bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynein Pulls Microtubules Without Rotating Its Stalk
Authors: Ueno H. , Yasunaga T. , Shingyoji C. , Yamaguchi T. , Hirose K.
Published: July 2013

Dynein is a motor protein that hydrolyses ATP and moves toward the minus end of a microtubule (MT). A dynein molecule has one to three heavy chains, each consisting of three domains: a head, a stalk and a tail. ATP is bound and hydrolysed in the head, which has a ring-like structure composed of 6 AAA+ domains. The stalk is an antiparallel coiled-coil, 10–15 nm long, and has a nucleotide-dependent MT-binding domain at the tip (1) (Fig. 1). It has been proposed that the nucleotide-dependent binding affinity of the tubulin-binding site at the tip of the stalk is modulated by the two alpha helices in the coiled-coil sliding over each other (2). However, it is not known how a dynein molecule moves along a microtubule (MT).
Hybrid Computational Methods for Analysis of AFM Indentation on Mechanically Heterogeneous Samples
Authors: Azeloglu Evren U. , Kaushik Gaurav , Costa Kevin D.
Published: July 2013

Micro-heterogeneity of biological tissue arises from the multiplicity of components that make up the extracellular matrix (ECM) and the constituent cells. Components that have distinct mechanical properties will fundamentally impact the distribution of mechanical stress in the local cellular environment, ultimately determining how physical forces are transferred between macro and micro scales [1]. Atomic force microscope (AFM) indentation is well suited for probing heterogeneities in cell and tissue micromechanics [2], though subsequent data analysis assumes a mechanically homogeneous substrate. While some constituents can be experimentally isolated before testing, reconstructing the equivalent properties of the composite material remains a challenge. When experimental deconstruction is not possible, computational methods can provide an alternative solution. Herein, we introduce a hybrid method of indentation analysis that utilizes Eshelby’s homogenization theory [3] in conjunction with finite element modeling, to computationally deconstruct the material properties of the underlying components within a mechanically heterogeneous sample.
Biomechanical and Microstructural Properties of Fibulin-5 Null Mice
Authors: Wan William , Yanagisawa Hiromi , Gleason Rudolph L.
Published: July 2013

Fibulin-5 is an extracellular matrix (ECM) protein that interacts with integrins and plays a critical role in organizing elastic fibers. Gross observation and histological examination reveal that carotid arteries from fibulin-5 knockout (fib5-/-) mice have disrupted elastic lamellae and are more tortuous [1]. The properties of fibulin-5 null mice provide a unique platform for developing constituent based models for vascular mechanics. While numerous models for blood vessels exist, there is a need to relate measurable microstructural metrics of structurally-based constitutive relations. We performed mechanical tests on carotid arteries from wildtype (WT) and fib5-/-mice and imaged live vessels under multiple loading scenarios to quantify microstructure during deformation. We also fit experimental results to a constitutive relation based on Holzapfel’s model [2]. These results provide a basis for further model development.
0–1-D Multi-Scale Modeling and Numerical Simulation of the Human Cardiovascular System
Authors: Liang Fuyou , Takagi Shu , Liu Hao
Published: July 2013

Arterial pulse has been recognized from antiquity as the most fundamental sign of life. In clinical practice, cardiovascular diseases are often diagnosed and the effects of therapy monitored and evaluated on the basis of interpretation of arterial pulse characteristics. However, the precise components of arterial pulse that best predict the risk of cardiovascular diseases yet remain a subject of considerable debate.
FEM Modeling of Patient-Specific AAA Treated With Endografts
Authors: Meyer Clark A. , Moore James E.
Published: July 2013

Abdominal aortic aneurysm (AAA) rupture occurs when wall stress exceeds wall strength. Endografts aim to prevent rupture by reducing wall stress. However, after implantation, AAA may shrink, grow, or stabilize in diameter, even in the absence of apparent flow into the sac or pressurization. This may result in graft failure through loss of seal, kinking, or component separation. Insight from models of treated AAA could provide insight into treatment methods/limitations and for device design. The nature of the stress reduction in AAA by endograft treatment was modeled using FEM in two patients followed at three time points each (pre-treatment, early follow-up, and late follow-up) — one with a “stable” aneurysm and one with a “shrinking” aneurysm.
The Movement Analysis of Caregivers for Transferring of Disabled Person From Wheelchair to Car Seat
Authors: Kim Yongchul , Kim Younghyun , Yang Youngseon , Park Woochul , Rhee Kunmin
Published: July 2013

The aim of this study was to examine the influence of seat height on the movement of caregiver for transferring of a disabled person from wheelchair to car seat. Five female volunteers served as caregivers; two persons with disabilities and one health volunteer served as passive disabled person. To analyze the movement of a caregiver, we measured the activities of six muscles with surface electrodes and joint angle responses of the hip and knee with electrical goniometers. The caregivers performed transferring task at three different seat heights (400, 500 and 600mm from the floor) in order to investigate the effects of a car seat on transferring movement of a people with disability. From the experimental results, when caregivers were putting a disabled person down a seat, the hip and knee joint angles were decreased 31.9% and 24.7% in 600mm seat height than 400mm seat height, respectively. The integrated EMG activity of erector spinae was decreased 16.3% in 600mm seat height, compared with 500mm seat height. However, the integrated EMG activity of rectus femoris for lower limb in 600mm seat height was increased 33.3% than 500mm seat height.
Deformation Controlled Load Application in Heart Valve Tissue Engineering
Authors: Kortsmit Jeroen , Rutten Marcel C. M. , Wijlaars Marcel W. , Baaijens Frank P. T.
Published: July 2013

