Tailoring the mechanical properties by molecular integration of flexible and stiff polymer networks.

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Wan, Haixiao; Shen, Jianxiang; Gao, Naishen; Liu, Jun; Gao, Yangyang; Zhang, Liqun

2018-03-28

Designing a multiple-network structure at the molecular level to tailor the mechanical properties of polymeric materials is of great scientific and technological importance. Through the coarse-grained molecular dynamics simulation, we successfully construct an interpenetrating polymer network (IPN) composed of a flexible polymer network and a stiff polymer network. First, we find that there is an optimal chain stiffness for a single network (SN) to achieve the best stress-strain behavior. Then we turn to study the mechanical behaviors of IPNs. The result shows that the stress-strain behaviors of the IPNs appreciably exceed the sum of that of the corresponding single flexible and stiff network, which highlights the advantage of the IPN structure. By systematically varying the stiffness of the stiff polymer network of the IPNs, optimal stiffness also exists to achieve the best performance. We attribute this to a much larger contribution of the non-bonded interaction energy. Last, the effect of the component concentration ratio is probed. With the increase of the concentration of the flexible network, the stress-strain behavior of the IPNs is gradually enhanced, while an optimized concentration (around 60% molar ration) of the stiff network occurs, which could result from the dominant role of the enthalpy rather than the entropy. In general, our work is expected to provide some guidelines to better tailor the mechanical properties of the IPNs made of a flexible network and a stiff network, by manipulating the stiffness of the stiff polymer network and the component concentration ratio.

The role of focal adhesion kinase in the regulation of cellular mechanical properties

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2013-01-01

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation. (paper)

The role of focal adhesion kinase in the regulation of cellular mechanical properties

Science.gov (United States)

Mierke, Claudia Tanja

2013-12-01

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

KAUST Repository

Li, YZ

2014-08-01

Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

Matrix Stiffness Corresponding to Strictured Bowel Induces a Fibrogenic Response in Human Colonic Fibroblasts

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Johnson, Laura A.; Rodansky, Eva S.; Sauder, Kay L.; Horowitz, Jeffrey C.; Mih, Justin D.; Tschumperlin, Daniel J.; Higgins, Peter D.

2013-01-01

Background Crohn’s disease is characterized by repeated cycles of inflammation and mucosal healing which ultimately progress to intestinal fibrosis. This inexorable progression towards fibrosis suggests that fibrosis becomes inflammation-independent and auto-propagative. We hypothesized that matrix stiffness regulates this auto-propagation of intestinal fibrosis. Methods The stiffness of fresh ex vivo samples from normal human small intestine, Crohn’s disease strictures, and the unaffected margin were measured with a microelastometer. Normal human colonic fibroblasts were cultured on physiologically normal or pathologically stiff matrices corresponding to the physiological stiffness of normal or fibrotic bowel. Cellular response was assayed for changes in cell morphology, α-smooth muscle actin (αSMA) staining, and gene expression. Results Microelastometer measurements revealed a significant increase in colonic tissue stiffness between normal human colon and Crohn’s strictures as well as between the stricture and adjacent tissue margin. In Ccd-18co cells grown on stiff matrices corresponding to Crohn’s strictures, cellular proliferation increased. Pathologic stiffness induced a marked change in cell morphology and increased αSMA protein expression. Growth on a stiff matrix induced fibrogenic gene expression, decreased matrix metalloproteinase and pro-inflammatory gene expression, and was associated with nuclear localization of the transcriptional cofactor MRTF-A. Conclusions Matrix stiffness, representative of the pathological stiffness of Crohn’s strictures, activates human colonic fibroblasts to a fibrogenic phenotype. Matrix stiffness affects multiple pathways suggesting the mechanical properties of the cellular environment are critical to fibroblast function and may contribute to autopropagation of intestinal fibrosis in the absence of inflammation, thereby contributing to the intractable intestinal fibrosis characteristic of Crohn’s disease. PMID

Penetration of sulfur hexafluoride into cellular polypropylene films and its effect on the electric charging and electromechanical response of ferroelectrets

International Nuclear Information System (INIS)

Qiu Xunlin; Wegener, Michael; Wirges, Werner; Zhang Xiaoqing; Hillenbrand, Joachim; Xia Zhongfu; Gerhard-Multhaupt, Reimund; Sessler, Gerhard M

2005-01-01

Cellular polypropylene (PP) films were treated with sulfur hexafluoride (SF 6 ) gas in order to study the SF 6 penetration behaviour and optimize the electric charging conditions. There were differences in the penetration of SF 6 for different cellular PP materials, depending on the microscopic properties, which manifest themselves in the voided structure as well as in the mechanical stiffnesses of the cellular films. The penetration of SF 6 after long-term pressure treatment is confirmed in strongly inflated cellular PP films with a low mechanical stiffness of about 1 MPa. No SF 6 penetration occurs for slightly inflated cellular PP films with smaller void sizes and higher mechanical stiffnesses of around 5.8 MPa. The observed thickness variations, the higher charging fields during corona charging because of SF 6 penetration and the SF 6 environment, as well as the resulting electromechanical properties are discussed

A computational and cellular solids approach to the stiffness-based design of bone scaffolds.

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Norato, J A; Wagoner Johnson, A J

2011-09-01

We derive a cellular solids approach to the design of bone scaffolds for stiffness and pore size. Specifically, we focus on scaffolds made of stacked, alternating, orthogonal layers of hydroxyapatite rods, such as those obtained via micro-robotic deposition, and aim to determine the rod diameter, spacing and overlap required to obtain specified elastic moduli and pore size. To validate and calibrate the cellular solids model, we employ a finite element model and determine the effective scaffold moduli via numerical homogenization. In order to perform an efficient, automated execution of the numerical studies, we employ a geometry projection method so that analyses corresponding to different scaffold dimensions can be performed on a fixed, non-conforming mesh. Based on the developed model, we provide design charts to aid in the selection of rod diameter, spacing and overlap to be used in the robotic deposition to attain desired elastic moduli and pore size.

Origami interleaved tube cellular materials

International Nuclear Information System (INIS)

Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-01-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

Origami interleaved tube cellular materials

Science.gov (United States)

Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-09-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

Effects of mechanical properties and geometric conditions on stiffness of Hyperboloid Shallow Shell

Directory of Open Access Journals (Sweden)

Zhao Lihong

2015-01-01

Full Text Available The experiment models based on the hyperboloid shallow shells that represent automobile panel's surface features are established. The effects of material properties and geometric conditions condition on the stiffness of hyperboloid shallow shell are investigated experimentally. The influences of panel thickness and geometric conditions on stiffness are very obvious. Stiffness increases with increasing of the panel thickness, and stiffness doubled as increasing in thickness with 0.1 mm. The effect of thickness on stiffness is far greater than that of blank holding force. The greater the arc height of punch, the greater the stiffness. And stiffness increases nearly by five times with arc height of punch is from 3mm to 9mm. The effect of arc height of punch on stiffness is far greater than that of materials mechanical properties. The stiffness is varied with different panel material properties by the same forming and stiffness test conditions. The decrease of yield strength is beneficial to the panel stiffness. The appropriate choice of materials and forming process condition is important in meeting necessary requirements for the energy-saving, lightweight and reducing wind resistance design in automotive industry.

Time dependency of morphological remodeling of endothelial cells in response to substrate stiffness

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Goli-Malekabadi, Zahra; Tafazzoli-shadpour, Mohammad; Tamayol, Ali; Seyedjafari, Ehsan

2017-01-01

Introduction: Substrate stiffness regulates cellular behavior as cells experience different stiffness values of tissues in the body. For example, endothelial cells (ECs) covering the inner layer of blood vessels are exposed to different stiffness values due to various pathologic and physiologic conditions. Despite numerous studies, cells by time span sense mechanical properties of the substrate, but the response is not well understood. We hypothesized that time is a major determinant influencing the behavior of cells seeded on substrates of varying stiffness. Methods: We monitored cell spreading, internal structure, 3D topography, and the viability of ECs over 24 hours of culture on polydimethylsiloxane (PDMS) substrates with two different degrees of elastic modulus. Results: Despite significant differences in cell spreading after cell seeding, cells showed a similar shape and internal structure after 24 hours of culture on both soft and stiff substrates. However, 3D topographical images confirmed existence of rich lamellipodia and filopodia around the cells cultured on stiffer PDMS substrates. Conclusion: It was concluded that the response of ECs to the substrate stiffness was time dependent with initial enhanced cellular spreading and viability on stiffer substrates. Results can provide a better comprehension of cell mechanotransduction for tissue engineering applications. PMID:28546952

Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.

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Merna, Nick; Wong, Andrew K; Barahona, Victor; Llanos, Pierre; Kunar, Balvir; Palikuqi, Brisa; Ginsberg, Michael; Rafii, Shahin; Rabbany, Sina Y

2018-04-17

Endothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought to determine the role of endothelial luminal surface stiffness in tissue-specific mechanotransduction of laminar shear stress in microvascular mouse cells and the role of arachidonic acid in mediating this response. Microvascular mouse endothelial cells were subjected to laminar shear stress at 4 dynes/cm 2 for 12 hours in parallel plate flow chambers that enabled real-time optical microscopy and atomic force microscopy measurements of cell stiffness. Lung endothelial cells aligned parallel to flow, while cardiac endothelial cells did not. This rapid alignment was accompanied by increased cell stiffness. The addition of arachidonic acid to cardiac endothelial cells increased alignment and stiffness in response to shear stress. Inhibition of arachidonic acid in lung endothelial cells and embryonic stem cell-derived endothelial cells prevented cellular alignment and decreased cell stiffness. Our findings suggest that increased endothelial luminal surface stiffness in microvascular cells may facilitate mechanotransduction and alignment in response to laminar shear stress. Furthermore, the arachidonic acid pathway may mediate this tissue-specific process. An improved understanding of this response will aid in the treatment of organ-specific vascular disease. © 2018 John Wiley & Sons Ltd.

Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

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Blaesi, Aron H; Saka, Nannaji

2016-07-25

At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

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Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3high cells, whereas the invasiveness of β3 specific knock

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3 high cells but not in αvβ3 low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3 low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock

A novel mechatronic system for measuring end-point stiffness: mechanical design and preliminary tests.

Science.gov (United States)

Masia, L; Sandini, G; Morasso, P G

2011-01-01

Measuring arm stiffness is of great interest for many disciplines from biomechanics to medicine especially because modulation of impedance represents one of the main mechanism underlying control of movement and interaction with external environment. Previous works have proposed different methods to identify multijoint hand stiffness by using planar or even tridimensional haptic devices, but the associated computational burden makes them not easy to implement. We present a novel mechanism conceived for measuring multijoint planar stiffness by a single measurement and in a reduced execution time. A novel mechanical rotary device applies cyclic radial perturbation to human arm of a known displacement and the force is acquired by means of a 6-axes commercial load cell. The outcomes suggest that the system is not only reliable but allows obtaining a bi-dimensional estimation of arm stiffness in reduced amount of time and the results are comparable with those reported in previous researches. © 2011 IEEE

Mechanical properties of two-way grid shells optimized considering roundness and elastic stiffness

International Nuclear Information System (INIS)

Ogawa, Toshiyuki; Yuta, Nishikawa; Rie, Tateishi; Ohsaki, Makoto

2002-01-01

A single-layer two-way grid shell defined by Bezier surface is optimized by coordinates of the control points as design variables. The purpose of this paper is to find optimal shapes considering roundness and elastic stiffness, and to investigate their mechanical properties. The distance of the center of curvature from the specified point is used for formulating the objective function for generating a round shape. Consider next a problem of minimizing the compliance as mechanical performance measure. The compliance is defined by the external work against the static loads applied to the nodes. The mechanically optimal shape is different from the round shape. Therefore, the multi objective optimization problem is formulated for optimizing the two objectives, which are roundness and the elastic stiffness defined by using the compliance. The constraint method is used for obtaining Pareto optimal solutions between the two objectives. We optimize single-layer two-way grid shells with square and rectangle plans. Mechanical properties of the optimal shapes are investigated by compliance and the distributions of axial force and bending moment. The round shape is significantly dominated by the bending moment and its compliance is large. The bending moment of the mechanically optimal shape is not very large, and the latticed shell has large stiffness through axial deformation. A trade-off shape is round enough, and the influence of the bending moment is smaller than that of the optimal round shape and the elastic stiffness is moderately large

Influence of Crosslink Density and Stiffness on Mechanical Properties of Type I Collagen Gel

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Shengmao Lin

2015-02-01

Full Text Available The mechanical properties of type I collagen gel vary due to different polymerization parameters. In this work, the role of crosslinks in terms of density and stiffness on the macroscopic behavior of collagen gel were investigated through computational modeling. The collagen fiber network was developed in a representative volume element, which used the inter-fiber spacing to regulate the crosslink density. The obtained tensile behavior of collagen gel was validated against published experimental data. Results suggest that the cross-linked fiber alignment dominated the strain stiffening effect of the collagen gel. In addition, the gel stiffness was enhanced approximately 40 times as the crosslink density doubled. The non-affine deformation was reduced with the increased crosslink density. A positive bilinear correlation between the crosslink density and gel stiffness was obtained. On the other hand, the crosslink stiffness had much less impact on the gel stiffness. This work could enhance our understanding of collagen gel mechanics and shed lights on designing future clinical relevant biomaterials with better control of polymerization parameters.

Self-reported knee joint instability is related to passive mechanical stiffness in medial knee osteoarthritis.

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Creaby, Mark W; Wrigley, Tim V; Lim, Boon-Whatt; Hinman, Rana S; Bryant, Adam L; Bennell, Kim L

2013-11-20

Self-reported knee joint instability compromises function in individuals with medial knee osteoarthritis and may be related to impaired joint mechanics. The purpose of this study was to evaluate the relationship between self-reported instability and the passive varus-valgus mechanical behaviour of the medial osteoarthritis knee. Passive varus-valgus angular laxity and stiffness were assessed using a modified isokinetic dynamometer in 73 participants with medial tibiofemoral osteoarthritis. All participants self-reported the absence or presence of knee instability symptoms and the degree to which instability affected daily activity on a 6-point likert scale. Forward linear regression modelling identified a significant inverse relationship between passive mid-range knee stiffness and symptoms of knee instability (r = 0.27; P 0.05). Conceivably, a stiffer passive system may contribute toward greater joint stability during functional activities. Importantly however, net joint stiffness is influenced by both active and passive stiffness, and thus the active neuromuscular system may compensate for reduced passive stiffness in order to maintain joint stability. Future work is merited to examine the role of active stiffness in symptomatic joint stability.

Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness

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Pongkitwitoon, Suphannee; Uzer, Gunes; Rubin, Janet; Judex, Stefan

2016-10-01

Mesenchymal stem cells (MSC) responding to mechanical cues generated by physical activity is critical for skeletal development and remodeling. Here, we utilized low intensity vibrations (LIV) as a physiologically relevant mechanical signal and hypothesized that the confined cytoskeletal configuration imposed by 2D culture will enable human bone marrow MSCs (hBMSC) to respond more robustly when LIV is applied in-plane (horizontal-LIV) rather than out-of-plane (vertical-LIV). All LIV signals enhanced hBMSC proliferation, osteogenic differentiation, and upregulated genes associated with cytoskeletal structure. The cellular response was more pronounced at higher frequencies (100 Hz vs 30 Hz) and when applied in the horizontal plane. Horizontal but not vertical LIV realigned the cell cytoskeleton, culminating in increased cell stiffness. Our results show that applying very small oscillatory motions within the primary cell attachment plane, rather than perpendicular to it, amplifies the cell’s response to LIV, ostensibly facilitating a more effective transfer of intracellular forces. Transcriptional and structural changes in particular with horizontal LIV, together with the strong frequency dependency of the signal, emphasize the importance of intracellular cytoskeletal configuration in sensing and responding to high-frequency mechanical signals at low intensities.

Discrete computational mechanics for stiff phenomena

KAUST Repository

Michels, Dominik L.

2016-11-28

Many natural phenomena which occur in the realm of visual computing and computational physics, like the dynamics of cloth, fibers, fluids, and solids as well as collision scenarios are described by stiff Hamiltonian equations of motion, i.e. differential equations whose solution spectra simultaneously contain extremely high and low frequencies. This usually impedes the development of physically accurate and at the same time efficient integration algorithms. We present a straightforward computationally oriented introduction to advanced concepts from classical mechanics. We provide an easy to understand step-by-step introduction from variational principles over the Euler-Lagrange formalism and the Legendre transformation to Hamiltonian mechanics. Based on such solid theoretical foundations, we study the underlying geometric structure of Hamiltonian systems as well as their discrete counterparts in order to develop sophisticated structure preserving integration algorithms to efficiently perform high fidelity simulations.

Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.

Directory of Open Access Journals (Sweden)

Raimon Sunyer

Full Text Available Many fundamental cell processes, such as angiogenesis, neurogenesis and cancer metastasis, are thought to be modulated by extracellular matrix stiffness. Thus, the availability of matrix substrates having well-defined stiffness profiles can be of great importance in biophysical studies of cell-substrate interaction. Here, we present a method to fabricate biocompatible hydrogels with a well defined and linear stiffness gradient. This method, involving the photopolymerization of films by progressively uncovering an acrylamide/bis-acrylamide solution initially covered with an opaque mask, can be easily implemented with common lab equipment. It produces linear stiffness gradients of at least 115 kPa/mm, extending from ∼1 kPa to 240 kPa (in units of Young's modulus. Hydrogels with less steep gradients and narrower stiffness ranges can easily be produced. The hydrogels can be covalently functionalized with uniform coatings of proteins that promote cell adhesion. Cell spreading on these hydrogels linearly correlates with hydrogel stiffness, indicating that this technique effectively modifies the mechanical environment of living cells. This technique provides a simple approach that produces steeper gradients, wider rigidity ranges, and more accurate profiles than current methods.

Substrate stiffness promotes latent TGF-β1 activation in hepatocellular carcinoma

International Nuclear Information System (INIS)

Pang, Mingshu; Teng, Yao; Huang, Jianyong; Yuan, Yuan; Lin, Feng; Xiong, Chunyang

2017-01-01

Hepatocellular carcinoma (HCC) was usually coupled with increased stiffness of the extracellular matrix (ECM) and elevated level of transforming growth factor-β1 (TGF-β1). However, the mechanism by which substrate rigidity modulated TGF-β1 signaling transduction remained unknown. This paper investigated the molecular mechanism of how matrix stiffness regulating TGF-β1 signaling in HCC cells. By means of stiffness tunable collagen I-coated polyacrylamide (PA) gels, we found that the expressions of β1 integrin, p-FAK Y397 and p-Smad2 upregulated on stiffer gels as well as the content of TGF-β1 in culture media of HCC cells, which were inhibited by RGD blocking peptides, Y-27632 (ROCK inhibitor) or Blebbistatin (myosin II inhibitor). Cellular traction force was also significantly higher when plated on stiffer substrates but dramatically decreased after treatment with Y-27632 or Blebbistatin. Furthermore, the upregulation of p-Smad2 in the HCC cells on stiffer PA gels induced by exogenetic latent TGF-β1 was downregulated in the presence of RGD peptides. The nuclear translocation of Smad2 induced by latent TGF-β1 was inhibited by Y-27632 or Blebbistatin. Our results suggested that the extracellular matrix stiffness regulated latent TGF-β1 activation by cytoskeletal tension in HCC cells, showing that matrix stiffness was a key regulator involving the TGF-β1 activity in HCC cells. The current study presented a mechanism of how hepatocirrhosis developed into liver cancer. - Highlights: • TGF-β1 signaling pathway regulated by ECM stiffness was studied in hepatocellular carcinoma. • Matrix stiffness promoted latent TGF-β1 activation via β1 integrin-FAK-Rho GTPase pathway. • A mechanism of how hepatocirrhosis developed into liver cancer was presented.

Mechanical characterization of journal superconducting magnetic bearings: stiffness, hysteresis and force relaxation

International Nuclear Information System (INIS)

Cristache, Cristian; Valiente-Blanco, Ignacio; Diez-Jimenez, Efren; Alvarez-Valenzuela, Marco Antonio; Perez-Diaz, Jose Luis; Pato, Nelson

2014-01-01

Superconducting magnetic bearings (SMBs) can provide stable levitation without direct contact between them and a magnetic source (typically a permanent magnet). In this context, superconducting magnetic levitation provides a new tool for mechanical engineers to design non-contact mechanisms solving the tribological problems associated with contact at very low temperatures. In the last years, different mechanisms have been proposed taking advantage of superconducting magnetic levitation. Flywheels, conveyors or mechanisms for high-precision positioning. In this work the mechanical stiffness of a journal SMBs have been experimentally studied. Both radial and axial stiffness have been considered. The influence of the size and shape of the permanent magnets (PM), the size and shape of the HTS, the polarization and poles configuration of PMs of the journal SMB have been studied experimentally. Additionally, in this work hysteresis behavior and force relaxation are considered because they are essential for mechanical engineer when designing bearings that hold levitating axles.

Origami-inspired, on-demand deployable and collapsible mechanical metamaterials with tunable stiffness

Science.gov (United States)

Zhai, Zirui; Wang, Yong; Jiang, Hanqing

2018-03-01

Origami has been employed to build deployable mechanical metamaterials through folding and unfolding along the crease lines. Deployable metamaterials are usually flexible, particularly along their deploying and collapsing directions, which unfortunately in many cases leads to an unstable deployed state, i.e., small perturbations may collapse the structure along the same deployment path. Here we create an origami-inspired mechanical metamaterial with on-demand deployability and selective collapsibility through energy analysis. This metamaterial has autonomous deployability from the collapsed state and can be selectively collapsed along two different paths, embodying low stiffness for one path and substantially high stiffness for another path. The created mechanical metamaterial yields load-bearing capability in the deployed direction while possessing great deployability and collapsibility. The principle in this work can be utilized to design and create versatile origami-inspired mechanical metamaterials that can find many applications.

Matrix stiffness reverses the effect of actomyosin tension on cell proliferation.

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Mih, Justin D; Marinkovic, Aleksandar; Liu, Fei; Sharif, Asma S; Tschumperlin, Daniel J

2012-12-15

The stiffness of the extracellular matrix exerts powerful effects on cell proliferation and differentiation, but the mechanisms transducing matrix stiffness into cellular fate decisions remain poorly understood. Two widely reported responses to matrix stiffening are increases in actomyosin contractility and cell proliferation. To delineate their relationship, we modulated cytoskeletal tension in cells grown across a physiological range of matrix stiffnesses. On both synthetic and naturally derived soft matrices, and across a panel of cell types, we observed a striking reversal of the effect of inhibiting actomyosin contractility, switching from the attenuation of proliferation on rigid substrates to the robust promotion of proliferation on soft matrices. Inhibiting contractility on soft matrices decoupled proliferation from cytoskeletal tension and focal adhesion organization, but not from cell spread area. Our results demonstrate that matrix stiffness and actomyosin contractility converge on cell spreading in an unexpected fashion to control a key aspect of cell fate.

Cellular shear stiffness reflects progression of arsenic-induced transformation during G1

DEFF Research Database (Denmark)

Muñoz, Alexandra; Eldridge, Will J; Jakobsen, Nina Munkholt

2017-01-01

epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage independent growth. Shear stiffness of various cell populations in G1 was assessed using...... reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation of the stiffness of Arsenic clones was reduced compared to control clones, as well as to the arsenic exposed cell population. Cell stiffness...

Limit cycles and stiffness control with variable stiffness actuators

NARCIS (Netherlands)

Carloni, Raffaella; Marconi, L.

2012-01-01

Variable stiffness actuators realize highly dynamic systems, whose inherent mechanical compliance can be properly exploited to obtain a robust and energy-efficient behavior. The paper presents a control strategy for variable stiffness actuators with the primarily goal of tracking a limit cycle

Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose.

Science.gov (United States)

Mirahmadi, Fereshteh; Koolstra, Jan Harm; Lobbezoo, Frank; van Lenthe, G Harry; Ghazanfari, Samaneh; Snabel, Jessica; Stoop, Reinout; Everts, Vincent

2018-03-01

Aging is accompanied by a series of changes in mature tissues that influence their properties and functions. Collagen, as one of the main extracellular components of cartilage, becomes highly crosslinked during aging. In this study, the aim was to examine whether a correlation exists between collagen crosslinking induced by artificial aging and mechanical properties of the temporomandibular joint (TMJ) condyle. To evaluate this hypothesis, collagen crosslinks were induced using ribose incubation. Porcine TMJ condyles were incubated for 7 days with different concentrations of ribose. The compressive modulus and stiffness ratio (incubated versus control) was determined after loading. Glycosaminoglycan and collagen content, and the number of crosslinks were analyzed. Tissue structure was visualized by microscopy using different staining methods. Concomitant with an increasing concentration of ribose, an increase of collagen crosslinks was found. The number of crosslinks increased almost 50 fold after incubation with the highest concentration of ribose. Simultaneously, the stiffness ratio of the samples showed a significant increase after incubation with the ribose. Pearson correlation analyses showed a significant positive correlation between the overall stiffness ratio and the crosslink level; the higher the number of crosslinks the higher the stiffness. The present model, in which ribose was used to mimic certain aspects of age-related changes, can be employed as an in vitro model to study age-related mechanical changes in the TMJ condyle. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical metamaterials at the theoretical limit of isotropic elastic stiffness

Science.gov (United States)

Berger, J. B.; Wadley, H. N. G.; McMeeking, R. M.

2017-02-01

A wide variety of high-performance applications require materials for which shape control is maintained under substantial stress, and that have minimal density. Bio-inspired hexagonal and square honeycomb structures and lattice materials based on repeating unit cells composed of webs or trusses, when made from materials of high elastic stiffness and low density, represent some of the lightest, stiffest and strongest materials available today. Recent advances in 3D printing and automated assembly have enabled such complicated material geometries to be fabricated at low (and declining) cost. These mechanical metamaterials have properties that are a function of their mesoscale geometry as well as their constituents, leading to combinations of properties that are unobtainable in solid materials; however, a material geometry that achieves the theoretical upper bounds for isotropic elasticity and strain energy storage (the Hashin-Shtrikman upper bounds) has yet to be identified. Here we evaluate the manner in which strain energy distributes under load in a representative selection of material geometries, to identify the morphological features associated with high elastic performance. Using finite-element models, supported by analytical methods, and a heuristic optimization scheme, we identify a material geometry that achieves the Hashin-Shtrikman upper bounds on isotropic elastic stiffness. Previous work has focused on truss networks and anisotropic honeycombs, neither of which can achieve this theoretical limit. We find that stiff but well distributed networks of plates are required to transfer loads efficiently between neighbouring members. The resulting low-density mechanical metamaterials have many advantageous properties: their mesoscale geometry can facilitate large crushing strains with high energy absorption, optical bandgaps and mechanically tunable acoustic bandgaps, high thermal insulation, buoyancy, and fluid storage and transport. Our relatively simple

Statistical mechanics of cellular automata

International Nuclear Information System (INIS)

Wolfram, S.

1983-01-01

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

Origami tubes assembled into stiff, yet reconfigurable structures and metamaterials.

Science.gov (United States)

Filipov, Evgueni T; Tachi, Tomohiro; Paulino, Glaucio H

2015-10-06

Thin sheets have long been known to experience an increase in stiffness when they are bent, buckled, or assembled into smaller interlocking structures. We introduce a unique orientation for coupling rigidly foldable origami tubes in a "zipper" fashion that substantially increases the system stiffness and permits only one flexible deformation mode through which the structure can deploy. The flexible deployment of the tubular structures is permitted by localized bending of the origami along prescribed fold lines. All other deformation modes, such as global bending and twisting of the structural system, are substantially stiffer because the tubular assemblages are overconstrained and the thin sheets become engaged in tension and compression. The zipper-coupled tubes yield an unusually large eigenvalue bandgap that represents the unique difference in stiffness between deformation modes. Furthermore, we couple compatible origami tubes into a variety of cellular assemblages that can enhance mechanical characteristics and geometric versatility, leading to a potential design paradigm for structures and metamaterials that can be deployed, stiffened, and tuned. The enhanced mechanical properties, versatility, and adaptivity of these thin sheet systems can provide practical solutions of varying geometric scales in science and engineering.

