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.     

三种固定液对两种氧化应激细胞模型Bclin1和LC3蛋白免疫荧光染色的影响

摘要 目的：比较采用三种不同的固定液对两种氧化应激细胞模型Beclin1和LC3蛋白免疫荧光染色的影响。方法：本研究使用丙酮/甲醇（1:1）固定液、甲醇固定液和4%多聚甲醛三种固定液分别对氧化应激细胞模型大鼠原代心肌成纤维细胞和MCF-7乳腺癌细胞株进行固定,然后再分别进行免疫荧光双染实验,对比三种固定液固定后对自噬关键调控蛋白Beclin1和LC3染色效果。结果：三种固定液对氧化应激细胞模型Beclin1和LC3蛋白免疫荧光染色结果存在较大差异。丙酮/甲醇（1:1）固定液固定后免疫荧光染色效果最佳,细胞结构清晰可见,两种蛋白定位表达清晰,甲醇固定液次之,4%多聚甲醛固定液效果欠佳。结论：在对大鼠原代心肌成纤维细胞和MCF-7乳腺癌细胞进行自噬相关蛋白免疫荧光双染色实验中,在使用其它固定液染色效果不佳的情况下,可以选择应用丙酮/甲醇（1:1）固定液固定,再进行免疫荧光染色;根据不同实验需求相应选择更适宜的固定液,以达到最佳的荧光染色结果。     

Absorbing phenomena and escaping time for Muller's ratchet in adaptive landscape

Background

The accumulation of deleterious mutations of a population directly contributes to the fate as to how long the population would exist, a process often described as Muller's ratchet with the absorbing phenomenon. The key to understand this absorbing phenomenon is to characterize the decaying time of the fittest class of the population. Adaptive landscape introduced by Wright, a re-emerging powerful concept in systems biology, is used as a tool to describe biological processes. To our knowledge, the dynamical behaviors for Muller's ratchet over the full parameter regimes are not studied from the point of the adaptive landscape. And the characterization of the absorbing phenomenon is not yet quantitatively obtained without extraneous assumptions as well.

Methods

We describe how Muller's ratchet can be mapped to the classical Wright-Fisher process in both discrete and continuous manners. Furthermore, we construct the adaptive landscape for the system analytically from the general diffusion equation. The constructed adaptive landscape is independent of the existence and normalization of the stationary distribution. We derive the formula of the single click time in finite and infinite potential barrier for all parameters regimes by mean first passage time.

Results

We describe the dynamical behavior of the population exposed to Muller's ratchet in all parameters regimes by adaptive landscape. The adaptive landscape has rich structures such as finite and infinite potential, real and imaginary fixed points. We give the formula about the single click time with finite and infinite potential. And we find the single click time increases with selection rates and population size increasing, decreases with mutation rates increasing. These results provide a new understanding of infinite potential. We analytically demonstrate the adaptive and unadaptive states for the whole parameters regimes. Interesting issues about the parameters regions with the imaginary fixed points is demonstrated. Most importantly, we find that the absorbing phenomenon is characterized by the adaptive landscape and the single click time without any extraneous assumptions. These results suggest a graphical and quantitative framework to study the absorbing phenomenon.

     

肱骨有限元模型建立及生物力学分析

目的:以成人肱骨为例,将医学图像三维重建技术和有限元方法结合应用于正骨手法研究,建立正常肱骨有限元模型,验证模型的有效性并进行生物力学分析。方法:选择一位青年男性志愿者,对其上肢自尺桡骨上端至肱骨头进行连续断层扫描,得到CT图像,将CT数据导入MIMICS软件中,通过图像分割、三维重建和材料属性赋值,构建正常肱骨有限元模型,利用ANSYS软件进行力学分析,与文献中肱骨的生物力学数据相比较,以此验证模型的有效性。结果:建立了正常肱骨三维几何模型和有限元模型。利用ANSYS软件,对模型进行了有效性验证。所建模型物理特性与真实骨骼相近,能很好地反映骨骼的力学变化,实现手法的定量分析。结论:所建立的肱骨模型外形逼真、在不同载荷下的应力值与相关文献一致,可用作中医仿真系统中的虚拟骨折模型。     

Anisotropic adaptive finite element method for modelling blood flow

In this study, we present an adaptive anisotropic finite element method (FEM) and demonstrate how computational efficiency can be increased when applying the method to the simulation of blood flow in the cardiovascular system. We use the SUPG formulation for the transient 3D incompressible Navier–Stokes equations which are discretised by linear finite elements for both the pressure and the velocity field.