Mechanical behavior of tissue-engineered heart valves still needs improvement when native aortic valves are considered as a benchmark [1]. Research showed that mechanical stimulation of tissue-engineered heart valves improved tissue properties [2], although a complete understanding of the effect of loading on tissue development has not been established yet.
Assessing the Potential of Flat-Panel Fluoroscopy CT to Quantify Vertebral Trabecular Architecture In Vivo
Authors: Mulder Lars , van Rietbergen Bert , Noordhoek Niels , Ito Keita
Published: July 2013

Osteoporosis is an affection of the skeleton in elderly leading to loss of bone mass and strength and, consequently, to an increased bone fracture risk. Such fractures can have dramatic consequences for the patient and it has been stated that the prevention of fractures should be the primary goal. This, in turn, requires an accurate diagnosis of bone strength. Presently, the diagnosis of bone strength is merely based on measurements of bone mass using DXA. It is known, however, that the measurement of bone mass alone is not a very accurate predictor for patient-specific bone strength.
Effects of Plaque on Carotid Wall Deformation Studied Using a Finite Element Model
Authors: De Schryver Thomas , Kips Jan , Swillens Abigail , Segers Patrick
Published: July 2013

It is well established that atherosclerosis alters the biomechanics of the arterial wall. In more advanced stages of the disease, atherosclerosis leads to formation of plaques, which can cause life-threatening events such as stroke or myocardial infarction when they rupture. The carotid artery is of special interest when screening patients for cardiovascular disease because of its superficial nature, which makes it easy to study with ultrasound. In addition, as it is particularly susceptible to plaque formation, it is a potential source of stroke. A lot of research effort is dedicated to the identification of plaques prone to rupture (the vulnerable plaque), using invasive (for coronary) and non-invasive ultrasound techniques for superficial arteries such as the carotid. As these vulnerable plaques can not be distinguished from stable plaques on a pure morphological basis other indices have to be found. It is commonly believed that detailed analysis of stresses and strains in the vessel wall may provide the necessary information to make this distinction.
Analysis of Biomechanical Forces Influencing Atherosclerotic Plaque Vulnerability
Authors: Aronis Ze’ev , Einav Shmuel
Published: July 2013

Cardiovascular disease has long been the leading cause of death in the western world: over 1.4 million heart attacks are suffered every year, more than half of which prove fatal. Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. The rupture of thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. The mechanism or mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to a life threatening athero-thrombotic lesion are not fully understood. It has been widely assumed that plaque morphology is the major determinant of clinical outcome [1, 2].
An Anisotropic Structural Model of the Aortic Wall Based on Tensile Tests and Non-Invasive 3D Fibre Analysis Using Diffusion Tensor Imaging
Authors: Flamini Vittoria , Kerskens Christian , Lally Caitríona
Published: July 2013

In recent years, a strong link between the failure of the aortic anatomical structure and the development of cardiovascular diseases has become more evident [1]. Aortas, like arteries in general, can be regarded as anisotropic structures, due to the presence of fibres oriented at an angle within the arterial wall.
A Numerical Model of Adhesion Property of Malaria Infected Red Blood Cells in Micro Scale Blood Flows
Authors: Imai Yohsuke , Kondo Hitoshi , Kang Young Ho , Ishikawa Takuji , Lim Chwee Teck , Yamaguchi Takami
Published: July 2013

Infection by malaria parasite changes mechanical properties of red blood cells (RBCs). Infected red blood cells (IRBCs) lose the deformability but also develop the ability to cytoadhere and rosetting. These outcomes can lead to microvascular blockage [1]. The stiffness of IRBCs [2] and its effects on the flow in micro channels [3] were studied with recent experimental techniques. The cytoadherence and rosetting properties of IRBCs have also been studied experimentally. The cytoadherence is mediated by the interaction of the parasite protein PfEMP1 with several endothelial adhesion molecules, such as CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) [4]. In particular, the ligand-receptor interaction between PfEMP1 and CD36 shows tight adhesion [5]. Microvascular blockage may be a hemodynamic problem, involving the interactions between IRBCs, healthy RBCs (HRBCs) and endothelial cells (ECs) in flowing blood, but however experimental techniques have several limitations to this topic. First, it is still difficult to observe the RBC behavior interacting with many other cells even with the recent confocal microscopy. Second, the three-dimensional information on flow field is hardly obtained. Third, capillaries in human body are circular channels with complex geometry, but such complex channels cannot be created in micro scale. Instead, numerical modeling can overcome these problems. We presented a two-dimensional hemodynamic model involving adhesive interactions [6]. In this paper, we propose a three-dimensional model of the adhesive interactions for micro scale hemodynamics in malaria infection.
Injectable Hyaluronic Acid Hydrogels to Attenuate Post-Infarction Left Ventricular Remodeling
Authors: Ifkovits Jamie L. , Tous Elena , Morita Masato , Gorman Joseph H. , Gorman Robert C. , Burdick Jason A.
Published: July 2013