Trabecular meshwork stiffness in glaucoma.

Science.gov (United States)

Wang, Ke; Read, A Thomas; Sulchek, Todd; Ethier, C Ross

2017-05-01

Alterations in stiffness of the trabecular meshwork (TM) may play an important role in primary open-angle glaucoma (POAG), the second leading cause of blindness. Specifically, certain data suggest an association between elevated intraocular pressure (IOP) and increased TM stiffness; however, the underlying link between TM stiffness and IOP remains unclear and requires further study. We here first review the literature on TM stiffness measurements, encompassing various species and based on a number of measurement techniques, including direct approaches such as atomic force microscopy (AFM) and uniaxial tension tests, and indirect methods based on a beam deflection model. We also briefly review the effects of several factors that affect TM stiffness, including lysophospholipids, rho-kinase inhibitors, cytoskeletal disrupting agents, dexamethasone (DEX), transforming growth factor-β 2 (TGF-β 2 ), nitric oxide (NO) and cellular senescence. We then describe a method we have developed for determining TM stiffness measurement in mice using a cryosection/AFM-based approach, and present preliminary data on TM stiffness in C57BL/6J and CBA/J mouse strains. Finally, we investigate the relationship between TM stiffness and outflow facility between these two strains. The method we have developed shows promise for further direct measurements of mouse TM stiffness, which may be of value in understanding mechanistic relations between outflow facility and TM biomechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanotransduction mechanisms in growing spherically structured tissues

Science.gov (United States)

Littlejohns, Euan; Dunlop, Carina M.

2018-04-01

There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

Coupling between the Output Force and Stiffness in Different Variable Stiffness Actuators

Directory of Open Access Journals (Sweden)

Amir Jafari

2014-08-01

Full Text Available The fundamental objective in developing variable stiffness actuators is to enable the actuator to deliberately tune its stiffness. This is done through controlling the energy flow extracted from internal power units, i.e., the motors of a variable stiffness actuator (VSA. However, the stiffness may also be unintentionally affected by the external environment, over which, there is no control. This paper analysis the correlation between the external loads, applied to different variable stiffness actuators, and their resultant output stiffness. Different types of variable stiffness actuators have been studied considering springs with different types of nonlinearity. The results provide some insights into how to design the actuator mechanism and nonlinearity of the springs in order to increase the decoupling between the load and stiffness in these actuators. This would significantly widen the application range of a variable stiffness actuator.

Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

Science.gov (United States)

Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

2015-06-01

Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs. Copyright © 2015 the American Physiological Society.

Chorein Sensitivity of Actin Polymerization, Cell Shape and Mechanical Stiffness of Vascular Endothelial Cells

Directory of Open Access Journals (Sweden)

Ioana Alesutan

2013-09-01

Full Text Available Background/Aims: Endothelial cell stiffness plays a key role in endothelium-dependent control of vascular tone and arterial blood pressure. Actin polymerization and distribution of microfilaments is essential for mechanical cell stiffness. Chorein, a protein encoded by the VPS13A gene, defective in chorea-acanthocytosis (ChAc, is involved in neuronal cell survival as well as cortical actin polymerization of erythrocytes and blood platelets. Chorein is expressed in a wide variety of further cells, yet nothing is known about the impact of chorein on cells other than neurons, erythrocytes and platelets. The present study explored whether chorein is expressed in human umbilical vein endothelial cells (HUVECs and addressed the putative role of chorein in the regulation of cytoskeletal architecture, stiffness and survival of those cells. Methods: In HUVECs with or without silencing of the VPS13A gene, VPS13A mRNA expression was determined utilizing quantitative RT-PCR, cytoskeletal organization visualized by confocal microscopy, G/F actin ratio and phosphorylation status of focal adhesion kinase quantified by western blotting, cell death determined by flow cytometry, mechanical properties studied by atomic force microscopy (AFM and cell morphology analysed by scanning ion conductance microscopy (SICM. Results: VPS13A mRNA expression was detectable in HUVECs. Silencing of the VPS13A gene attenuated the filamentous actin network, decreased the ratio of soluble G-actin over filamentous F-actin, reduced cell stiffness and changed cell morphology as compared to HUVECs silenced with negative control siRNA. These effects were paralleled by a significant decrease in FAK phosphorylation following VPS13A silencing. Moreover, silencing of the VPS13A gene increased caspase 3 activity and induced necrosis in HUVECs. Conclusions: Chorein is a novel regulator of cytoskeletal architecture, cell shape, mechanical stiffness and survival of vascular endothelial cells.

Modeling and simulating the neuromuscular mechanisms regulating ankle and knee joint stiffness during human locomotion.

Science.gov (United States)

Sartori, Massimo; Maculan, Marco; Pizzolato, Claudio; Reggiani, Monica; Farina, Dario

2015-10-01

This work presents an electrophysiologically and dynamically consistent musculoskeletal model to predict stiffness in the human ankle and knee joints as derived from the joints constituent biological tissues (i.e., the spanning musculotendon units). The modeling method we propose uses electromyography (EMG) recordings from 13 muscle groups to drive forward dynamic simulations of the human leg in five healthy subjects during overground walking and running. The EMG-driven musculoskeletal model estimates musculotendon and resulting joint stiffness that is consistent with experimental EMG data as well as with the experimental joint moments. This provides a framework that allows for the first time observing 1) the elastic interplay between the knee and ankle joints, 2) the individual muscle contribution to joint stiffness, and 3) the underlying co-contraction strategies. It provides a theoretical description of how stiffness modulates as a function of muscle activation, fiber contraction, and interacting tendon dynamics. Furthermore, it describes how this differs from currently available stiffness definitions, including quasi-stiffness and short-range stiffness. This work offers a theoretical and computational basis for describing and investigating the neuromuscular mechanisms underlying human locomotion. Copyright © 2015 the American Physiological Society.

Use of Guided Acoustic Waves to Assess the Effects of Thermal-Mechanical Cycling on Composite Stiffness

Science.gov (United States)

Seale, Michael D.; Madaras, Eric I.

2000-01-01

The introduction of new, advanced composite materials into aviation systems requires it thorough understanding of the long-term effects of combined thermal and mechanical loading. As part of a study to evaluate the effects of thermal-mechanical cycling, it guided acoustic (Lamb) wave measurement system was used to measure the bending and out-of-plane stiffness coefficients of composite laminates undergoing thermal-mechanical loading. The system uses a pulse/receive technique that excites an antisymmetric Lamb mode and measures the time-of-flight over a wide frequency range. Given the material density and plate thickness, the bending and out-of-plane shear stiffnesses are calculated from a reconstruction of the velocity dispersion curve. A series of 16 and 32-ply composite laminates were subjected to it thermal-mechanical loading profile in load frames equipped with special environmental chambers. The composite systems studied were it graphite fiber reinforced amorphous thermoplastic polyimide and it graphite fiber reinforced bismaleimide thermoset. The samples were exposed to both high and low temperature extremes its well as high and low strain profiles. The bending and out-of-plane stiffnesses for composite sample that have undergone over 6,000 cycles of thermal-mechanical loading are reported. The Lamb wave generated elastic stiffness results have shown decreases of up to 20% at 4,936 loading cycles for the graphite/thermoplastic samples and up to 64% at 4,706 loading cycles for the graphite/thermoset samples.

Effects of Matrix Alignment and Mechanical Constraints on Cellular Behavior in 3D Engineered Microtissues

Science.gov (United States)

Bose, Prasenjit; Eyckmans, Jeroen; Chen, Christopher; Reich, Daniel

The adhesion of cells to the extracellular matrix (ECM) plays a crucial role in a variety of cellular functions. The main building blocks of the ECM are 3D networks of fibrous proteins whose structure and alignments varies with tissue type. However, the impact of ECM alignment on cellular behaviors such as cell adhesion, spreading, extension and mechanics remains poorly understood. We present results on the development of a microtissue-based system that enables control of the structure, orientation, and degree of fibrillar alignment in 3D fibroblast-populated collagen gels. The tissues self-assemble from cell-laden collagen gels placed in micro-fabricated wells containing sets of elastic pillars. The contractile action of the cells leads to controlled alignment of the fibrous collagen, depending on the number and location of the pillars in each well. The pillars are elastic, and are utilized to measure the contractile forces of the microtissues, and by incorporating magnetic material in selected pillars, time-varying forces can be applied to the tissues for dynamic stimulation and measurement of mechanical properties. Results on the effects of varying pillar shape, spacing, location, and stiffness on microtissue organization and contractility will be presented. This work is supported by NSF CMMI-1463011.

Critical evaluation on structural stiffness of porous cellular structure of cobalt chromium alloy

Science.gov (United States)

Abd Malek, N. M. S.; Mohamed, S. R.; Che Ghani, S. A.; Harun, W. S. Wan

2015-12-01

In order to improve the stiffness characteristics of orthopedic devices implants that mimic the mechanical behavior of bone need to be considered. With the capability of Additive layer manufacturing processes to produce orthopedic implants with tailored mechanical properties are needed. This paper discusses finite element (FE) analysis and mechanical characterization of porous medical grade cobalt chromium (CoCr) alloy in cubical structures with volume based porosity ranging between 60% to 80% produced using direct metal laser sintering (DMLS) process. ANSYS 14.0 FE modelling software was used to predict the effective elastic modulus of the samples and comparisons were made with the experimental data. The effective mechanical properties of porous samples that were determined by uniaxial compression testing show exponential decreasing trend with the increase in porosity. Finite element model shows good agreement with experimentally obtained stress-strain curve in the elastic regions. The models prove that numerical analysis of actual prosthesis implant can be computed particularly in load bearing condition

Critical evaluation on structural stiffness of porous cellular structure of cobalt chromium alloy

International Nuclear Information System (INIS)

Abd Malek, N M S; Mohamed, S R; Che Ghani, S A; Wan Harun, W S

2015-01-01

In order to improve the stiffness characteristics of orthopedic devices implants that mimic the mechanical behavior of bone need to be considered. With the capability of Additive layer manufacturing processes to produce orthopedic implants with tailored mechanical properties are needed. This paper discusses finite element (FE) analysis and mechanical characterization of porous medical grade cobalt chromium (CoCr) alloy in cubical structures with volume based porosity ranging between 60% to 80% produced using direct metal laser sintering (DMLS) process. ANSYS 14.0 FE modelling software was used to predict the effective elastic modulus of the samples and comparisons were made with the experimental data. The effective mechanical properties of porous samples that were determined by uniaxial compression testing show exponential decreasing trend with the increase in porosity. Finite element model shows good agreement with experimentally obtained stress-strain curve in the elastic regions. The models prove that numerical analysis of actual prosthesis implant can be computed particularly in load bearing condition (paper)

Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases.

Science.gov (United States)

Wheeler, Richard; Turner, Robert D; Bailey, Richard G; Salamaga, Bartłomiej; Mesnage, Stéphane; Mohamad, Sharifah A S; Hayhurst, Emma J; Horsburgh, Malcolm; Hobbs, Jamie K; Foster, Simon J

2015-07-28

Most bacterial cells are enclosed in a single macromolecule of the cell wall polymer, peptidoglycan, which is required for shape determination and maintenance of viability, while peptidoglycan biosynthesis is an important antibiotic target. It is hypothesized that cellular enlargement requires regional expansion of the cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that are together required for cell enlargement and correct cellular morphology of Staphylococcus aureus, demonstrating the overall importance of this enzyme activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the explanation of the observed morphological defects in terms of the mechanical and biochemical properties of peptidoglycan. It was shown that cells lacking groups of these hydrolases have increased surface stiffness and, in the absence of SagB, substantially increased glycan chain length. This indicates that, beyond their established roles (for example in cell separation), some hydrolases enable cellular enlargement by making peptidoglycan easier to stretch, providing the first direct evidence demonstrating that cellular enlargement occurs via modulation of the mechanical properties of peptidoglycan. Understanding bacterial growth and division is a fundamental problem, and knowledge in this area underlies the treatment of many infectious diseases. Almost all bacteria are surrounded by a macromolecule of peptidoglycan that encloses the cell and maintains shape, and bacterial cells must increase the size of this molecule in order to enlarge themselves. This requires not only the insertion of new peptidoglycan monomers, a process targeted by antibiotics, including penicillin, but also breakage of existing bonds, a potentially hazardous activity for the cell. Using Staphylococcus aureus, we have identified a set of enzymes that are critical for cellular enlargement. We

Dextran as a fast resorbable and mechanically stiff coating for flexible neural probes

Science.gov (United States)

Kil, D.; Brancato, L.; Puers, R.

2017-11-01

In this paper we report on the use of dextran as a temporary, fast dissolving stiff coating for flexible neural probes. Although polymer-based neural implants offer several advantages, compared to their rigid silicon counterparts, they pose significant challenges during implantation. Due to their extreme flexibility, they have the tendency to buckle under the axial load applied during insertion. The structural stiffness of the implants can be temporarily increased by applying a bioresorbable dextran coating which eases the penetration of neural tissue. For this application three types of dextran with different molecular weights are analysed. The dissolution rate of the coatings is reported as well as the increased bending stiffness resulting from the dextran coating of Parylene C neural probes. Based on these findings the dissolution rate can be linked to parameters such as molecular weight, coating thickness and the surface area exposed to the dissolution medium. The mechanical characterization yields information on how the structural stiffness of neural probes can be tuned by varying the dextran’s molecular weight and coating thickness.

Effect of stiffness modulation on mechanical stability of stretchable a-IGZO TFTs

Science.gov (United States)

Park, Hyungjin; Cho, Kyoungah; Oh, Hyungon; Kim, Sangsig

2018-05-01

In this study, we fabricate the amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) on a stretchable substrate with a buffer stage and investigate the mechanical stability and electrical characteristics when the length of the substrate is stretched by 1.7 times. The buffer stage is responsible for the stiffness modulation of the stretchable substrate. The mobility, the threshold voltage and the on/off ratio of the stretchable a-IGZO TFT are measured to be 18.1 cm2/V·s, 1 V, and 3 × 107, respectively. Our simulation conducted by a three dimensional finite elements method reveals that the stiffness modulation reduces the stress experienced by the substrate in the stretched state by about one-tenth. In addition, the mechanical stability and electrical characteristics of the a-IGZO TFT are maintained even when the substrate is stretched by 1.7 times.