Given the pulsatile nature of the flow in blood vessels we have pursued adaptivity based on the average flow over a cardiac cycle. Error indicators are derived to define an anisotropic mesh metric field. Mesh modification algorithms are used to anisotropically adapt the mesh according to the desired size field. We demonstrate the efficiency of the method by first applying it to pulsatile flow in a straight cylindrical vessel and then to a porcine aorta with a stenosis bypassed by a graft. We demonstrate that the use of an anisotropic adaptive FEM can result in an order of magnitude reduction in computing time with no loss of accuracy compared to analyses obtained with uniform meshes.     

A dosimetric evaluation of IGART strategies for cervix cancer treatment

PurposeImage guided adaptive radiotherapy (IGART) strategies can be used to include the temporal aspects of radiotherapy treatment. A dosimetric evaluation of on- and off-line adaptive strategies are done in this study.MethodsA library of equivalent uniform dose (EUD)-based Intensity Modulated Radiotherapy Treatment plans with incrementally increasing clinical target volume (CTV)-to-planning target volume (PTV) margins were developed for 10 patients. Utilizing daily computed tomography (CT) images an on-line strategy using a margin-of-the-day (MOD) concept that selects the best plan from the library was employed. This was compared to an off-line strategy with full analysis of accumulated dose between fractions where dosimetric deviations from the treatment intent triggered plan adaptation. A fixed margin treatment approach was used as benchmark.ResultsUsing fixed margins of <15 mm lead to under-dosages of more than 5 Gy in total delivered dose. The average CTV EUD for the off-line and on-line strategy was 50.0 ± 5.0 Gy and 50.4 ± 2.0 Gy respectively and OAR doses were comparable.ConclusionA fixed margin treatment approach yields a significant probability of CTV under-dosage. Using EUD dose metrics CTV coverage can be restored in both the off-line and on-line adaptive strategies at acceptable OAR dose levels. Considering the workload and time on the treatment machine, the off-line strategy proves to be sufficient and more practical.     

A new strategy for craniospinal axis localization and adaptive dosimetric evaluation using cone beam CT

Background and AimComputational complexities encountered in craniospinal irradiation (CSI) have been widely investigated with different planning strategies. However, localization of the entire craniospinal axis (CSA) and evaluation of adaptive treatment plans have traditionally been ignored in CSI treatment. In this study, a new strategy for CSI with comprehensive CSA localization and adaptive plan evaluation has been demonstrated using cone beam CT with extended longitudinal field-of-view (CBCT_eLFOV).Materials and MethodsMulti-scan CBCT images were acquired with fixed longitudinal table translations (with 1 cm cone-beam overlap) and then fused into a single DICOM-set using the custom software coded in MatLab™. A novel approach for validation of CBCT_eLFOV was demonstrated by combined geometry of Catphan-504 and Catphan-604 phantoms. To simulate actual treatment scenarios, at first, the end-to-end workflow of CSI with VMAT was investigated using an anthropomorphic phantom and then applied for two patients (based on random selection).ResultsThe fused CBCT_eLFOV images were in excellent agreement with planning CT (pCT). The custom developed software effectively manages spatial misalignments arising out of the uncertainties in treatment/setup geometry. Although the structures mapped from pCT to CBCT_eLFOV showed minimal variations, a maximum spatial displacement of up to 1.2 cm (and the mean of 0.8 ± 0.3 cm) was recorded in phantom study. Adaptive plan evaluation of patient paradigms showed the likelihood of under-dosing the craniospinal target.ConclusionOur protocol serves as a guide for precise localization of entire CSA and to ensure adequate dose to the large and complex targets. It can also be adapted for other complex treatment techniques such as total-marrow-irradiation and total-lymphoid-irradiation.     

