conditions. The materials used in the FEM calculation were ultra-high molecular weight polyethylene （UHMWPE）, 316L stainless steel, CoCrMo alloy and Ti6A14V alloy. The stress distribution, strain, and elastic deformation under static and dynamic conditions were obtained. Analysis and comparison of the ~alculation results of different models were conducted. It is shown that with the same parameters the model of a metallic femur head covered with an artificial cartilage layer is more similar to the structure of the natural human joint and its mechanical characteristics are the best of the four models.     

LISS钢板治疗股骨远端骨折有限元建模及分析

目的建立LISS-DF治疗股骨远端骨折近端螺钉不同单双皮质固定的三维有限元模型,并进行初步生物力学分析。方法提取CT图片相关数据,利用自行编写程序生成命令流文件,建立完整股骨以及16个不同LISS-DF治疗股骨远端AO分型33-A3型骨折的实体模型（钢板和股骨不接触、螺钉分别固定于钢板和股骨）,进行网格划分。分析不同载荷作用下完整股骨和LISS钢板近端螺钉全双皮质固定治疗骨折的模型受力状况。结果建立了相关的有限元模型。不同载荷作用下,LISS钢板近端螺钉全双皮质固定模型和完整股骨的应力集中均位于股骨颈内侧和股骨干外侧中下1/3处。相同载荷作用下,LISS钢板近端螺钉全双皮质固定模型的股骨颈部最大等效应力值略减小,股骨干最大等效应力值明显减小。结论研究建立的三维有限元模型,为应用LISS治疗股骨骨折的生物力学分析提供了良好的实验平台和基础。从生物力学角度而言,LISS-DF近端螺钉全双皮质固定为治疗股骨远端复杂骨折的有效方法。     

Laser Ablation of the Zebrafish Pronephros to Study Renal Epithelial Regeneration

Acute kidney injury (AKI) is characterized by high mortality rates from deterioration of renal function over a period of hours or days that culminates in renal failure¹. AKI can be caused by a number of factors including ischemia, drug-based toxicity, or obstructive injury¹. This results in an inability to maintain fluid and electrolyte homeostasis. While AKI has been observed for decades, effective clinical therapies have yet to be developed. Intriguingly, some patients with AKI recover renal functions over time, a mysterious phenomenon that has been only rudimentally characterized^1,2. Research using mammalian models of AKI has shown that ischemic or nephrotoxin-injured kidneys experience epithelial cell death in nephron tubules^1,2, the functional units of the kidney that are made up of a series of specialized regions (segments) of epithelial cell types³. Within nephrons, epithelial cell death is highest in proximal tubule cells. There is evidence that suggests cell destruction is followed by dedifferentiation, proliferation, and migration of surrounding epithelial cells, which can regenerate the nephron entirely^1,2. However, there are many unanswered questions about the mechanisms of renal epithelial regeneration, ranging from the signals that modulate these events to reasons for the wide variation of abilities among humans to regenerate injured kidneys.The larval zebrafish provides an excellent model to study kidney epithelial regeneration as its pronephric kidney is comprised of nephrons that are conserved with higher vertebrates including mammals^4,5. The nephrons of zebrafish larvae can be visualized with fluorescence techniques because of the relative transparency of the young zebrafish⁶. This provides a unique opportunity to image cell and molecular changes in real-time, in contrast to mammalian models where nephrons are inaccessible because the kidneys are structurally complex systems internalized within the animal. Recent studies have employed the aminoglycoside gentamicin as a toxic causative agent for study of AKI and subsequent renal failure: gentamicin and other antibiotics have been shown to cause AKI in humans, and researchers have formulated methods to use this agent to trigger kidney damage in zebrafish^7,8. However, the effects of aminoglycoside toxicity in zebrafish larvae are catastrophic and lethal, which presents a difficulty when studying epithelial regeneration and function over time. Our method presents the use of targeted cell ablation as a novel tool for the study of epithelial injury in zebrafish. Laser ablation gives researchers the ability to induce cell death in a limited population of cells. Varying areas of cells can be targeted based on morphological location, function, or even expression of a particular cellular phenotype. Thus, laser ablation will increase the specificity of what researchers can study, and can be a powerful new approach to shed light on the mechanisms of renal epithelial regeneration. This protocol can be broadly applied to target cell populations in other organs in the zebrafish embryo to study injury and regeneration in any number of contexts of interest.     

Linking Changes in Epithelial Morphogenesis to Cancer Mutations Using Computational Modeling

Most tumors arise from epithelial tissues, such as mammary glands and lobules, and their initiation is associated with the disruption of a finely defined epithelial architecture. Progression from intraductal to invasive tumors is related to genetic mutations that occur at a subcellular level but manifest themselves as functional and morphological changes at the cellular and tissue scales, respectively. Elevated proliferation and loss of epithelial polarization are the two most noticeable changes in cell phenotypes during this process. As a result, many three-dimensional cultures of tumorigenic clones show highly aberrant morphologies when compared to regular epithelial monolayers enclosing the hollow lumen (acini). In order to shed light on phenotypic changes associated with tumor cells, we applied the bio-mechanical IBCell model of normal epithelial morphogenesis quantitatively matched to data acquired from the non-tumorigenic human mammary cell line, MCF10A. We then used a high-throughput simulation study to reveal how modifications in model parameters influence changes in the simulated architecture. Three parameters have been considered in our study, which define cell sensitivity to proliferative, apoptotic and cell-ECM adhesive cues. By mapping experimental morphologies of four MCF10A-derived cell lines carrying different oncogenic mutations onto the model parameter space, we identified changes in cellular processes potentially underlying structural modifications of these mutants. As a case study, we focused on MCF10A cells expressing an oncogenic mutant HER2-YVMA to quantitatively assess changes in cell doubling time, cell apoptotic rate, and cell sensitivity to ECM accumulation when compared to the parental non-tumorigenic cell line. By mapping in vitro mutant morphologies onto in silico ones we have generated a means of linking the morphological and molecular scales via computational modeling. Thus, IBCell in combination with 3D acini cultures can form a computational/experimental platform for suggesting the relationship between the histopathology of neoplastic lesions and their underlying molecular defects.     

Applications of Finite Element Analyses to Problems in Plant Morphology

Methods of describing the geometry and position of cells bymeans of the finite method are applied to selected extant (Fucus,Cutleria, and Calypogeia) and fossil plant genera (Protosaloinia,Spongiophyton, and Parka). The gross morphology and some aspectsof the ontogeny of these six genera are simulated by means ofcomputer; the pseudo- and parenchymatous tissue organizationsare mathematically characterized. Simulated representationsof living (Fucus and Cutleria) and fossil algae (Protosalcinia,Spongio phyton, and Parka) are shown to be distinctively differentfrom those of the bryophytes. The application of the finiteelement method to problems of plant morphology makes possiblethe dynamic simulations of some aspects of growth and developmentin living plants, and the extrapolation of missing stages inthe ontogeny of fossil plants.