Arterial stiffness and cognitive impairment.

Science.gov (United States)

Li, Xiaoxuan; Lyu, Peiyuan; Ren, Yanyan; An, Jin; Dong, Yanhong

2017-09-15

Arterial stiffness is one of the earliest indicators of changes in vascular wall structure and function and may be assessed using various indicators, such as pulse-wave velocity (PWV), the cardio-ankle vascular index (CAVI), the ankle-brachial index (ABI), pulse pressure (PP), the augmentation index (AI), flow-mediated dilation (FMD), carotid intima media thickness (IMT) and arterial stiffness index-β. Arterial stiffness is generally considered an independent predictor of cardiovascular and cerebrovascular diseases. To date, a significant number of studies have focused on the relationship between arterial stiffness and cognitive impairment. To investigate the relationships between specific arterial stiffness parameters and cognitive impairment, elucidate the pathophysiological mechanisms underlying the relationship between arterial stiffness and cognitive impairment and determine how to interfere with arterial stiffness to prevent cognitive impairment, we searched PUBMED for studies regarding the relationship between arterial stiffness and cognitive impairment that were published from 2000 to 2017. We used the following key words in our search: "arterial stiffness and cognitive impairment" and "arterial stiffness and cognitive impairment mechanism". Studies involving human subjects older than 30years were included in the review, while irrelevant studies (i.e., studies involving subjects with comorbid kidney disease, diabetes and cardiac disease) were excluded from the review. We determined that arterial stiffness severity was positively correlated with cognitive impairment. Of the markers used to assess arterial stiffness, a higher PWV, CAVI, AI, IMT and index-β and a lower ABI and FMD were related to cognitive impairment. However, the relationship between PP and cognitive impairment remained controversial. The potential mechanisms linking arterial stiffness and cognitive impairment may be associated with arterial pulsatility, as greater arterial pulsatility

Measuring the correlation between cell mechanics and myofibroblastic differentiation during maturation of 3D microtissues

Science.gov (United States)

Zhao, Ruogang; Wang, Weigang; Boudou, Thomas; Chen, Christopher; Reich, Daniel

2013-03-01

Tissue stiffness and cellular contractility are two of the most important biomechanical factors regulating pathological transitions of encapsulated cells, such as the differentiation of fibroblasts into myofibroblasts - a key event contributing to tissue fibrosis. However, a quantitative correlation between tissue stiffness and cellular contraction and myofibroblast differentiation has not yet been established in 3D environments, mainly due to the lack of suitable 3D tissue culture models that allow both tissue remodeling and simultaneous measurement of the cell/tissue mechanics. To address this, we have developed a magnetic microtissue tester system that allows the remodeling of arrays of cell-laden 3D collagen microtissues and the measurement of cell and tissue mechanics using magnetically actuated elastomeric microcantilevers. By measuring the development of cell/tissue mechanical properties and the expression level of α-smooth muscle actin (α-SMA, a marker for myofibroblast differentiation) during a 6 day culture period, we found microtissue stiffness increased by 45% and α-SMA expression increased by 38%, but tissue contraction forces only increased by 10%, indicating that tissue stiffness may be the predominant mechanical factor for regulation of myofibroblast differentiation. This study provides new quantitative insight into the regulatory effect of cell and tissue mechanics on cellular function. Supported in part by NIH grant HL090747

Development of ideal solution and validation of stiffness and strength by finite element method for truss-wall corrugated cellular solids

International Nuclear Information System (INIS)

Choi, Jeong Ho; Lee, Jung Hwan; Lee, Je Hyun

2014-01-01

The objective of this study is to find the density, stiffness, and strength of truss-wall unit cell models. The diamond-corrugation, triangular-corrugation, and Navtruss-corrugation models are used for the unit cell. The ideal solutions derived for these are based on solid wall unit cell models and are developed using the Gibson-Ashby theory. To verify the ideal solutions of the models, the density, strength, and stiffness are simulated using ABAQUS software and compared with the ideal solutions on a log-log scale. The material properties of stainless steel 304 are applied. The diameter is 0.5 mm; the opening width is 0.5 mm; and the corrugation angle is 45 .deg. . Consequently, the relative Young's modulus and relative yield strength of the truss-wall unit models are good matches for the ideal expectations. It may be possible to apply a truss-wall model to diverse fields such as transportation or biomedical applications as one of the open-cell cellular solids.

Development of ideal solution and validation of stiffness and strength by finite element method for truss-wall corrugated cellular solids

Energy Technology Data Exchange (ETDEWEB)

Choi, Jeong Ho [Samjung E and W, Changwon (Korea, Republic of); Lee, Jung Hwan [Korea Institute of Materials Science,Changwon (Korea, Republic of); Lee, Je Hyun [Changwon National University, Changwon (Korea, Republic of)

2014-05-15

The objective of this study is to find the density, stiffness, and strength of truss-wall unit cell models. The diamond-corrugation, triangular-corrugation, and Navtruss-corrugation models are used for the unit cell. The ideal solutions derived for these are based on solid wall unit cell models and are developed using the Gibson-Ashby theory. To verify the ideal solutions of the models, the density, strength, and stiffness are simulated using ABAQUS software and compared with the ideal solutions on a log-log scale. The material properties of stainless steel 304 are applied. The diameter is 0.5 mm; the opening width is 0.5 mm; and the corrugation angle is 45 .deg. . Consequently, the relative Young's modulus and relative yield strength of the truss-wall unit models are good matches for the ideal expectations. It may be possible to apply a truss-wall model to diverse fields such as transportation or biomedical applications as one of the open-cell cellular solids.

Cell motility regulation on a stepped micro pillar array device (SMPAD) with a discrete stiffness gradient.

Science.gov (United States)

Lee, Sujin; Hong, Juhee; Lee, Junghoon

2016-02-28

Our tissues consist of individual cells that respond to the elasticity of their environment, which varies between and within tissues. To better understand mechanically driven cell migration, it is necessary to manipulate the stiffness gradient across a substrate. Here, we have demonstrated a new variant of the microfabricated polymeric pillar array platform that can decouple the stiffness gradient from the ECM protein area. This goal is achieved via a "stepped" micro pillar array device (SMPAD) in which the contact area with the cell was kept constant while the diameter of the pillar bodies was altered to attain the proper mechanical stiffness. Using double-step SU-8 mold fabrication, the diameter of the top of every pillar was kept uniform, whereas that of the bottom was changed, to achieve the desired substrate rigidity. Fibronectin was immobilized on the pillar tops, providing a focal adhesion site for cells. C2C12, HeLa and NIH3T3 cells were cultured on the SMPAD, and the motion of the cells was observed by time-lapse microscopy. Using this simple platform, which produces a purely physical stimulus, we observed that various types of cell behavior are affected by the mechanical stimulus of the environment. We also demonstrated directed cell migration guided by a discrete rigidity gradient by varying stiffness. Interestingly, cell velocity was highest at the highest stiffness. Our approach enables the regulation of the mechanical properties of the polymeric pillar array device and eliminates the effects of the size of the contact area. This technique is a unique tool for studying cellular motion and behavior relative to various stiffness gradients in the environment.

Single motor–variable stiffness actuator using bistable switching mechanisms for independent motion and stiffness control

NARCIS (Netherlands)

Groothuis, Stefan; Carloni, Raffaella; Stramigioli, Stefano

This paper presents a proof of concept of a variable stiffness actuator (VSA) that uses only one (high power) input motor. In general, VSAs use two (high power) motors to be able to control both the output position and the output stiffness, which possibly results in a heavy, and bulky system. In

A mechanical model of stereocilia that demonstrates a shift in the high-sensitivity region due to the interplay of a negative stiffness and an adaptation mechanism

International Nuclear Information System (INIS)

Lee, Changwon; Park, Sukyung

2012-01-01

Stereocilia are the basic sensory units of nature's inertial sensors and are highly sensitive over broad dynamic ranges, which is a major challenge in the design of conventional engineering sensors. The high sensitivity that is maintained by stereocilia was hypothesized to exist due to a combination of adaptation and negative stiffness mechanisms, which shift the region of highest sensitivity toward the active operation range of the stereocilia bundle. To examine the adaptation hypothesis in terms of its potential applicability to future applications regarding the design of inertial sensors, we developed a mechanical mimicry of the interplay between negative stiffness and the adaptation of the stereocilia that produces spontaneous oscillation of the hair bundle. The mechanical model consists of an inverted pendulum and a fixed T-bar that mimic the interaction of two adjacent stereocilia. To focus on the interaction of one gating spring and the corresponding adaptation motor without the effect of coupling from the other gating springs attached to the neighboring stereocilia, we fixed one bar that contains the adaptation motor. To emulate the negative resistance of the tip-link due to the transient stiffness softening by the gating ion channel, a magnet pair was attached to the top of the inverted pendulum and the fixed T-bar. Readjustment of the tip-link tension by the ‘slipping down and climbing up’ motion of the adaptation molecular motors was demonstrated by the side-to-side movement of the magnet by a step motor. The negative stiffness region was observed near the equilibrium position and shifted with the activation of the adaptation motor. The temporal demonstration of the stiffness shift was measured as a spontaneous oscillation. The results showed that the interplay between the negative stiffness and the adaptation mechanism was mechanically produced by the combination of a repulsive force and its continuous readjustment and is better understood through a

Cellular mechanics and motility

Science.gov (United States)

Hénon, Sylvie; Sykes, Cécile

2015-10-01

The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

Cellular phone interference with the operation of mechanical ventilators.

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Shaw, Cheryl I; Kacmarek, Robert M; Hampton, Rickey L; Riggi, Vincent; El Masry, Ashraf; Cooper, Jeffrey B; Hurford, William E

2004-04-01

To determine whether a cellular phone would interfere with the operation of mechanical ventilators. Laboratory study. University medical center. Fourteen mechanical ventilators. We evaluated change in operation and malfunction of the mechanical ventilators. The cellular phone (Nokia 6120i) was computer controlled, operating at 828.750 MHz analog modulation. It was operated at 16, 40, 100, 250, and 600 mW, 30 cm from the floor and 30, 15, and ventilator. Six of the 14 ventilators tested malfunctioned when a cellular phone at maximum power output was placed ventilating when the cellular phone at maximum power output was placed ventilator. One ventilator doubled the ventilatory rate and another increased the displayed tidal volume from 350 to 1033 mL. In one of the infant ventilators, displayed tidal volume increased from 21 to 100 mL. In another ventilator, the high respiratory rate alarm sounded but the rate had not changed. In a controlled laboratory setting, cellular phones placed in close proximity to some commercially available intensive care ventilators can cause malfunctions, including irrecoverable cessation of ventilation. This is most likely to occur if the cellular phone is or =3 feet from all medical devices. The current electromagnetic compatibility standards for mechanical ventilators are inadequate to prevent malfunction. Manufacturers should ensure that their products are not affected by wireless technology even when placed immediately next to the device.

Mechanisms and circumvention of cellular resistance to cisplatin.

NARCIS (Netherlands)

Hospers, Geesiena Alberdina Petronella

1989-01-01

Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

Atomic force microscopy stiffness tomography on living Arabidopsis thaliana cells reveals the mechanical properties of surface and deep cell-wall layers during growth.

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Radotić, Ksenija; Roduit, Charles; Simonović, Jasna; Hornitschek, Patricia; Fankhauser, Christian; Mutavdžić, Dragosav; Steinbach, Gabor; Dietler, Giovanni; Kasas, Sandor

2012-08-08

Cell-wall mechanical properties play a key role in the growth and the protection of plants. However, little is known about genuine wall mechanical properties and their growth-related dynamics at subcellular resolution and in living cells. Here, we used atomic force microscopy (AFM) stiffness tomography to explore stiffness distribution in the cell wall of suspension-cultured Arabidopsis thaliana as a model of primary, growing cell wall. For the first time that we know of, this new imaging technique was performed on living single cells of a higher plant, permitting monitoring of the stiffness distribution in cell-wall layers as a function of the depth and its evolution during the different growth phases. The mechanical measurements were correlated with changes in the composition of the cell wall, which were revealed by Fourier-transform infrared (FTIR) spectroscopy. In the beginning and end of cell growth, the average stiffness of the cell wall was low and the wall was mechanically homogenous, whereas in the exponential growth phase, the average wall stiffness increased, with increasing heterogeneity. In this phase, the difference between the superficial and deep wall stiffness was highest. FTIR spectra revealed a relative increase in the polysaccharide/lignin content. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Optimization of a quasi-zero-stiffness isolator

International Nuclear Information System (INIS)

Carrella, A.; Brennan, M. J.; Waters, T. P.

2007-01-01

The frequency range over which a mount can isolate a mass from a vibrating base (or vice versa) is often limited by the mount stiffness required to support the weight of the mass. This compromise can be made more favourable by employing non-linear mounts with a softening spring characteristic such that small excursions about the static equilibrium position result in small dynamic spring forces and a correspondingly low natural frequency. This paper concerns the force-displacement characteristic of a so-called quasi-zero-stiffness (QZS) mechanism which is characterised by an appreciable static stiffness but very small (theoretically zero) dynamic stiffness. The mechanism studied comprises a vertical spring acting in parallel with two further springs which, when inclined at an appropriate angle to the vertical, produce a cancelling negative stiffness effect. Analysis of the system shows that a QZS characteristic can be obtained if the systems parameters (angle of inclination and ratio of spring stiffness) are opportunely chosen. By introducing the additional criterion that the displacement of the system be largest without exceeding a desired (low) value of stiffness an optimal set of parameter values is derived. Under sufficiently large displacements the stiffness of the QZS mechanism can eventually exceed that of the simple mass-spring system and criteria for this detrimental scenario to arise are presented

Modulation of Huh7.5 spheroid formation and functionality using modified PEG-based hydrogels of different stiffness.