Adaptive Mutation in Saccharomyces cerevisiae

ABSTRACT

Adaptive mutation is a generic term for processes that allow individual cells of nonproliferating cell populations to acquire advantageous mutations and thereby to overcome the strong selective pressure of proliferation-limiting environmental conditions. Prerequisites for an occurrence of adaptive mutation are that the selective conditions are nonlethal and that a restart of proliferation may be accomplished by some genetic change in principle. The importance of adaptive mutation is derived from the assumption that it may, on the one hand, result in an accelerated evolution of microorganisms and, on the other, in multicellular organisms may contribute to a breakout of somatic cells from negative growth regulation, i.e., to cancerogenesis. Most information on adaptive mutation in eukaryotes has been gained with the budding yeast Saccharomyces cerevisiae. This review focuses comprehensively on adaptive mutation in this organism and summarizes our current understanding of this issue.     

A dynamical model for plant cell wall architecture formation

We discuss a dynamical mathematical model to explain cell wall architecture in plant cells. The highly regular textures observed in cell walls reflect the spatial organisation of the cellulose microfibrils (CMFs), the most important structural component of cell walls. Based on a geometrical theory proposed earlier [A. M. C. Emons, Plant, Cell and Environment 17, 3–14 (1994)], the present model describes the space-time evolution of the density of the so-called rosettes, the CMF synthesizing complexes. The motion of these rosettes in the plasma membrane is assumed to be governed by an optimal packing constraint on the CMFs plus adherent matrix material, that couples the direction of motion, and hence the orientation of the CMF being deposited, to the local density of rosettes. The rosettes are created inside the cell in the endoplasmatic reticulum and reach the cell-membrane via vesicles derived from Golgi-bodies. After being inserted into the plasma membrane they are assumed to be operative for a fixed, finite lifetime. The plasma membrane domains within which rosettes are activated are themselves also supposed to be mobile. We propose a feedback mechanism that precludes the density of rosettes to rise beyond a maximum dictated by the geometry of the cell. The above ingredients lead to a quasi-linear first order PDE for the rosette-density. Using the method of characteristics this equation can be cast into a set of first order ODEs, one of which is retarded. We discuss the analytic solutions of the model that give rise to helicoidal, crossed polylamellate, helical, axial and random textures, since all cell walls are composed of (or combinations of) these textures. Received: 10 July 1999 / Revised version: 7 June 2000 / Published online: 16 February 2001     

ImageParser: a tool for finite element generation from three-dimensional medical images

Background

The finite element method (FEM) is a powerful mathematical tool to simulate and visualize the mechanical deformation of tissues and organs during medical examinations or interventions. It is yet a challenge to build up an FEM mesh directly from a volumetric image partially because the regions (or structures) of interest (ROIs) may be irregular and fuzzy.

Methods

A software package, ImageParser, is developed to generate an FEM mesh from 3-D tomographic medical images. This software uses a semi-automatic method to detect ROIs from the context of image including neighboring tissues and organs, completes segmentation of different tissues, and meshes the organ into elements.

Results

The ImageParser is shown to build up an FEM model for simulating the mechanical responses of the breast based on 3-D CT images. The breast is compressed by two plate paddles under an overall displacement as large as 20% of the initial distance between the paddles. The strain and tangential Young's modulus distributions are specified for the biomechanical analysis of breast tissues.

Conclusion

The ImageParser can successfully exact the geometry of ROIs from a complex medical image and generate the FEM mesh with customer-defined segmentation information.