Several investigators have been successful in reducing the adverse left ventricular (LV) remodeling and expansion that exists in response to myocardial infarction (MI) via the use of various restraints, such as knitted polypropylene meshes [1] and injectable materials [2]. A recent finite element model simulation of the theoretical impact of injection of a material into the myocardium after MI confirmed the suspected stress reduction potential of intramyocardial infarct stiffening with an acellular, non-contractile material. As peak LV wall stress has been implicated in the pathogenesis of post-infarct LV remodeling, this approach to LV wall stress reduction has significant therapeutic potential [3].
5-Hydroxytryptamine and Cyclic Stretch Results in Altered Aortic Valve Collagen Content: Implications for Valve Structure and Function
Authors: Balachandran Kartik , Padala Muralidhar , Chester Adrian , Yoganathan Ajit
Published: July 2013

Cardiac valve structure, function and mechanics are known to be regulated by mechanical forces, cell-mediated factors, as well as circulating endogenous mediators [1]. While several studies have focused on the independent effects of each of these factors, few studies have investigated their combined effects. We sought to understand the combined synergistic effects of cyclic stretch and serotonin on aortic valve structure and function.
Finite Element Modeling of the Tubular Embryonic Chick Heart With Smoothed Surfaces and Contact With Splanchnopleure Membrane
Authors: Yao Jiang , Young Jonathan M. , Filas Benjamen A. , Klinkenberg Nils , Wang Jincheng , Taber Larry A. , Perucchio Renato
Published: July 2013

During cardiac development, the initially straight heart tube bends ventrally and rotates towards the right side of the embryo. The biomechanical mechanism of cardiac looping is still unclear, but it has been hypothesized to be related to the unbalanced forces in the left and right omphalomesenteric veins (OVs) generated by cytoskeletal contraction and cell migration, as well as contact with the Splanchnopleure (SPL), a membrane which is located at the ventral surface of the heart and wraps around the OV at the anterior intestinal portal (AIP) [1]. To test this hypothesis, a computational model is a powerful tool. The objective of this study is to generate a finite element model (FEM) with realistic geometry of the tubular heart with the OVs in its caudal ends, which contacts with the SPL. In alternative to the voxel based model, as explored by Young et al. [2], we study issues related to a model with smoothed surfaces, and its capacity in dealing with nonlinear material, large deformation and contact. Although heart looping proceeds normally without pressure generated from heart beat [3], we applied an internal pressure to test the model.
Dynamic Instability of Arteries: Effects of Perivascular Tissue
Authors: Rachev Alexander , Gleason Rudolph
Published: July 2013

To accomplish their physiological function, arteries have to remain patent under physiological loads, exhibit sufficient mechanical strength, and be capable of preserving their configuration with a sufficient reserve of safety. The latter requirement means that an artery has to be a mechanically stable structure. Among possible patterns of loss of stability is a global beam-like instability of arterial segments of sufficiently large length/diameter ratio. There are data from in vitro experiments that showed that a straight arterial segment can buckle under appropriate combinations of internal pressure and longitudinal stretch ratio and a few mathematical models were addresses to predict this phenomenon (cf. [1]). Conclusions from these studies were extended to explain the origin of arterial tortuosity observed in vivo that might be associated with serious arterial disorders such as atherosclerosis and hypertension. However, in the living organism arteries are subjected to periodic pressure, and therefore data from static experiments and conclusions from mathematical models using the static criterion for instability, namely the occurrence of bifurcation of equilibrium configuration termed as buckling, cannot be directly related to the response of arteries in vivo. A mathematical model for studying dynamic stability of arteries subjected to a longitudinal extension and a periodic pressure was proposed recently [2]. The dynamic criterion for instability was used, based on analyzing the small transverse vibrations of the vessel considered as a straight beam. Though generalization of the model to include the effect of perivascular tissue was discussed, no analysis had been performed in [2]. The objective of this study is to build a predictive model for examining mechanical stability of relatively long arterial segments subjected to a periodic pressure and longitudinal stretch with an account for the effects of perivascular tissue. The occurrence of instability is interpreted as a plausible cause of certain vascular disorders.
Novel Vaginal Transducer for Monitoring Intra-Abdominal Pressure During Physical Activity
Authors: Johnson Paul J. , Rosenbluth Evan M. , Nygaard Ingrid E. , Parikh Monir K. , Hitchcock Robert W.
Published: July 2013

Pelvic floor disorders among women have become increasingly prevalent [1]. In an attempt to minimize incidence, progression and recurrence of pelvic floor disorders, doctors commonly advise women at risk to refrain from physical exertion based on the supposition that certain physical activities significantly raise intra-abdominal pressure (IAP). These activity restrictions are life altering and can vary from doctor to doctor because there is much uncertainty as to which activities truly increase IAP to a harmful level. Previous studies attempting to correlate physical activity with IAP have been limited to conventional urodynamics transducers which are not ideal for IAP measurement during physical activity.
Image-Based Navigation Improves the Accuracy and Reproducibility of Humeral Component Positioning in Total Elbow Arthroplasty
Authors: McDonald Colin P. , Johnson James A. , Peters Terry M. , King Graham J. W.
Published: July 2013