Directory of Open Access Journals (Sweden)

Bae Hoon Lee

Full Text Available Physical cues, such as cell microenvironment stiffness, are known to be important factors in modulating cellular behaviors such as differentiation, viability, and proliferation. Apart from being able to trigger these effects, mechanical stiffness tuning is a very convenient approach that could be implemented readily into smart scaffold designs. In this study, fibrinogen-modified poly(ethylene glycol-diacrylate (PEG-DA based hydrogels with tunable mechanical properties were synthesized and applied to control the spheroid formation and liver-like function of encapsulated Huh7.5 cells in an engineered, three-dimensional liver tissue model. By controlling hydrogel stiffness (0.1-6 kPa as a cue for mechanotransduction representing different stiffness of a normal liver and a diseased cirrhotic liver, spheroids ranging from 50 to 200 μm were formed over a three week time-span. Hydrogels with better compliance (i.e. lower stiffness promoted formation of larger spheroids. The highest rates of cell proliferation, albumin secretion, and CYP450 expression were all observed for spheroids in less stiff hydrogels like a normal liver in a healthy state. We also identified that the hydrogel modification by incorporation of PEGylated-fibrinogen within the hydrogel matrix enhanced cell survival and functionality possibly owing to more binding of autocrine fibronectin. Taken together, our findings establish guidelines to control the formation of Huh7.5 cell spheroids in modified PEGDA based hydrogels. These spheroids may serve as models for applications such as screening of pharmacological drug candidates.

Effect of formulation of alginate beads on their mechanical behavior and stiffness

Institute of Scientific and Technical Information of China (English)

Eng-Seng Chan; Tek-Kaun Lim; Wan-Ping Voo; Ravindra Pogaku; Beng Ti Tey; Zhibing Zhang

2011-01-01

The aim of this work was to determine the effect of formulation of alginate beads on their mechanical behavior and stiffness when compressed at high speed. The alginate beads were formulated using different types and concentrations of alginate and gelling cations and were produced using an extrusiondripping method. Single wet beads were compressed at a speed of 40 mm/min, and their elastic limits were investigated, and the corresponding force versus displacement data were obtained. The Young's moduli of the beads were determined from the force versus displacement data using the Hertz's contact mechanics theory. The alginate beads were found to exhibit plastic behavior when they were compressed beyond 50％ with the exception of copper-alginate beads for which yield occured at lower deformation.Alginate beads made of higher guluronic acid contents and gelling cations of higher chemical affinity were found to have greater stiffness. Increasing the concentration of alginate and gelling ions also generated a similar effect. At such a compression speed, the values of Young's modulus of the beads were found to be in the range between 250 and 900 kPa depending on the bead formulation.

Accuracy and reproducibility of bending stiffness measurements by mechanical response tissue analysis in artificial human ulnas.

Science.gov (United States)

Arnold, Patricia A; Ellerbrock, Emily R; Bowman, Lyn; Loucks, Anne B

2014-11-07

Osteoporosis is characterized by reduced bone strength, but no FDA-approved medical device measures bone strength. Bone strength is strongly associated with bone stiffness, but no FDA-approved medical device measures bone stiffness either. Mechanical Response Tissue Analysis (MRTA) is a non-significant risk, non-invasive, radiation-free, vibration analysis technique for making immediate, direct functional measurements of the bending stiffness of long bones in humans in vivo. MRTA has been used for research purposes for more than 20 years, but little has been published about its accuracy. To begin to investigate its accuracy, we compared MRTA measurements of bending stiffness in 39 artificial human ulna bones to measurements made by Quasistatic Mechanical Testing (QMT). In the process, we also quantified the reproducibility (i.e., precision and repeatability) of both methods. MRTA precision (1.0±1.0%) and repeatability (3.1 ± 3.1%) were not as high as those of QMT (0.2 ± 0.2% and 1.3+1.7%, respectively; both pstiffness was indistinguishable from the identity line (p=0.44) and paired measurements by the two methods agreed within a 95% confidence interval of ± 5%. If such accuracy can be achieved on real human ulnas in situ, and if the ulna is representative of the appendicular skeleton, MRTA may prove clinically useful. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stiff mutant genes of Phycomyces target turgor pressure and wall mechanical properties to regulate elongation growth rate

Directory of Open Access Journals (Sweden)

Joseph K. E. Ortega

2012-05-01

Full Text Available Regulation of cell growth is paramount to all living organisms. In plants, algae and fungi, regulation of expansive growth of cells is required for development and morphogenesis. Also, many sensory responses of stage IVb sporangiophores of Phycomyces blakesleeanus are produced by regulating elongation growth rate (growth responses and differential elongation growth rate (tropic responses. Stiff mutant sporangiophores exhibit diminished tropic responses and are found to be defective in at least four genes; madD, madE, madF and madG. Prior experimental research suggests that the defective genes affect growth regulation, but this was not verified. All the growth of the single-celled stalk of the stage IVb sporangiophore occurs in a short region termed the growth zone. Prior experimental and theoretical research indicates that elongation growth rate of the stage IVb sporangiophore can be regulated by controlling the cell wall mechanical properties within the growth zone and the magnitude of the turgor pressure. A quantitative biophysical model for elongation growth rate is required to elucidate the relationship between wall mechanical properties and turgor pressure during growth regulation. In this study, it is hypothesized that the mechanical properties of the wall within the growth zone of stiff mutant sporangiophores are different compared to wild type. A biophysical equation for elongation growth rate is derived for fungal and plant cells with a growth zone. Two strains of stiff mutants are studied, C149 madD120 (- and C216 geo- (-. Experimental results demonstrate that turgor pressure is larger but irreversible deformation rates of the wall within the growth zone and growth zone length are smaller for stiff mutant sporangiophores compared to wild type. These findings explain the diminished tropic responses of the stiff mutant sporangiophores and suggest that the defective genes affect the amount of wall-building material delivered to the inner

Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

Directory of Open Access Journals (Sweden)

Takaoki Saneyasu

2016-01-01

Full Text Available Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis.

Atomic Force Microscopy Study on the Stiffness of Nanosized Liposomes Containing Charged Lipids.

Science.gov (United States)

Takechi-Haraya, Yuki; Goda, Yukihiro; Sakai-Kato, Kumiko

2018-06-18

It has recently been recognized that the mechanical properties of lipid nanoparticles play an important role during in vitro and in vivo behaviors such as cellular uptake, blood circulation, and biodistribution. However, there have been no quantitative investigations of the effect of commonly used charged lipids on the stiffness of nanosized liposomes. In this study, by means of atomic force microscopy (AFM), we quantified the stiffness of nanosized liposomes composed of neutrally charged lipids combined with positively or negatively charged lipids while simultaneously imaging the liposomes in aqueous medium. Our results showed that charged lipids, whether negatively or positively charged, have the effect of reducing the stiffness of nanosized liposomes, independently of the saturation degree of the lipid acyl chains; the measured stiffness values of liposomes containing charged lipids are 30-60% lower than those of their neutral counterpart liposomes. In addition, we demonstrated that the Laurdan generalized polarization values, which are related to the hydration degree of the liposomal membrane interface and often used as a qualitative indicator of liposomal membrane stiffness, do not directly correlate with the physical stiffness values of the liposomes prepared in this study. However, our results indicate that direct quantitative AFM measurement is a valuable method to gain molecular-scale information about how the hydration degree of liposomal interfaces reflects (or does not reflect) liposome stiffness as a macroscopic property. Our AFM method will contribute to the quantitative characterization of the nano-bio interaction of nanoparticles and to the optimization of the lipid composition of liposomes for clinical use.

Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

Science.gov (United States)

Stampfl, J.; Pettermann, H. E.; Liska, R.

Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

Molecular and cellular mechanisms of cadmium carcinogenesis

International Nuclear Information System (INIS)

Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

2003-01-01

Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

Lower Body Stiffness Modulation Strategies in Well Trained Female Athletes.

Science.gov (United States)

Millett, Emma L; Moresi, Mark P; Watsford, Mark L; Taylor, Paul G; Greene, David A

2016-10-01

Millett, EL, Moresi, MP, Watsford, ML, Taylor, PG, and Greene, DA. Lower body stiffness modulation strategies in well trained female athletes. J Strength Cond Res 30(10): 2845-2856, 2016-Lower extremity stiffness quantifies the relationship between the amount of leg compression and the external load to which the limb are subjected. This study aimed to assess differences in leg and joint stiffness and the subsequent kinematic and kinetic control mechanisms between athletes from various training backgrounds. Forty-seven female participants (20 nationally identified netballers, 13 high level endurance athletes and 14 age and gender matched controls) completed a maximal unilateral countermovement jump, drop jump and horizontal jump to assess stiffness. Leg stiffness, joint stiffness and associated mechanical parameters were assessed with a 10 camera motion analysis system and force plate. No significant differences were evident for leg stiffness measures between athletic groups for any of the tasks (p = 0.321-0.849). However, differences in joint stiffness and its contribution to leg stiffness, jump performance outcome measures and stiffness control mechanisms were evident between all groups. Practitioners should consider the appropriateness of the task utilised in leg stiffness screening. Inclusion of mechanistic and/or more sports specific tasks may be more appropriate for athletic groups.

Frequency-dependent micromechanics of cellularized biopolymer networks

Science.gov (United States)

Jones, Chris; Kim, Jihan; McIntyre, David; Sun, Bo

Mechanical interactions between cells and the extracellular matrix (ECM) influence many cellular behaviors such as growth, differentiation, and migration. These are dynamic processes in which the cells actively remodel the ECM. Reconstituted collagen gel is a common model ECM for studying cell-ECM interactions in vitro because collagen is the most abundant component of mammalian ECM and gives the ECM its material stiffness. We embed micron-sized particles in collagen and use holographic optical tweezers to apply forces to the particles in multiple directions and over a range of frequencies up to 10 Hz. We calculate the local compliance and show that it is dependent on both the direction and frequency of the applied force. Performing the same measurement on many particles allows us to characterize the spatial inhomogeneity of the mechanical properties and shows that the compliance decreases at higher frequencies. Performing these measurements on cell-populated collagen gels shows that cellular remodeling of the ECM changes the mechanical properties of the collagen and we investigate whether this change is dependent on the local strain and distance from nearby cells.

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

Science.gov (United States)

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

A numerical investigation into the influence of the properties of cobalt chrome cellular structures on the load transfer to the periprosthetic femur following total hip arthroplasty.

Science.gov (United States)

Hazlehurst, Kevin Brian; Wang, Chang Jiang; Stanford, Mark

2014-04-01

Stress shielding of the periprosthetic femur following total hip arthroplasty is a problem that can promote the premature loosening of femoral stems. In order to reduce the need for revision surgery it is thought that more flexible implant designs need to be considered. In this work, the mechanical properties of laser melted square pore cobalt chrome molybdenum cellular structures have been incorporated into the design of a traditional monoblock femoral stem. The influence of incorporating the properties of cellular structures on the load transfer to the periprosthetic femur was investigated using a three dimensional finite element model. Eleven different stiffness configurations were investigated by using fully porous and functionally graded approaches. This investigation confirms that the periprosthetic stress values depend on the stiffness configuration of the stem. The numerical results showed that stress shielding is reduced in the periprosthetic Gruen zones when the mechanical properties of cobalt chrome molybdenum cellular structures are used. This work identifies that monoblock femoral stems manufactured using a laser melting process, which are designed for reduced stiffness, have the potential to contribute towards reducing stress shielding. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

The endogenous fluorescence of fibroblast in collagen gels as indicator of stiffness of the extracellular matrix

Science.gov (United States)

Padilla-Martinez, J. P.; Ortega-Martinez, A.; Franco, W.

2016-03-01

The stiffness or rigidity of the extracellular matrix (ECM) regulates cell response. Established mechanical tests to measure stiffness, such as indentation and tensile tests, are invasive and destructive to the sample. Endogenous or native molecules to cells and ECM components, like tryptophan and cross-links of collagen, display fluorescence upon irradiation with ultraviolet light. Most likely, the concentration of these endogenous fluorophores changes as the stiffness of the ECM changes. In this work we investigate the endogenous fluorescence of collagen gels containing fibroblasts as a non-invasive non-destructive method to measure stiffness of the ECM. Human fibroblast cells were cultured in three-dimensional gels of type I collagen (50,000 cells/ml). This construct is a simple model of tissue contraction. During contraction, changes in the excitation-emission matrix (a fluorescence map in the 240-520/290-530 nm range) of constructs were measured with a spectrofluoremeter, and changes in stiffness were measured with a standard indentation test over 16 days. Results show that a progressive increase in fluorescence of the 290/340 nm excitation-emission pair correlates with a progressive increase in stiffness (r=0.9, α=0.5). The fluorescence of this excitation-emission pair is ascribed to tryptophan and variations in the fluorescence of this pair correlate with cellular proliferation. In this tissue model, the endogenous functional fluorescence of proliferating fibroblast cells is a biomechanical marker of stiffness of the ECM.

Analytical study of a quasi-zero stiffness coupling using a torsion magnetic spring with negative stiffness

Science.gov (United States)

Zheng, Yisheng; Zhang, Xinong; Luo, Yajun; Zhang, Yahong; Xie, Shilin

2018-02-01

By now, many translation quasi-zero stiffness (QZS) mechanisms have been proposed to overcome the restriction between the isolation frequency range and the load bearing capacity of linear isolators. The couplings of rotor systems undertake the functions of transmitting static driving torque and isolating disturbing torque simultaneously, which creates the demand of torsion QZS mechanisms. Hence a QZS coupling is presented in this paper, where a torsion magnetic spring (TMS) composed of two coaxial ring magnet arrangements in repulsive configuration is employed to produce negative torsion stiffness to counteract the positive stiffness of a rubber spring. In this paper, the expressions of magnetic torque and stiffness are given firstly and verified by finite element simulations; and the effect of geometric parameters of the TMS on its stiffness characteristic is analyzed in detail, which contributes to the optimal design of the TMS. Then dynamic analysis of the QZS coupling is performed and the analytical expression of the torque transmissibility is achieved based on the Harmonic Balance Method. Finally, simulation of the torque transmissibility is carried out to reveal how geometric parameters of the TMS affect the isolation performance.

Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?