     

Impact of a Moving Noise Masker on Speech Perception in Cochlear Implant Users

ObjectivesPrevious studies investigating speech perception in noise have typically been conducted with static masker positions. The aim of this study was to investigate the effect of spatial separation of source and masker (spatial release from masking, SRM) in a moving masker setup and to evaluate the impact of adaptive beamforming in comparison with fixed directional microphones in cochlear implant (CI) users.DesignSpeech reception thresholds (SRT) were measured in S₀N₀ and in a moving masker setup (S₀N_move) in 12 normal hearing participants and 14 CI users (7 subjects bilateral, 7 bimodal with a hearing aid in the contralateral ear). Speech processor settings were a moderately directional microphone, a fixed beamformer, or an adaptive beamformer. The moving noise source was generated by means of wave field synthesis and was smoothly moved in a shape of a half-circle from one ear to the contralateral ear. Noise was presented in either of two conditions: continuous or modulated.ResultsSRTs in the S₀N_move setup were significantly improved compared to the S₀N₀ setup for both the normal hearing control group and the bilateral group in continuous noise, and for the control group in modulated noise. There was no effect of subject group. A significant effect of directional sensitivity was found in the S₀N_move setup. In the bilateral group, the adaptive beamformer achieved lower SRTs than the fixed beamformer setting. Adaptive beamforming improved SRT in both CI user groups substantially by about 3 dB (bimodal group) and 8 dB (bilateral group) depending on masker type.ConclusionsCI users showed SRM that was comparable to normal hearing subjects. In listening situations of everyday life with spatial separation of source and masker, directional microphones significantly improved speech perception with individual improvements of up to 15 dB SNR. Users of bilateral speech processors with both directional microphones obtained the highest benefit.     

The construction of the scoliosis 3D finite element model and the biomechanical analysis of PVCR orthopaedy

ObjectiveThe objective is to investigate the biomechanical conditions of the Posterior Vertebral Column Resection (PVCR) of the constructed scoliosis 3D finite element model.MethodsA patient with scoliosis was selected; before the PVCR orthopaedy, the patient was submitted to the radiography of normal and lateral full-length vertebral column scans and the total magnetic resonance imaging (MRI) scans; then, the idiopathic scoliosis model was constructed by the 3D finite element method, and the 3D finite element software utilized in the process of model construction included Mimics software, Geomagic Studio 12 software, and Unigraphic 8.0 (UG 8.0) software; in addition, PVCR orthopaedy was utilized to correct the scoliosis of the patient, and the biomechanical parameters, such as orthodontic force, vertebral body displacement, orthopedic rod stress, stress on the pin-bone interface of the vertebral body surface, and the stress on the intervertebral disc, were studied.ResultsThe 3D effective finite element model of scoliosis was successfully constructed by the Mimics software, the Geomagic Studio 12 software, and the UG 8.0 software, and the effectiveness was tested. PVCR orthopaedy could effectively solve the problem of scoliosis. The magnitude of the orthodontic force that a patient needed depended on the physical conditions and the personal orthodontic requirements of the patient. The maximum vertebral body displacement on the X-axis was the vertebral body L1, the maximum displacement on the Y-axis was the vertebral body T3, the maximum displacement on the Z-axis was the vertebral body T1, and the rang of orthopedic rod stress was 0.0050214e⁷ MPa to 0.045217e⁷ MPa, in which the maximum stress of 2 vertebral bodies in, above, and below the osteotomy area reached 0.045217e⁷ MPa, the stress on the pin-bone interface of the T10 vertebral body surface reached 11.83 MPa, and the stress of T8/T9 intervertebral disc reached 13.84 MPa.ConclusionThe 3D finite element model based on 3D finite element software was highly efficient, and its numerical simulation was accurate, which was important for the subsequent biomechanical analysis of PVCR orthopaedy. In addition, the vertebral stress of PVCR orthopaedy was different in each body part, which was mainly affected by the applied orthodontic force and the sites of the orthodontic area.     