Total elbow arthroplasty (TEA) is commonly employed for cases of humeral bone loss. Success of the procedure depends on both the surgical technique and implant design. Current surgical techniques in TEA generally employ visual cues for estimating the flexion-extension (FE) axis. However, it has been shown that this approach can result in alignment errors upwards of 10° [1]. Computer-assisted orthopaedic surgery (CAOS) employed at the hip and knee has led to an improvement in the accuracy and reproducibility of the procedure, with implant alignment errors approaching 2–3 degrees [2]. TEA may well benefit from the accuracy of CAOS.
Inhomogeneous and Nonlinear Transverse Tensile Properties and Fiber Alignment of Human Supraspinatus Tendon
Authors: Lake Spencer P. , Miller Kristin S. , Kadlowec Jennifer A. , Elliott Dawn M. , Soslowsky Louis J.
Published: July 2013

Rotator cuff tears may be due in part to the complex loading environment of the supraspinatus tendon (SST). Previous research has reported inhomogeneous uniaxial tensile mechanical properties of human SST [1–2] and location-specific collagen fiber alignment distributions that are qualitatively more disperse than other tendons [3–4]. Our group recently measured fiber alignment under load of samples tested along the tendon long-axis and found that re-alignment occurs in the toe-region and varies by SST location [5]. However, the mechanical properties and effect of fiber alignment under more complex loads remain unknown. Examining the properties of SST when tested transverse to the tendon long-axis will evaluate tissue anisotropy and better elucidate possible mechanisms for tissue inhomogeneity and nonlinearity. Therefore, the objectives of this study are to 1) measure local fiber alignment during transverse tensile loading, 2) measure corresponding mechanical properties, and 3) examine structure-function relationships of SST. We hypothesize that 1) fibers will become less aligned during transverse testing, 2) mechanical properties will be greatest in the anterior and bursal locations, and 3) higher initial alignment will correspond to lower transverse tensile properties.
Large Strain Behavior of Brain Tissue: Mechanical Testing and Preliminary Modeling
Authors: Prévost Thibault , Balakrishnan Asha , Socrate Simona
Published: July 2013

Understanding the mechanical response of brain tissue to dynamic loading conditions is critically needed for the development of realistic brain injury models. The characterization of the tissue behavior via mechanical testing and numerical modeling remains, however, challenging because of the strongly nonlinear time- and strain-dependencies inherent in the tissue response. While several studies [1–4] have uncovered some essential features of this response, the integration of all these features — nonlinearities, hysteresis, volumetric behavior — into one single constitutive framework remains an area of active research [5].
Targeted Enzyme-Specific Molecular MR Imaging of Focal Catheter-Induced Vacscular Injury
Authors: DeLeo Michael J. , Gounis Matthew J. , Wakhloo Ajay K. , Bogdanov Alexei A.
Published: July 2013

Catheter-induced vascular injury is a complication of endovascular neurosurgery that may have serious consequences. Other than gross vessel dissection and / or perforation, vessel damage is not visible using standard digital biplane fluoroscopy. Furthermore, the molecular environment in the damaged vessel wall is largely unknown. Recent studies have implicated inflammatory changes in the damaged vessel wall, including upregulation of the key inflammatory mediator NF-kappa-B [1]. Other mediators of inflammation, such as tissue inhibitors of matrix metalloproteinases, are upregulated following arterial de-endothelialization [2]. The enzyme myeloperoxidase (MPO) is known to play significant roles in the progression of vascular pathologies such as atherosclerosis. However, it is unknown whether MPO is involved in catheter-induced vascular injury. In this study, we performed feasibility experiments in an attempt to detect areas of vascular injury using the paramagnetic MR MPO-specific contrast agent, di-5-HT-GdDTPA, which has been shown to be sensitive and specific for MPO both in vitro and in vivo.
Asymmetric Loading Promotes Early Signs of Intervertebral Disc Degeneration in Large Animal Organ Culture
Authors: Korecki Casey L. , Walter Benjamin A. , Godburn Karolyn E. , Iatridis James C.
Published: July 2013

Intervertebral disc (IVD) degeneration is a complex pathology, involving alterations in mechanical and biological function. Mechanical injury to IVDs may contribute to the development of IVD degeneration, and can arise following excessive loading or repeated exposure to loading levels which are not instantaneously damaging. Lateral bending and flexion produced the highest maximum shear strains in human IVDs and are considered the motions that place the IVD at greatest risk of injury (1). The biological response of the IVD to combined bending and compression has been examined in vivo in rat and mouse tail bending models demonstrating structural disruption, apoptosis and remodeling (2,4). However, there are practical limitations to current in vivo studies, as it can be difficult to apply repeated bending loads to the disc in vivo, and few large animal models exist capable of tracking the early biological, structural and compositional changes from asymmetrical loading. IVD organ culture allows control over mechanical boundary conditions and investigation of cellular responses to loading while the IVD remains largely intact, and allows the use of large animal models which more closely mimic the nutritional and compositional nature of human IVDs.
Optimization of an Idealized Y-Graft for the Fontan Procedure Using CFD and a Derivative-Free Optimization Algorithm
Authors: Yang Weiguang , Feinstein Jeffrey A. , Reddy V. Mohan , Marsden Alison L.
Published: July 2013