Science.gov (United States)

Gao, Yuan Z.; Saphirstein, Robert J.; Yamin, Rina; Suki, Bela

2014-01-01

Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small-molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of NG-nitro-l-arginine methyl ester (l-NAME) to remove interference of endothelial nitric oxide, increases stiffness by 90–200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which 1) VSMCs are a surprisingly large component of aortic stiffness at physiological lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors. PMID:25128168

The mechanical memory of lung myofibroblasts.

Science.gov (United States)

Balestrini, Jenna L; Chaudhry, Sidharth; Sarrazy, Vincent; Koehler, Anne; Hinz, Boris

2012-04-01

Fibroblasts differentiate into the highly synthetic and contractile myofibroblast phenotype when exposed to substrates with an elastic modulus corresponding to pathologically stiff fibrotic tissue. Cellular responses to changes in substrate stiffness are typically analyzed after hours or days, which does not enable the monitoring of myofibroblast persistence, a hallmark of fibrosis. To determine long-lasting effects on the fibrotic behavior of lung fibroblasts, we followed a novel approach of explanting and repeatedly passaging fibroblasts on silicone substrates with stiffness representing various states of lung health. Fibrotic activity was determined by assaying for myofibroblast proliferation, cell contractility, expression of α-smooth muscle actin, extracellular matrix and active TGFβ1. As predicted, myofibroblast activity was low on healthy soft substrates and increased with increasing substrate stiffness. However, explanting and mechanically priming lung fibroblasts for 3 weeks on pathologically stiff substrates resulted in sustained myofibroblast activity even after the cells were returned to healthy soft cultures for 2 weeks. Such primed cells retained higher fibrotic activity than cells that had been exclusively cultured on soft substrates, and were not statistically different from cells continuously passaged on stiff surfaces. Inversely, priming lung fibroblasts for 3 weeks on soft substrates partially protected from myofibroblast activation after the shift to stiff substrates. Hence, mechano-sensed information relating to physical conditions of the local cellular environment could permanently induce fibrotic behavior of lung fibroblasts. This priming effect has important implications for the progression and persistence of aggressive fibrotic diseases such as idiopathic pulmonary fibrosis. This journal is © The Royal Society of Chemistry 2012

Mechanically stiff, electrically conductive composites of polymers and carbon nanotubes

Science.gov (United States)

Worsley, Marcus A.; Kucheyev, Sergei O.; Baumann, Theodore F.; Kuntz, Joshua D.; Satcher, Jr., Joe H.; Hamza, Alex V.

2015-07-21

Using SWNT-CA as scaffolds to fabricate stiff, highly conductive polymer (PDMS) composites. The SWNT-CA is immersing in a polymer resin to produce a SWNT-CA infiltrated with a polymer resin. The SWNT-CA infiltrated with a polymer resin is cured to produce the stiff and electrically conductive composite of carbon nanotube aerogel and polymer.

Mechanically stiff, electrically conductive composites of polymers and carbon nanotubes

Energy Technology Data Exchange (ETDEWEB)

Worsley, Marcus A.; Kucheyev, Sergei O.; Baumann, Theodore F.; Kuntz, Joshua D.; Satcher, Jr., Joe H.; Hamza, Alex V.

2017-10-17

Using SWNT-CA as scaffolds to fabricate stiff, highly conductive polymer (PDMS) composites. The SWNT-CA is immersing in a polymer resin to produce a SWNT-CA infiltrated with a polymer resin. The SWNT-CA infiltrated with a polymer resin is cured to produce the stiff and electrically conductive composite of carbon nanotube aerogel and polymer.

A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells.

Science.gov (United States)

Shenoy, Vivek B; Wang, Hailong; Wang, Xiao

2016-02-06

We propose a chemo-mechanical model based on stress-dependent recruitment of myosin motors to describe how the contractility, polarization and strain in cells vary with the stiffness of their surroundings and their shape. A contractility tensor, which depends on the distribution of myosin motors, is introduced to describe the chemical free energy of the cell due to myosin recruitment. We explicitly include the contributions to the free energy that arise from mechanosensitive signalling pathways (such as the SFX, Rho-Rock and MLCK pathways) through chemo-mechanical coupling parameters. Taking the variations of the total free energy, which consists of the chemical and mechanical components, in accordance with the second law of thermodynamics provides equations for the temporal evolution of the active stress and the contractility tensor. Following this approach, we are able to recover the well-known Hill relation for active stresses, based on the fundamental principles of irreversible thermodynamics rather than phenomenology. We have numerically implemented our free energy-based approach to model spatial distribution of strain and contractility in (i) cells supported by flexible microposts, (ii) cells on two-dimensional substrates, and (iii) cells in three-dimensional matrices. We demonstrate how the polarization of the cells and the orientation of stress fibres can be deduced from the eigenvalues and eigenvectors of the contractility tensor. Our calculations suggest that the chemical free energy of the cell decreases with the stiffness of the extracellular environment as the cytoskeleton polarizes in response to stress-dependent recruitment of molecular motors. The mechanical energy, which includes the strain energy and motor potential energy, however, increases with stiffness, but the overall energy is lower for cells in stiffer environments. This provides a thermodynamic basis for durotaxis, whereby cells preferentially migrate towards stiffer regions of the

Stiffness Evaluation of High Temperature Superconductor Bearing Stiffness for 10 kWh Superconductor Flywheel Energy Storage System

International Nuclear Information System (INIS)

Park, B. J.; Jung, S. Y.; Lee, J. P.; Park, B. C.; Kim, C. H.; Han, S. C.; Du, S. G.; Han, Y. H.; Sung, T. H.

2009-01-01

A superconductor flywheel energy storage(SFES) system is mainly act an electro-mechanical battery which transfers mechanical energy into electrical form and vice versa. SFES system consists of a pair of non-contacting High Temperature Superconductor (HTS) bearings with a very low frictional loss. But it is essential to design an efficient HTS bearing considering with rotor dynamic properties through correct calculation of stiffness in order to support a huge composite flywheel rotor with high energy storage density. Static properties of HTS bearings provide data to solve problems which may occur easily in a running system. Since stiffness to counter vibration is the main parameter in designing an HTS bearing system, we investigate HTS bearing magnetic force through static properties between the Permanent Magnet(PM) and HTS. We measured axial / radial stiffness and found bearing stiffness can be easily changed by activated vibration direction between PM and HTS bulk. These results are used to determine the optimal design for a 10 kWh SFES.

Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

Science.gov (United States)

Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

2016-08-01

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

Biomechanical constraints on the feedforward regulation of endpoint stiffness.

Science.gov (United States)

Hu, Xiao; Murray, Wendy M; Perreault, Eric J

2012-10-01

Although many daily tasks tend to destabilize arm posture, it is still possible to have stable interactions with the environment by regulating the multijoint mechanics of the arm in a task-appropriate manner. For postural tasks, this regulation involves the appropriate control of endpoint stiffness, which represents the stiffness of the arm at the hand. Although experimental studies have been used to evaluate endpoint stiffness control, including the orientation of maximal stiffness, the underlying neural strategies remain unknown. Specifically, the relative importance of feedforward and feedback mechanisms has yet to be determined due to the difficulty separately identifying the contributions of these mechanisms in human experiments. This study used a previously validated three-dimensional musculoskeletal model of the arm to quantify the degree to which the orientation of maximal endpoint stiffness could be changed using only steady-state muscle activations, used to represent feedforward motor commands. Our hypothesis was that the feedforward control of endpoint stiffness orientation would be significantly constrained by the biomechanical properties of the musculoskeletal system. Our results supported this hypothesis, demonstrating substantial biomechanical constraints on the ability to regulate endpoint stiffness throughout the workspace. The ability to regulate stiffness orientation was further constrained by additional task requirements, such as the need to support the arm against gravity or exert forces on the environment. Together, these results bound the degree to which slowly varying feedforward motor commands can be used to regulate the orientation of maximum arm stiffness and provide a context for better understanding conditions in which feedback control may be needed.

Symposium on molecular and cellular mechanisms of mutagenesis

International Nuclear Information System (INIS)

1981-01-01

These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Directory of Open Access Journals (Sweden)

Jinpeng Qi

Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Science.gov (United States)

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

A mechanism to compensate undesired stiffness in joints of prosthetic hands

NARCIS (Netherlands)

Smit, G.; Plettenbrug, D.H.; Van der Helm, F.C.T.

2014-01-01

Background: Cosmetic gloves that cover a prosthetic hand have a parasitic positive stiffness that counteracts the flexion of a finger joint. Objectives: Reducing the required input torque to move a finger of a prosthetic hand by compensating the parasitic stiffness of the cosmetic glove. Study

Symposium on molecular and cellular mechanisms of mutagenesis

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents. (ERB)

Subspace methods for identification of human ankle joint stiffness.

Science.gov (United States)

Zhao, Y; Westwick, D T; Kearney, R E

2011-11-01

Joint stiffness, the dynamic relationship between the angular position of a joint and the torque acting about it, describes the dynamic, mechanical behavior of a joint during posture and movement. Joint stiffness arises from both intrinsic and reflex mechanisms, but the torques due to these mechanisms cannot be measured separately experimentally, since they appear and change together. Therefore, the direct estimation of the intrinsic and reflex stiffnesses is difficult. In this paper, we present a new, two-step procedure to estimate the intrinsic and reflex components of ankle stiffness. In the first step, a discrete-time, subspace-based method is used to estimate a state-space model for overall stiffness from the measured overall torque and then predict the intrinsic and reflex torques. In the second step, continuous-time models for the intrinsic and reflex stiffnesses are estimated from the predicted intrinsic and reflex torques. Simulations and experimental results demonstrate that the algorithm estimates the intrinsic and reflex stiffnesses accurately. The new subspace-based algorithm has three advantages over previous algorithms: 1) It does not require iteration, and therefore, will always converge to an optimal solution; 2) it provides better estimates for data with high noise or short sample lengths; and 3) it provides much more accurate results for data acquired under the closed-loop conditions, that prevail when subjects interact with compliant loads.

Cellular Mechanisms of Somatic Stem Cell Aging

Science.gov (United States)

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

Cellular automata and statistical mechanical models

International Nuclear Information System (INIS)

Rujan, P.

1987-01-01

The authors elaborate on the analogy between the transfer matrix of usual lattice models and the master equation describing the time development of cellular automata. Transient and stationary properties of probabilistic automata are linked to surface and bulk properties, respectively, of restricted statistical mechanical systems. It is demonstrated that methods of statistical physics can be successfully used to describe the dynamic and the stationary behavior of such automata. Some exact results are derived, including duality transformations, exact mappings, disorder, and linear solutions. Many examples are worked out in detail to demonstrate how to use statistical physics in order to construct cellular automata with desired properties. This approach is considered to be a first step toward the design of fully parallel, probabilistic systems whose computational abilities rely on the cooperative behavior of their components

Quasi-stationary mechanics of elastic continua with bending stiffness wrapping on a pulley system

Science.gov (United States)

Kaczmarczyk, S.; Mirhadizadeh, S.

2016-05-01

In many engineering applications elastic continua such as ropes and belts often are subject to bending when they pass over pulleys / sheaves. In this paper the quasi-stationary mechanics of a cable-pulley system is studied. The cable is modelled as a moving Euler- Bernoulli beam. The distribution of tension is non-uniform along its span and due to the bending stiffness the contact points at the pulley-beam boundaries are not unknown. The system is described by a set of nonlinear ordinary differential equations with undetermined boundary conditions. The resulting nonlinear Boundary Value Problem (BVP) with unknown boundaries is solved by converting the problem into the ‘standard’ form defined over a fixed interval. Numerical results obtained for a range of typical configurations with relevant boundary conditions applied demonstrate that due to the effects of bending stiffness the angels of wrap are reduced and the span tensions are increased.

A lightweight, biological structure with tailored stiffness: The feather vane.

Science.gov (United States)

Sullivan, Tarah N; Pissarenko, Andreï; Herrera, Steven A; Kisailus, David; Lubarda, Vlado A; Meyers, Marc A

2016-09-01

The flying feathers of birds are keratinous appendages designed for maximum performance with a minimum weight penalty. Thus, their design contains ingenious combinations of components that optimize lift, stiffness, aerodynamics, and damage resistance. This design involves two main parts: a central shaft that prescribes stiffness and lateral vanes which allows for the capture of air. Within the feather vane, barbs branch from the shaft and barbules branch from barbs, forming a flat surface which ensures lift. Microhooks at the end of barbules hold barbs tightly together, providing the close-knit, unified structure of the feather vane and enabling a repair of the structure through the reattachment of un-hooked junctions. Both the shaft and barbs are lightweight biological structures constructed of keratin using the common motif of a solid shell and cellular interior. The cellular core increases the resistance to buckling with little added weight. Here we analyze the detailed structure of the feather barb and, for the first time, explain its flexural stiffness in terms of the mechanics of asymmetric foam-filled beams subjected to bending. The results are correlated and validated with finite element modeling. We compare the flexure of single barbs as well as arrays of barbs and find that the interlocking adherence of barbs to one another enables a more robust structure due to minimized barb rotation during deflection. Thus, the flexure behavior of the feather vane can be tailored by the adhesive hooking between barbs, creating a system that mitigates damage. A simplified three-dimensional physical model for this interlocking mechanism is constructed by additive manufacturing. The exceptional architecture of the feather vane will motivate the design of bioinspired structures with tailored and unique properties ranging from adhesives to aerospace materials. Despite its importance to bird flight, literature characterizing the feather vane is extremely limited. The feather

Relationship between Static Stiffness and Modal Stiffness of Structures

Directory of Open Access Journals (Sweden)

Tianjian Ji Tianjian Ji

2010-02-01

Full Text Available This paper derives the relationship between the static stiffness and modal stiffness of a structure. The static stiffness and modal stiffness are two important concepts in both structural statics and dynamics. Although both stiffnesses indicate the capacity of the structure to resist deformation, they are obtained using different methods. The former is calculated by solving the equations of equilibrium and the latter can be obtained by solving an eigenvalue problem. A mathematical relationship between the two stiffnesses was derived based on the definitions of two stiffnesses. This relationship was applicable to a linear system and the derivation of relationships does not reveal any other limitations. Verification of the relationship was given by using several examples. The relationship between the two stiffnesses demonstrated that the modal stiffness of the fundamental mode was always larger than the static stiffness of a structure if the critical point and the maximum mode value are at the same node, i.e. for simply supported beam and seven storeys building are 1.5% and 15% respectively. The relationship could be applied into real structures, where the greater the number of modes being considered, the smaller the difference between the modal stiffness and the static stiffness of a structure.