Evaluation of the Adaptive Umbrella Sampling Method

Abstract

The adaptive umbrella sampling technique, introduced recently to improve the probability ratio method and found to perform more reliably than the customary harmonic umbrella sampling, is tested and compared with other free energy methods. One of the tests applies the method to a transition involving a chemical change: calculation of the hydration free energy difference between acetone and dimethylamine and the other test calculates the conformational free energy difference between the C ₇ and α_R conformations of the alanide dipeptide. The dipeptide problem is also treated by two types of thermodynamic integrations and by the perturbation method. The result for the acetone-dimethylamine problem is compared with previous calculations on the same system using the perturbation method, overlap ratio method and finite difference thermodynamic integration. Enhancements to the adaptive umbrella sampling method are also presented.     

Ultrasound-facilitated formalin fixation of biological specimens

Abstract

In a previous study, we showed that ultrasound can dramatically reduce the time required for tissue fixation in formalin. It generally is believed that ultrasound increases the speed of tissue fixation in two possible ways: 1) increasing the speed of penetration of fixative molecules into tissue samples and 2) increasing the speed of cross-linking reactions. We addressed here the second possible way by using protein solutions and cultured cells, which minimized the effects of the penetration factor. Proteins or cultured cells in solution were fixed with formalin with or without ultrasound irradiation. Fixed proteins and cell lysates then were separated by SDS-poly acrylamide gel electrophoresis and subjected to Western blotting to examine cross-linking formation in certain proteins. Unexpectedly, irradiation with ultrasound did not produce an observable difference in the rate of cross-linking in protein solutions. In similar experiments using cultured cells, however, we observed a significant reduction in recovery of certain proteins from cells fixed by formalin under the influence of ultrasound, which indicated that the ultrasound fixation procedure accelerated cross-linking formation within cells. Studies on protein and cell fixation without ultrasound showed that cross-linking formation was closely related to incubation temperature, which indicates that the heating function, which is inherently associated with ultrasound is another major factor in the ability of ultrasound to accelerate cross-linking.     

Renal adaptive response to exposure to low doses of uranyl nitrate and sodium fluoride in mice

BackgroundDespite their differences in physicochemical properties, both uranium (U) and fluoride (F) are nephrotoxicants at high doses but their adverse effects at low doses are still the subject of debate. METHODS: This study aims to improve the knowledge of the biological mechanisms involved through an adaptive response model of C57BL/6 J mice chronically exposed to low priming doses of U (0, 10, 20 and 40 mg/L) or F (0, 15, 30 and 50 mg/L) and then challenged with acute exposure of 5 mg/kg U or 7.5 mg/kg NaF.ResultsWe showed that an adaptive response occurred with priming exposures to 20 mg/L U and 50 mg/L F, with decreased levels of the biomarkers KIM-1 and CLU compared to those in animals that received the challenge dose only (positive control). The adaptive mechanisms involved a decrease in caspase 3/7 activities in animals exposed to 20 mg/L U and a decrease in in situ VCAM expression in mice exposed to 50 mg/L F. However, autophagy and the UPR were induced independently of priming exposure to U or F and could not be identified as adaptive mechanisms to U or F.ConclusionTaken together, these results allow us to identify renal adaptive responses to U and F at doses of 20 and 50 mg/L, probably through decrease apoptosis and inflammatory cell recruitment.     

On the Use of Infinite Elements for the Determination of Optimal Closure Patterns based on Stress Analysis

Solid infinite elements are used in conjunction with finite elements to compute the stress and displacement distribution resulting from the suturing of wounds of symmetric and nonsymmetric shapes in orthotropic, abdominal human skin. The optimal pattern of suturing of wounds are investigated from a stress perspective. Highly accurate, quantitative and qualitative improvements over the use of finite elements to approximate distant boundaries are obtained. Numerical results quantitatively agree with analytic results computed using complex analysis techniques. The technique used and the results obtained will aid surgeons in closing nonsymmetrical wounds on regions of the body that exhibit orthotropy.     