The Fontan procedure is a surgery performed to treat patients with single ventricle congenital heart defects. The Fontan is the final of three surgical stages. The first stage consists of aortic reconstruction, in a Norwood procedure or variant thereof. In the second stage, the Bidirectional Glenn procedure, the superior vena cava (SVC) is disconnected from the heart and redirected into the pulmonary arteries (PAs). In the third and final stage, the inferior vena cava (IVC) is connected to PAs via a straight Gore-Tex tube, forming a T-shaped junction. Although early survival rates following the Fontan procedure can exceed 90%, significant morbidity remains after surgery including venous hemodynamic abnormalities, diminished exercise capacity, thromboembolic complications, protein-losing enteropathy, heart transplant etc. [1].
An Analytical Model Describing Intervertebral Disc Mechanics Following a Needle Puncture Injury
Authors: Michalek Arthur J. , Iatridis James C.
Published: July 2013

There is growing acceptance of needle puncture injury to induce intervertebral disc (IVD) degeneration in small animal models, and needle injection is the most likely pathway for delivery of growth factors and/or cell therapies to IVDs. Consequently, there is strong motivation for improved understanding of how needle injuries affect IVD mechanics. Loss of disc height and stiffness have been shown following needle puncture [1,2,3], yet the exact mechanisms by which a needle puncture alters disc mechanics are unclear. This study aims to develop an analytical model of the IVD which may be used to assess the relative contributions of various load carriage mechanisms to overall disc properties.
Image-Based Simulation for the Mechanical Characterization of Scaffolds
Authors: Notarberardino Bruno , Young Philippe G. , Hao Liang , Raymont David R. , Turner Irene G. , Harkara Ashwani
Published: July 2013

Recent development of high resolution imaging modalities such as Micro-CT allow realistic porous structures to be straightforwardly and accurately scanned with sub-micron image resolutions possible on some commercially available systems. Combined with novel meshing techniques, these imaging techniques allow for robust and rapid conversion of the 3D scan data into finite element and finite volume meshes which can straightforwardly be used to characterize the response [1]. In addition, various image processing tools allow for interesting sensitivity analyses to be carried out helping to elucidate relationships between key architectural parameters, such as rib thickness, and bulk properties. A number of studies will be shown which demonstrate the ease with which fidelic models of the complex micro-architectures of bio-scaffolds can be generated.
Control of Neural Lineage Differentiation in an Alginate Encapsulation Microenvironment via Cellular Aggregation
Authors: Li Lulu , Davidovich Alexander , Schloss Jennifer , Chippada Uday , Schloss Rene , Langrana Noshir , Yarmush Martin
Published: July 2013

Cell replacement therapies, which utilize renewable stem cell sources, hold tremendous potential to treat a wide range of degenerative diseases. Although many studies have established techniques to successfully differentiate stem cells into different mature cell lineages, their practicality is limited by the lack of control during the differentiation process and low yields of differentiated cells. In order to address these issues, we have previously established a murine embryonic stem cell alginate-poly-L-lysine microencapsulation differentiation system [1]. We demonstrated that ES cell differentiation could be mediated by cell-cell aggregation in the encapsulation microenvironment. We have demonstrated that both cell aggregation and hepatocyte functions, such as urea and albumin secretions, as well as increased expression of cytokeratin 18 and cyp4507a, occur concomitantly with surface E-cadherin expression [2]. In the present studies, we assessed the feasibility of inducing neuronal lineage differentiation in the alginate microenvironment by incorporating soluble inducers, such as retinoic acid, into the permeable microcapsule system. We demonstrated decreased cell aggregation and enhanced neuronal lineage differentiation with the expression of various neuronal specific markers, including neurofilament, A2B5, O1 and glial fibrillary acidic protein (GFAP). In addition, we demonstrated that, by blocking the cell aggregation using anti-E-cadherin antibody, encapsulated cells increased neuronal marker expression at a later stage of the encapsulation, even in the absence of retinoic acid. In conjunction with the mechanical and physical characterizations of the alginate crosslinking network, we show that 2.2% alginate concentration is most conducive to neuronal differentiation from embryonic stem cells in the presence of retinoic acid.
Plaque Rupture in the Carotid Artery: A Combined Imaging, Computational and Histological Analysis
Authors: Soloperto Giulia , Keenan Niall , Sheppard Mary , Wood Nigel , Pennell Dudley J. , Mohiaddin Raad , Xu Xiao Yun
Published: July 2013

Cerebro-vascular events are often related to the rupture of vulnerable atherosclerotic plaques and thrombus formation in the carotid arteries. Haemodynamically significant stenoses experience increased wall shear stress (WSS) in the entrance region but in the post-stenotic region, instead the flow decelerates and tends to become unstable, with separation and recirculation. The high WSS tends to promote processes leading to matrix degradation, with potential rupture, whilst processes stimulated in the post-stenotic zone might be expected to promote further plaque development [1].
Turbulent and Direct Numerical Simulations for Optimizing Mechanical Heart Valve Designs
Authors: Xenos Michalis , Alemu Yared , Einav Shmuel , Bluestein Danny
Published: July 2013