Stiffness of RBC optical confinement affected by optical clearing

Science.gov (United States)

Grishin, Oleg V.; Fedosov, Ivan V.; Tuchin, Valery V.

2017-03-01

In vivo optical trapping is a novel applied direction of an optical manipulation, which enables one to noninvasive measurement of mechanical properties of cells and tissues in living animals directly. But an application area of this direction is limited because strong scattering of many biological tissues. An optical clearing enables one to decrease the scattering and therefore increase a depth of light penetration, decrease a distortion of light beam, improve a resolution in imaging applications. Now novel methods had appeared for a measurement an optical clearing degree at a cellular level. But these methods aren't applicable in vivo. In this paper we present novel measurement method of estimate of the optical clearing, which are based on a measurement of optical trap stiffness. Our method may be applicable in vivo.

Dynamics and mechanisms of quantum dot nanoparticle cellular uptake

Directory of Open Access Journals (Sweden)

Telford William G

2010-06-01

Full Text Available Abstract Background The rapid growth of the nanotechnology industry and the wide application of various nanomaterials have raised concerns over their impact on the environment and human health. Yet little is known about the mechanism of cellular uptake and cytotoxicity of nanoparticles. An array of nanomaterials has recently been introduced into cancer research promising for remarkable improvements in diagnosis and treatment of the disease. Among them, quantum dots (QDs distinguish themselves in offering many intrinsic photophysical properties that are desirable for targeted imaging and drug delivery. Results We explored the kinetics and mechanism of cellular uptake of QDs with different surface coatings in two human mammary cells. Using fluorescence microscopy and laser scanning cytometry (LSC, we found that both MCF-7 and MCF-10A cells internalized large amount of QD655-COOH, but the percentage of endocytosing cells is slightly higher in MCF-7 cell line than in MCF-10A cell line. Live cell fluorescent imaging showed that QD cellular uptake increases with time over 40 h of incubation. Staining cells with dyes specific to various intracellular organelles indicated that QDs were localized in lysosomes. Transmission electron microscopy (TEM images suggested a potential pathway for QD cellular uptake mechanism involving three major stages: endocytosis, sequestration in early endosomes, and translocation to later endosomes or lysosomes. No cytotoxicity was observed in cells incubated with 0.8 nM of QDs for a period of 72 h. Conclusions The findings presented here provide information on the mechanism of QD endocytosis that could be exploited to reduce non-specific targeting, thereby improving specific targeting of QDs in cancer diagnosis and treatment applications. These findings are also important in understanding the cytotoxicity of nanomaterials and in emphasizing the importance of strict environmental control of nanoparticles.

A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

Science.gov (United States)

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

Design and implementation of a novel mechanical testing system for cellular solids.

Science.gov (United States)

Nazarian, Ara; Stauber, Martin; Müller, Ralph

2005-05-01

Cellular solids constitute an important class of engineering materials encompassing both man-made and natural constructs. Materials such as wood, cork, coral, and cancellous bone are examples of cellular solids. The structural analysis of cellular solid failure has been limited to 2D sections to illustrate global fracture patterns. Due to the inherent destructiveness of 2D methods, dynamic assessment of fracture progression has not been possible. Image-guided failure assessment (IGFA), a noninvasive technique to analyze 3D progressive bone failure, has been developed utilizing stepwise microcompression in combination with time-lapsed microcomputed tomographic imaging (microCT). This method allows for the assessment of fracture progression in the plastic region, where much of the structural deformation/energy absorption is encountered in a cellular solid. Therefore, the goal of this project was to design and fabricate a novel micromechanical testing system to validate the effectiveness of the stepwise IGFA technique compared to classical continuous mechanical testing, using a variety of engineered and natural cellular solids. In our analysis, we found stepwise compression to be a valid approach for IGFA with high precision and accuracy comparable to classical continuous testing. Therefore, this approach complements the conventional mechanical testing methods by providing visual insight into the failure propagation mechanisms of cellular solids. (c) 2005 Wiley Periodicals, Inc.

Cellular mechanisms of nociception in the frog

Czech Academy of Sciences Publication Activity Database

Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

2002-01-01

Roč. 88, č. 4 (2002), s. 1843-1850 ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant - others:NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

Osmosensory mechanisms in cellular and systemic volume regulation

DEFF Research Database (Denmark)

Pedersen, Stine Helene Falsig; Kapus, András; Hoffmann, Else K

2011-01-01

Perturbations of cellular and systemic osmolarity severely challenge the function of all organisms and are consequently regulated very tightly. Here we outline current evidence on how cells sense volume perturbations, with particular focus on mechanisms relevant to the kidneys and to extracellular...

Elastin in large artery stiffness and hypertension

Science.gov (United States)

Wagenseil, Jessica E.; Mecham, Robert P.

2012-01-01

Large artery stiffness, as measured by pulse wave velocity (PWV), is correlated with high blood pressure and may be a causative factor in essential hypertension. The extracellular matrix components, specifically the mix of elastin and collagen in the vessel wall, determine the passive mechanical properties of the large arteries. Elastin is organized into elastic fibers in the wall during arterial development in a complex process that requires spatial and temporal coordination of numerous proteins. The elastic fibers last the lifetime of the organism, but are subject to proteolytic degradation and chemical alterations that change their mechanical properties. This review discusses how alterations in the amount, assembly, organization or chemical properties of the elastic fibers affect arterial stiffness and blood pressure. Strategies for encouraging or reversing alterations to the elastic fibers are addressed. Methods for determining the efficacy of these strategies, by measuring elastin amounts and arterial stiffness, are summarized. Therapies that have a direct effect on arterial stiffness through alterations to the elastic fibers in the wall may be an effective treatment for essential hypertension. PMID:22290157

The Variable Stiffness Actuator vsaUT-II: Mechanical Design, Modeling, and Identification

NARCIS (Netherlands)

Groothuis, Stefan; Rusticelli, Giacomo; Zucchelli, Andrea; Stramigioli, Stefano; Carloni, Raffaella

In this paper, the rotational variable stiffness actuator vsaUT-II is presented. This actuation system is characterized by the property that the apparent stiffness at the actuator output can be varied independently from its position. This behavior is realized by implementing a variable transmission

An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability.

Science.gov (United States)

Cruise, Denise R; Chagdes, James R; Liddy, Joshua J; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Raman, Arvind

2017-07-26

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Probing cellular mechanoadaptation using cell-substrate de-adhesion dynamics: experiments and model.

Science.gov (United States)

S S, Soumya; Sthanam, Lakshmi Kavitha; Padinhateeri, Ranjith; Inamdar, Mandar M; Sen, Shamik

2014-01-01

Physical properties of the extracellular matrix (ECM) are known to regulate cellular processes ranging from spreading to differentiation, with alterations in cell phenotype closely associated with changes in physical properties of cells themselves. When plated on substrates of varying stiffness, fibroblasts have been shown to exhibit stiffness matching property, wherein cell cortical stiffness increases in proportion to substrate stiffness up to 5 kPa, and subsequently saturates. Similar mechanoadaptation responses have also been observed in other cell types. Trypsin de-adhesion represents a simple experimental framework for probing the contractile mechanics of adherent cells, with de-adhesion timescales shown to scale inversely with cortical stiffness values. In this study, we combine experiments and computation in deciphering the influence of substrate properties in regulating de-adhesion dynamics of adherent cells. We first show that NIH 3T3 fibroblasts cultured on collagen-coated polyacrylamide hydrogels de-adhere faster on stiffer substrates. Using a simple computational model, we qualitatively show how substrate stiffness and cell-substrate bond breakage rate collectively influence de-adhesion timescales, and also obtain analytical expressions of de-adhesion timescales in certain regimes of the parameter space. Finally, by comparing stiffness-dependent experimental and computational de-adhesion responses, we show that faster de-adhesion on stiffer substrates arises due to force-dependent breakage of cell-matrix adhesions. In addition to illustrating the utility of employing trypsin de-adhesion as a biophysical tool for probing mechanoadaptation, our computational results highlight the collective interplay of substrate properties and bond breakage rate in setting de-adhesion timescales.

Damper modules with adapted stiffness ratio

Energy Technology Data Exchange (ETDEWEB)

Sonnenburg, R.; Stretz, A. [ZF Sachs AG, Entwicklungszentrum, Schweinfurt (Germany)

2011-07-15

A mechanism for the excitation of piston rod vibrations in automotive damper modules is discussed by a simple model. An improved nonlinear model based on elasticity effects leads to good simulation results. It is shown theoretically and experimentally that the adaptation of the stiffness of the piston rod bushing to the ''stiffness'' of the damper force characteristic can eliminate the piston rod oscillations completely. (orig.)

A multiwell platform for studying stiffness-dependent cell biology.

Science.gov (United States)

Mih, Justin D; Sharif, Asma S; Liu, Fei; Marinkovic, Aleksandar; Symer, Matthew M; Tschumperlin, Daniel J

2011-01-01

Adherent cells are typically cultured on rigid substrates that are orders of magnitude stiffer than their tissue of origin. Here, we describe a method to rapidly fabricate 96 and 384 well platforms for routine screening of cells in tissue-relevant stiffness contexts. Briefly, polyacrylamide (PA) hydrogels are cast in glass-bottom plates, functionalized with collagen, and sterilized for cell culture. The Young's modulus of each substrate can be specified from 0.3 to 55 kPa, with collagen surface density held constant over the stiffness range. Using automated fluorescence microscopy, we captured the morphological variations of 7 cell types cultured across a physiological range of stiffness within a 384 well plate. We performed assays of cell number, proliferation, and apoptosis in 96 wells and resolved distinct profiles of cell growth as a function of stiffness among primary and immortalized cell lines. We found that the stiffness-dependent growth of normal human lung fibroblasts is largely invariant with collagen density, and that differences in their accumulation are amplified by increasing serum concentration. Further, we performed a screen of 18 bioactive small molecules and identified compounds with enhanced or reduced effects on soft versus rigid substrates, including blebbistatin, which abolished the suppression of lung fibroblast growth at 1 kPa. The ability to deploy PA gels in multiwell plates for high throughput analysis of cells in tissue-relevant environments opens new opportunities for the discovery of cellular responses that operate in specific stiffness regimes.

A multiwell platform for studying stiffness-dependent cell biology.

Directory of Open Access Journals (Sweden)

Justin D Mih

Full Text Available Adherent cells are typically cultured on rigid substrates that are orders of magnitude stiffer than their tissue of origin. Here, we describe a method to rapidly fabricate 96 and 384 well platforms for routine screening of cells in tissue-relevant stiffness contexts. Briefly, polyacrylamide (PA hydrogels are cast in glass-bottom plates, functionalized with collagen, and sterilized for cell culture. The Young's modulus of each substrate can be specified from 0.3 to 55 kPa, with collagen surface density held constant over the stiffness range. Using automated fluorescence microscopy, we captured the morphological variations of 7 cell types cultured across a physiological range of stiffness within a 384 well plate. We performed assays of cell number, proliferation, and apoptosis in 96 wells and resolved distinct profiles of cell growth as a function of stiffness among primary and immortalized cell lines. We found that the stiffness-dependent growth of normal human lung fibroblasts is largely invariant with collagen density, and that differences in their accumulation are amplified by increasing serum concentration. Further, we performed a screen of 18 bioactive small molecules and identified compounds with enhanced or reduced effects on soft versus rigid substrates, including blebbistatin, which abolished the suppression of lung fibroblast growth at 1 kPa. The ability to deploy PA gels in multiwell plates for high throughput analysis of cells in tissue-relevant environments opens new opportunities for the discovery of cellular responses that operate in specific stiffness regimes.

Open-cellular copper structures fabricated by additive manufacturing using electron beam melting

International Nuclear Information System (INIS)

Ramirez, D.A.; Murr, L.E.; Li, S.J.; Tian, Y.X.; Martinez, E.; Martinez, J.L.; Machado, B.I.; Gaytan, S.M.; Medina, F.; Wicker, R.B.

2011-01-01

Highlights: → Relative stiffness versus relative density measurements for reticulated mesh and stochastic open cellular copper were shown to follow the Gibson-Ashby foam model. → Microstructures for the mesh struts and foam ligaments illustrated a propensity of copper oxide precipitates which provided structural hardness and strength. → These components, fabricated by electron beam melting, exhibit interesting prospects for specialized, complex heat-transfer devices. - Abstract: Cu reticulated mesh and stochastic open cellular foams were fabricated by additive manufacturing using electron beam melting. Fabricated densities ranged from 0.73 g/cm 3 to 6.67 g/cm 3 . The precursor Cu powder contained Cu 2 O precipitates and the fabricated components contained arrays of Cu 2 O precipitates and interconnected dislocation microstructures having average spacings of ∼2 μm, which provide hardness values ∼75% above commercial Cu products. Plots of stiffness (Young's modulus) versus density and relative stiffness versus relative density were in very close agreement with the Gibson-Ashby model for open cellular foams. These open cellular structure components exhibit considerable potential for novel, complex, multi-functional electrical and thermal management systems, especially complex, monolithic heat exchange devices.

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

Evaluating pulp stiffness from fibre bundles by ultrasound

Science.gov (United States)

Karppinen, Timo; Montonen, Risto; Määttänen, Marjo; Ekman, Axel; Myllys, Markko; Timonen, Jussi; Hæggström, Edward

2012-06-01

A non-destructive ultrasonic tester was developed to measure the stiffness of pulp bundles. The mechanical properties of pulp are important when estimating the behaviour of paper under stress. Currently available pulp tests are tedious and alter the fibres structurally and mechanically. The developed tester employs (933 ± 15) kHz tweezer-like ultrasonic transducers and time-of-flight measurement through (9.0 ± 2.5) mm long and (0.8 ± 0.1) mm thick fibre bundles kept at (19.1 ± 0.4) °C and (62 ± 1)% RH. We determined the stiffness of soft wood pulps produced by three kraft pulping modifications: standard kraft pulp, (5.2 ± 0.4) GPa, prehydrolysis kraft pulp, (4.3 ± 0.4) GPa, and alkali extracted prehydrolysis kraft pulp, (3.3 ± 0.4) GPa. Prehydrolysis and alkali extraction processes mainly lowered the hemicellulose content of the pulps, which essentially decreased the fibre-wall stiffness hence impairing the stiffness of the fibre networks. Our results indicate that the method allows ranking of pulps according to their stiffness determined from bundle-like samples taken at an early phase of the papermaking process.