Ultrastructure of testes and spermatogenesis in the trombiculid mite,Hirsutiella zachvatkini (Schluger)

Summary

Spermatogenesis and sperm ultrastructure of the trombiculid mite Hirsutiella zachvatkini (Schluger 1948) have been investigated using transmission electron microscopy and compared with other arachnids studied. Sperm differentiation takes place in groups of synchronously developed germ cells of the two large sac-like paired testes. Each testis is composed of a secretory epithelium, which occupies their medio-ventral regions, and of a germinative epithelium situated in the latero-dorsal parts of testes together with large somatic cells. The germ cells are represented on sections by spermatogonia, spermatocytes, early, middle and late spermatids, and mature spermatozoa. Spermatocytes and spermatids contain two centrioles, which disappear afterwards, and a small Golgi-like structure forming an acrosomal cistema. Mature spermatozoa, which lie both within the meshes of somatic cells and also free in the lumen of testes, are compact oval aflagellate cells provided with peripheral channels. They also contain an acrosome, flattened between the cell membrane and the round electron-dense chromatin body, an oval body of lesser density lying in close proximity to the chromatin body, and a group of 5–7 mitochondria with spherically arranged cristae situated immediately behind the nuclear bodies. An acrosomal filament may be sometimes seen beneath the acrosome in the middle spermatids and disappears in the mature spermatozoa. These findings show that the mode of differentiation and pattern of organization of the male sex cells in trombiculid mites are of rather primitive type compared with other acarine spermatozoa.     

Assessment of the Effect of Mesh Density on the Material Property Discretisation Within QCT Based FE Models: A Practical Example Using the Implanted Proximal Tibia

A three-dimensional, quantitative computed tomography based finite element model of a proximal implanted tibia was analysed in order to assess the effect of mesh density on material property discretisation and the resulting influence on the predicted stress distribution. The mesh was refined on the contact surfaces (matched meshes) with element sizes of 3, 2, 1.4, 1 and 0.8 mm. The same loading conditions were used in all models (bi-condylar load: 60% medial, 40% lateral). Significant variations were observed in the modulus distributions between the coarsest and finest mesh densities. Poor discretisation of the material properties also resulted in poor correlations of the stresses and risk ratios between the coarsest and finest meshes. Little difference in Young's modulus, von Mises stress and risk ratio distributions were observed between the three finest models; hence, it was concluded that for this particular case an element size of 1.4 mm on the contact surfaces was enough to properly describe the stiffness, stress and risk ratio distributions within the bone. Poor convergence of the material property distribution occurred when the element size was significantly larger than the pixel size of the source CT data. It was concluded that unless there is convergence in the Young's modulus distribution, convergence of the stress field or of other parameters of interest will not occur either.     

人工半骨盆假体置换联合腰椎椎弓根螺钉固定术后生物力学的有限元分析

目的:建立人工半骨盆假体置换与联合腰椎椎弓根螺钉固定后的三维有限元模型,评价腰骶段生物力学改变后半骨盆假体力学结构的特点。方法:采用CT薄层扫描采集原始数据,分别建立正常骨盆、半骨盆假体置换术后以及半骨盆假体置换联合腰椎椎弓根螺钉固定术后骨盆的三维有限元模型,分别在第4腰椎上终板平面施以500 N的垂直纵向载荷,分析不同骨盆模型的应力分布特点。结果:与正常骨盆有限元模型相比,半骨盆假体置换术后健侧骨盆应力分布以骶髂关节、髋臼窝及耻骨为主,置换侧半骨盆假体以耻骨连接棒、髋臼杯及髂骨座为主,最大应力出现在耻骨连接棒,应力峰值为65.62 MPa。联合腰椎椎弓根螺钉固定后健侧应力相对减小,置换侧髂骨固定座与骶骨固定处应力相对减小,应力分布以腰椎椎弓根钉棒、耻骨连接棒及髋臼杯为主,最大应力出现在椎弓根螺钉,应力峰值为107 MPa。结论:半骨盆假体置换联合腰椎椎弓根螺钉固定后钉棒分担了半骨盆置换后健侧骨盆及置换侧髂骨固定座与骶骨固定处附近的部分应力,缓解应力集中现象,降低术后骨盆破坏风险,一定程度上增加了半骨盆置换后骨盆的稳定性。