Patients who receive mechanical heart valve (MHV) implants require mandatory anticoagulation medication after MHV implantation due to the thrombogenic potential of the devise. Optimization of MHV designs may facilitate in reducing the flow induced thrombogenic potential. To accomplish this goal highly resolved 3D geometries of different bileaflet mechanical heart valves were examined to study the contribution of distinct flow phases to platelet damage. Both turbulent and direct numerical simulations (DNS) were conducted and compared. A multiphase approach was formulated, in which the blood interacts with a large number of particles injected in the fluid domain, representing the platelets passing through the MHV. Loading histories experienced by the platelets were calculated by computing the combined effect of stress and exposure time. Platelet stress accumulation during randomized repetitive passages past the valves were calculated using a damage accumulation model. The results from the simulations were used as an input to our hemodynamic shearing device (HSD) which emulated the numerical loading waveforms, and platelet activity measured in order to quantify the thrombogenic potential of different MHVs.
Age Effects on Arterial Axial Stiffness in Wild Type and Diabetic Mice
Authors: Wang Ying , Snipes Jennifer S. , Anderson Kevin , Sutton Michael A. , Baxter Sarah C. , Lessner Susan M.
Published: July 2013

The risk of cardiovascular disease is high in both type 1 and type 2 diabetes mellitus, making it the main cause of death due to these diseases.[1] A significant part of this increased risk is thought to be directly linked to pathological changes in mechanical response resulting in vascular dysfunction. Mechanical response can be altered by changes in the geometry of the vessel, such as fibrotic thickening of the vascular wall, as well as by disease linked mechanisms affecting the material microstructure, such as non-specific cross-linking of collagen, which is most often evidenced by an increase in the stiffness of the tissue.[2]
A Hyperelastic Model With Distributed Fibers to Describe Human Supraspinatus Tendon Tensile Mechanics
Authors: Kadlowec Jennifer A. , Lake Spencer P. , Miller Kristin S. , Soslowsky Louis J. , Elliott Dawn M.
Published: July 2013

Tendon tissue is composed of collagen fibers in a hydrated proteoglycan matrix. Although many tendons have fibers that are highly aligned (e.g. flexor tendon), the supraspinatus tendon (SST) of the shoulder has significant distribution of fiber alignment [1]. The alignment and distribution of the fibers likely contributes to the nonlinear and anisotropic mechanical behavior, however this has not been demonstrated. Understanding the role of fiber structure on tendon mechanical behavior, that is, characterizing the structure-function relationships, is critical to evaluate the function of injured, degenerated, or healing tendons and would be invaluable in the design and assessment of tissue engineered tendon replacements. While a structurally based hyperelastic model has been developed for tendon [2], this model contained only a single fiber orientation, which is not adequate for the more distributed fiber structure in the SST. We have recently applied a hyperelastic model formulation that has distributed collagen fiber orientation developed by Gasser and colleagues for the arterial wall [3] to model a tendon analog made from nanofibrous scaffolds [4]. The objective of this study was to build on previous work to apply a hyperelastic fiber-reinforced constitutive model that includes a specific term for fiber distribution to the tensile mechanics of human SST and to evaluate the site-specific model material properties.
Redox Signaling in an In Vivo Murine Model of Tailored Wall Shear Stress
Authors: Willett Nick J. , Oshinski John , Giddens Don , Guldberg Robert , Taylor W. Robert
Published: July 2013

Wall Shear Stress (WSS) has been identified as an important factor in the pathogenesis of atherosclerosis. We developed a novel murine aortic coarctation model to alter the hemodynamic environment in vivo. The model utilizes the shape memory response of nitinol clips to provide a high degree of control over aortic diameter and subsequently WSS. We employed this model to test the hypothesis that acute changes in WSS in vivo induce upregulation of inflammatory proteins mediated by Reactive Oxygen Species (ROS). WSS was mapped through a computational fluid dynamic model and correlated to inflammatory marker expression. C57B16 control mice were compared to tempol treated, apocynin treated, p47phox KO, and catalase overexpressor mice in this study. The results show that the coarctation produces low mean oscillatory WSS in the region downstream of the clip. The WSS in this region correlates to a large increase in VCAM-1 expression in wild-type mice. This WSS dependent increase in protein expression is unchanged in animal models of decreased ROS. This suggests that although the redox state is important to the overall pathogenesis of the disease, individual ROS or ROS sources may not be sufficient to inhibit a WSS dependent inflammatory response. Further analysis with this model utilizing other reagent treatments, transgenic mice, and markers will allow us to analyze the functional contribution of transcription factors, ROS, and ROS sources to WSS dependent inflammatory protein expression.
Influence of Calcified Cartilage Zone Permeability in Mechanical Behavior of Articular Cartilage: A Finite Element Study
Authors: Vahdati Ali , Wagner Diane R.
Published: July 2013

Articular cartilage (AC) disease and especially osteoarthrithis (OA) are debilitating conditions that are associated with huge social and economic burdens. To understand the factors involved in initiation and progression of OA, the mechanical state of the cartilage tissue must be first understood [1]. Biphasic and triphasic models developed by Mow and coworkers relate AC structure with its mechanical behavior and provided researchers with valuable models for AC biomechanics [2, 3]. Although much is known about AC and its mechanical properties, the zone of calcified cartilage (ZCC) has been sparsely studied. ZCC is very thin and highly interdigitated with subchondral bone (SB) which makes it very difficult to isolate for independent study [4]. It is well known that SB plays an important role in both initiation and/or progression of OA [5], thus ZCC may also be an important player in the pathology of the disease [6]. A few studies have investigated mechanical properties of ZCC, but conflicting results have been published on ZCC permeability. Although ZCC has been mainly assumed to be impermeable [7], recently Hwang et al. [8] suggested that ZCC may have even higher permeability than cartilage itself. We studied the effect of ZCC permeability on mechanical behavior of AC using a finite element (FE) model.
The Influence of Material Properties and Geometry on Optic Nerve Head Biomechanics
Authors: Yang Hongli , Sigal Ian A. , Roberts Michael D. , Burgoyne Claude F. , Downs J. Crawford
Published: July 2013

Glaucoma is the second leading cause of irreversible blindness in the world. The biological mechanisms of this disease are not well understood, and the factors contributing to its progression are not well characterized. It is generally accepted that the retinal ganglion cell axons are damaged in glaucoma as they pass through the optic nerve head (ONH). The ONH contains the lamina cribrosa (LC), a fenestrated connective tissue network that spans the scleral canal, through which the axons pass as they leave the eye. It has been postulated that intraocular pressure (IOP)-related stress and strain plays a central role in the pathophysiology of glaucoma [1], so the study of LC biomechanics is important in developing an understanding of the disease.
A Continuous-Discrete Mathematical Model Simulates In Vitro Angiogenesis
Authors: Sibole Scott C. , Underwood Clayton J. , Guilkey James E. , Weiss Jeffrey A.
Published: July 2013

Angiogenesis plays a pivotal role in formative life stages such as embryogenesis, tissue remodeling such as wound healing, and in pathological conditions such as excessive proliferation of blood vessels in tumorigenesis. In all cases, angiogenesis consistently follows a sequence beginning with detachment and migration of endothelial cells from existing vasculature and ending with formation of a new vessel network. This process is influenced by chemical and mechanical factors. While the chemical processes governing angiogenesis have been studied extensively and are still an active topic for research, the mechanical aspects have received less attention [1].
Noninvasive Surface Wave Method for Measuring Skin Viscoelasticity
Authors: Zhang Xiaoming , Kinnick Randall R. , Pittelkow Mark R. , Osborn Thomas G. , Greenleaf James F.
Published: July 2013

Characterization of the viscoelastic mechanical properties of skin is important for improving accurate medical examination and diagnosis of disorders involving cutaneous and subcutaneous tissues; more thoroughly understanding skin biophysical and physiological properties; identifying normal and abnormal skin aging and disease processes; developing and applying improved pharmacologic and other therapeutic interventions; as well as cosmetic applications. Several noninvasive methods have been developed for measurement of mechanical properties of skin [1]. However, most methods measure a stiffness parameter but not the material properties of skin. For example, the suction method measures the displacement of skin in response to suction. The measurement is dependent on the aperture and fixation of probes and also difficult to interpret.
Biomechanics of the Posterior Pole During the Remodeling Progression From Normal to Early Experimental Glaucoma
Authors: Sigal Ian A. , Yang Hongli , Roberts Michael D. , Burgoyne Claude F. , Downs J. Crawford
Published: July 2013

Glaucoma is one of the leading causes of blindness worldwide. The loss of vision associated with glaucoma is due to damage to the retinal ganglion cell axons, which transmit visual information to the brain. Damage to these axons is believed to occur as the axons pass through the lamina cribrosa (LC), a connective tissue structure in the optic nerve head at the back of the eye. Elevated intraocular pressure (IOP) has been identified as the main risk factor for the development of the neuropathy, but the mechanism(s) by which a mechanical insult (elevated IOP) is translated into a biological effect (glaucomatous optic neuropathy) is not well understood.
Mechano-Rheological Properties of the Murine Thrombus Determined via Nanoindentation and Finite Element Modeling
Authors: Slaboch Constance L. , Ovaert Timothy C.
Published: July 2013

Deep vein thrombosis (DVT) is the formation of a thrombus, or blood clot, in one of the extremities, often in the vein of a leg. Approximately 2 million incidences of DVT occur annually [1]. Roughly 300,000 people die due to the development of a pulmonary embolism (PE), which occurs when the thrombus from a DVT relocates to the pulmonary artery. Abdominal aortic aneurysm (AAA) is another life-threatening disease involving thrombi, resulting in 15,000 deaths annually. Increased life expectancy raises significant concern for AAA, as it generally affects people age 55 and older. Together, these diseases impinge over 2.5 million people each year. Determining the mechanical properties of thrombi, which can be platelet- and/or fiber-rich, and understanding how they dissociate or fail mechanically under fluid flow conditions, can help diagnose these diseases at an earlier stage in their progression, thereby providing time to initiate treatments. In addition, increased knowledge of thrombi properties can lead to the development of preventative drug therapies. Both of these outcomes have the potential to decrease the number of deaths from the aforementioned diseases.
Graphic User Interface for a Human Circulation Model
Authors: Schneider Nigel R. , Cecchetti Jason , Wu Yi
Published: July 2013

Numerical simulations are important tools for understanding the human circulation system in different states of heart failure and exercise, or with a cardiac assist device. However, its application is limited due to the complexity of the numerical model of the human circulation system. To overcome this difficulty, a Graphic User Interface (GUI) has been developed. The GUI was designed to be intuitive; users can set different scenarios using self-explanatory controls, without knowledge of the tasks done in the complex numerical model. The GUI will display the simulated hemodynamic response of the model. This GUI may be used for both education and medical/research purposes.
Gait Prediction Using Concurrent Musculoskeletal Control and FE Simulations
Authors: Halloran Jason P. , Ackermann Marko , Erdemir Ahmet , van den Bogert Antonie J.
Published: July 2013

Current computational methods of simulating activities of daily living (ADL) have primarily consisted of musculoskeletal simulations [1]. Due to computational expense, simulations generally include assumptions which simplify joint or soft-tissue behavior. Joints are modeled as hinge or spherical and soft-tissue effects are included as spring-dashpot systems. Incorporating detailed deformable soft-tissue models would help overcome simplifying assumptions by coupling the behavior of a muscle loaded model with the underlying structures. Important clinical applications for a multi-domain simulation framework include, but are hardly limited to, predicting modifications to ADL to compensate for osteoarthritic pain or minimizing peak plantar pressures, which are believed to be significant for diabetic foot ulceration.
High Glucose Alters Endothelial Cell Response to Shear Stress
Authors: Kemeny Steven F. , Clyne Alisa Morss
Published: July 2013

Endothelial cells line the walls of all blood vessels, where they maintain homeostasis through control of vascular tone, permeability, inflammation, and the growth and regression of blood vessels. Endothelial cells are mechanosensitive to fluid shear stress, elongating and aligning in the flow direction [1–2]. This shape change is driven by rearrangement of the actin cytoskeleton and focal adhesions [2]. Hyperglycemia, a hallmark of diabetes, affects endothelial cell function. High glucose has been shown to increase protein kinase C, formation of glucose-derived advanced glycation end-products, and glucose flux through the aldose reductase pathway within endothelial cells [3]. These changes are thought to be related to increased reactive oxygen species production [4]. While endothelial cell mechanics have been widely studied in healthy conditions, many disease states have yet to be explored. Biochemical alterations related to high glucose may alter endothelial cell mechanics.
Traumatic Injury: Mechanical Response of Porcine Liver Tissue Under High Strain Rate Compression Testing
Authors: Chen Joseph , Priddy Lauren B. , Prabhu Raj , Marin Esteban , Williams Lakiesha , Horstemeyer Mark , Liao Jun
Published: July 2013

The injury metrics for dummies in car crash scenarios are typically force and acceleration; however, real injuries in humans are characterized by damage and fracture (rupture) processes of internal tissues and organs. An accurate prediction of the risk of these injuries using modeling and simulation requires knowledge of the mechanical properties of different human tissues/organs under various loading conditions. Especially in high-impact situations, quasi-static biomechanics may not be sufficient in characterizing the actual mechanical response of a tissue; therefore, high-strain rate testing becomes an area of interest [1].
Validation of a New Finite Element Model for Human Knee Ligaments for Use in High Speed Automotive Collisions
Authors: Silvestri Chiara , Peck Louis R. , Billiar Kristen L. , Ray Malcolm H.
Published: July 2013

A finite element model of knee human ligaments was developed and validated to predict the injury potential of occupants in high speed frontal automotive collisions. Dynamic failure properties of ligaments were modeled to facilitate the development of more realistic dynamic representation of the human lower extremities when subjected to a high strain rate. Uniaxial impulsive impact loads were applied to porcine medial collateral ligament-bone complex with strain rates up to145 s−1. From test results, the failure load was found to depend on ligament geometric parameters and on the strain rate applied. The information obtained was then integrated into a finite element model of the knee ligaments with the potential to be used also for representation of ligaments in other regions of the human body. The model was then validated against knee ligament dynamic tolerance tests found in literature. Results obtained from finite element simulations during the validation process agreed with the outcomes reported by literature findings encouraging the use of this ligament model as a powerful and innovative tool to estimate ligament human response in high speed frontal automotive collisions.
Quantifying the Spatial Variation of Lower-Limb Soft Tissue Artefact During Functional Activity Using MR Imaging and X-Ray Fluoroscopy
Authors: Akbarshahi Massoud , Fernandez Justin W. , Schache Anthony , Baker Richard , Banks Scott , Pandy Marcus G.
Published: July 2013

Non-rigid movement of the soft tissue interface between skin-mounted markers and the underlying bones, also known as soft tissue artifact (STA), poses a major limitation to the non-invasive estimation of joint kinematics using three-dimensional (3D) motion analysis systems. Thorough knowledge of the nature of this non-rigid behavior is essential for development of compensation algorithms to enhance the accuracy of these systems. The studies in the literature aimed at quantifying STA have implemented invasive measurement methods such as bone pins [1] and external fixator devices [2], or have used subjects with pathological conditions [3]. In the present study, we integrated Magnetic Resonance (MR) and X-ray imaging techniques to evaluate the non-rigid behavior of the lower-limb soft tissue of healthy adults for a number of different functional tasks.