Association of Gastrocnemius Muscle Stiffness With Passive Ankle Joint Stiffness and Sex-Related Difference in the Joint Stiffness.

Science.gov (United States)

Chino, Kintaro; Takashi, Hideyuki

2017-11-15

Passive ankle joint stiffness is affected by all structures located within and over the joint, and is greater in men than in women. Localized muscle stiffness can be assessed by ultrasound shear wave elastography, and muscle architecture such as fascicle length and pennation angle can be measured by B-mode ultrasonography. Thus, we assessed localized muscle stiffness of the medial gastrocnemius (MG) with consideration of individual variability in the muscle architecture, and examined the association of the muscle stiffness with passive ankle joint stiffness and the sex-related difference in the joint stiffness. Localized muscle stiffness of the MG in 16 men and 17 women was assessed at 10° and 20° plantar flexion, neutral anatomical position, 10° and 20° dorsiflexion. Fascicle length and pennation angle of the MG were measured at these joint positions. Passive ankle joint stiffness was determined by the ankle joint angle-torque relationship. Localized MG muscle stiffness was not significantly correlated with passive ankle joint stiffness, and did not show significant sex-related difference, even when considering the muscle architecture. This finding suggest that muscle stiffness of the MG would not be a prominent factor to determine passive ankle joint stiffness and the sex-related difference in the joint stiffness.

Magnetic resonance elastography of the lung parenchyma in an in situ porcine model with a noninvasive mechanical driver: correlation of shear stiffness with trans-respiratory system pressures.

Science.gov (United States)

Mariappan, Yogesh K; Kolipaka, Arunark; Manduca, Armando; Hubmayr, Rolf D; Ehman, Richard L; Araoz, Philip; McGee, Kiaran P

2012-01-01

Quantification of the mechanical properties of lung parenchyma is an active field of research due to the association of this metric with normal function, disease initiation and progression. A phase contrast MRI-based elasticity imaging technique known as magnetic resonance elastography is being investigated as a method for measuring the shear stiffness of lung parenchyma. Previous experiments performed with small animals using invasive drivers in direct contact with the lungs have indicated that the quantification of lung shear modulus with (1) H based magnetic resonance elastography is feasible. This technique has been extended to an in situ porcine model with a noninvasive mechanical driver placed on the chest wall. This approach was tested to measure the change in parenchymal stiffness as a function of airway opening pressure (P(ao) ) in 10 adult pigs. In all animals, shear stiffness was successfully quantified at four different P(ao) values. Mean (±STD error of mean) pulmonary parenchyma density corrected stiffness values were calculated to be 1.48 (±0.09), 1.68 (±0.10), 2.05 (±0.13), and 2.23 (±0.17) kPa for P(ao) values of 5, 10, 15, and 20 cm H2O, respectively. Shear stiffness increased with increasing P(ao) , in agreement with the literature. It is concluded that in an in situ porcine lung shear stiffness can be quantitated with (1) H magnetic resonance elastography using a noninvasive mechanical driver and that it is feasible to measure the change in shear stiffness due to change in P(ao) . Copyright © 2011 Wiley-Liss, Inc.

Escaping the Ashby limit for mechanical damping/stiffness trade-off using a constrained high internal friction interfacial layer.

Science.gov (United States)

Unwin, A P; Hine, P J; Ward, I M; Fujita, M; Tanaka, E; Gusev, A A

2018-02-06

The development of new materials with reduced noise and vibration levels is an active area of research due to concerns in various aspects of environmental noise pollution and its effects on health. Excessive vibrations also reduce the service live of the structures and limit the fields of their utilization. In oscillations, the viscoelastic moduli of a material are complex and it is their loss part - the product of the stiffness part and loss tangent - that is commonly viewed as a figure of merit in noise and vibration damping applications. The stiffness modulus and loss tangent are usually mutually exclusive properties so it is a technological challenge to develop materials that simultaneously combine high stiffness and high loss. Here we achieve this rare balance of properties by filling a solid polymer matrix with rigid inorganic spheres coated by a sub-micron layer of a viscoelastic material with a high level of internal friction. We demonstrate that this combination can be experimentally realised and that the analytically predicted behaviour is closely reproduced, thereby escaping the often termed 'Ashby' limit for mechanical stiffness/damping trade-off and offering a new route for manufacturing advanced composite structures with markedly reduced noise and vibration levels.

Ball Bearing Stiffnesses- A New Approach Offering Analytical Expressions

Science.gov (United States)

Guay, Pascal; Frikha, Ahmed

2015-09-01

Space mechanisms use preloaded ball bearings in order to withstand the severe vibrations during launch.The launch strength requires the calculation of the bearing stiffness, but this calculation is complex. Nowadays, there is no analytical expression that gives the stiffness of a bearing. Stiffness is computed using an iterative algorithm such as Newton-Raphson, to solve the nonlinear system of equations.This paper aims at offering a simplified analytical approach, based on the assumption that the contact angle is constant. This approach gives analytical formulas of the stiffness of preloaded ball bearing.

Contact stiffness and damping of liquid films in dynamic atomic force microscope

International Nuclear Information System (INIS)

Xu, Rong-Guang; Leng, Yongsheng

2016-01-01

The mechanical properties and dissipation behaviors of nanometers confined liquid films have been long-standing interests in surface force measurements. The correlation between the contact stiffness and damping of the nanoconfined film is still not well understood. We establish a novel computational framework through molecular dynamics (MD) simulation for the first time to study small-amplitude dynamic atomic force microscopy (dynamic AFM) in a simple nonpolar liquid. Through introducing a tip driven dynamics to mimic the mechanical oscillations of the dynamic AFM tip-cantilever assembly, we find that the contact stiffness and damping of the confined film exhibit distinct oscillations within 6-7 monolayer distances, and they are generally out-of-phase. For the solid-like film with integer monolayer thickness, further compression of the film before layering transition leads to higher stiffness and lower damping, while much lower stiffness and higher damping occur at non-integer monolayer distances. These two alternating mechanisms dominate the mechanical properties and dissipation behaviors of simple liquid films under cyclic elastic compression and inelastic squeeze-out. Our MD simulations provide a direct picture of correlations between the structural property, mechanical stiffness, and dissipation behavior of the nanoconfined film.

Contact stiffness and damping of liquid films in dynamic atomic force microscope

Energy Technology Data Exchange (ETDEWEB)

Xu, Rong-Guang; Leng, Yongsheng, E-mail: leng@gwu.edu [Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052 (United States)

2016-04-21

The mechanical properties and dissipation behaviors of nanometers confined liquid films have been long-standing interests in surface force measurements. The correlation between the contact stiffness and damping of the nanoconfined film is still not well understood. We establish a novel computational framework through molecular dynamics (MD) simulation for the first time to study small-amplitude dynamic atomic force microscopy (dynamic AFM) in a simple nonpolar liquid. Through introducing a tip driven dynamics to mimic the mechanical oscillations of the dynamic AFM tip-cantilever assembly, we find that the contact stiffness and damping of the confined film exhibit distinct oscillations within 6-7 monolayer distances, and they are generally out-of-phase. For the solid-like film with integer monolayer thickness, further compression of the film before layering transition leads to higher stiffness and lower damping, while much lower stiffness and higher damping occur at non-integer monolayer distances. These two alternating mechanisms dominate the mechanical properties and dissipation behaviors of simple liquid films under cyclic elastic compression and inelastic squeeze-out. Our MD simulations provide a direct picture of correlations between the structural property, mechanical stiffness, and dissipation behavior of the nanoconfined film.

Lamb wave characterization of the effects of long-term thermal-mechanical aging on composite stiffness

Science.gov (United States)

Seale, M. D.; Madaras, E. I.

1999-01-01

Lamb waves offer a promising method of evaluating damage in composite materials. The Lamb wave velocity is directly related to the material parameters, so an effective tool exists to monitor damage in composites by measuring the velocity of these waves. The Lamb Wave Imager (LWI) uses a pulse/receive technique that excites an antisymmetric Lamb mode and measures the time-of-flight over a wide frequency range. Given the material density and plate thickness, the bending and out-of-plane shear stiffnesses are calculated from a reconstruction of the dispersion curve. In this study, the time-of-flight as well as the elastic stiffnesses D11, D22, A44, and A55 for composite samples which have undergone combined thermal and mechanical aging are obtained. The samples examined include a baseline specimen with 0 cycles, specimens which have been aged 2350 and 3530 cycles at high strain levels, and one specimen aged 3530 cycles at low strain levels.

Cellular mechanisms within the juxtaglomerular apparatus

DEFF Research Database (Denmark)

Briggs, J P; Skøtt, O; Schnermann, J

1990-01-01

Cl concentration at the macular densa. This change also results in inhibition of secretion of renin. The macula densa has a unique location near the terminal end of the thick ascending limb, where NaCl concentration is highly flow dependent. The cellular mechanisms by which changes in tubular fluid NaCl produce...... vasoconstriction and inhibition of renin secretion are unknown, but the anatomy of the juxtaglomerular apparatus strongly suggests that such responses may be mediated by the extraglomerular mesangial cells located in the polar cushion underlying the macula densa. Recent evidence suggests that interstitial chloride...

Rigid two-axis MEMS force plate for measuring cellular traction force

International Nuclear Information System (INIS)

Takahashi, Hidetoshi; Jung, Uijin G; Shimoyama, Isao; Kan, Tetsuo; Tsukagoshi, Takuya; Matsumoto, Kiyoshi

2016-01-01

Cellular traction force is one of the important factors for understanding cell behaviors, such as spreading, migration and differentiation. Cells are known to change their behavior according to the mechanical stiffness of the environment. However, the measurement of cell traction forces on a rigid environment has remained difficult. This paper reports a micro-electromechanical systems (MEMS) force plate that provides a cellular traction force measurement on a rigid substrate. Both the high force sensitivity and high stiffness of the substrate were obtained using piezoresistive sensing elements. The proposed force plate consists of a 70 µ m  ×  15 µ m  ×  5 µ m base as the substrate for cultivating a bovine aortic smooth muscle cell, and the supporting beams with piezoresistors on the sidewall and the surface were used to measure the forces in both the horizontal and vertical directions. The spring constant and force resolution of the fabricated force plate in the horizontal direction were 0.2 N m −1 and less than 0.05 µ N, respectively. The cell traction force was measured, and the traction force increased by approximately 1 µ N over 30 min. These results demonstrate that the proposed force plate is applicable as an effective traction force measurement. (paper)

Sway‐dependent changes in standing ankle stiffness caused by muscle thixotropy

Science.gov (United States)

Sakanaka, Tania E.; Lakie, Martin

2016-01-01

Key points The passive stiffness of the calf muscles contributes to standing balance, although the properties of muscle tissue are highly labile.We investigated the effect of sway history upon intrinsic ankle stiffness and demonstrated reductions in stiffness of up to 43% during conditions of increased baseline sway.This sway dependence was most apparent when using low amplitude stiffness‐measuring perturbations, and the short‐range stiffness component was smaller during periods of high sway.These characteristics are consistent with the thixotropic properties of the calf muscles causing the observed changes in ankle stiffness.Periods of increased sway impair the passive stabilization of standing, demanding more active neural control of balance. Abstract Quiet standing is achieved through a combination of active and passive mechanisms, consisting of neural control and intrinsic mechanical stiffness of the ankle joint, respectively. The mechanical stiffness is partly determined by the calf muscles. However, the viscoelastic properties of muscle are highly labile, exhibiting a strong dependence on movement history. By measuring the effect of sway history upon ankle stiffness, the present study determines whether this lability has consequences for the passive stabilization of human standing. Ten subjects stood quietly on a rotating platform whose axis was collinear with the ankle joint. Ankle sway was increased by slowly tilting this platform in a random fashion, or decreased by fixing the body to a board. Ankle stiffness was measured by using the same platform to simultaneously apply small, brief perturbations (ankle stiffness by up to 43% compared to the body‐fixed condition. Normal quiet stance was associated with intermediate values. The effect was most apparent when using smaller perturbation amplitudes to measure stiffness (0.1 vs. 0.6 deg). Furthermore, torque responses exhibited a biphasic pattern, consisting of an initial steep rise followed by a

The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells

International Nuclear Information System (INIS)

Guo, Xinyi; Bonin, Keith; Guthold, Martin; Scarpinato, Karin

2014-01-01

Using an Atomic Force Microscope (AFM) with a 5.3 μm diameter spherical probe, we determined mechanical properties of individual human mammary epithelial cells. The cells were derived from a pair of cell lines that mimic cell progression through four phases of neoplastic transformation: normal (non-transformed), immortal, tumorigenic, and metastatic. Measurements on cells in all four phases were taken over both the cytoplasmic and nuclear regions. Moreover, the measurements were made for cells in different microenvironments as related to cell–cell contacts: isolated cells; cells residing on the periphery of a contiguous cell monolayer; and cells on the inside of a contiguous cell monolayer. By fitting the AFM force versus indentation curves to a Hertz model, we determined the pseudo-elastic Young’s modulus, E. Combining all data for the cellular subregions (over nucleus and cytoplasm) and the different cell microenvironments, we obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic phase and then stiffen somewhat in the final step to metastatic cells. We also found a distinct contrast in the influence of a cell’s microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than peripheral cells, which are stiffer than isolated cells. However, the microenvironment had a slight, opposite effect on tumorigenic and little effect on immortal and metastatic cell stiffness. Thus, the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Our results show that the mechanical properties of a cell can depend on cancer progression and microenvironment (cell–cell interactions). (paper)

The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells

Science.gov (United States)

Guo, Xinyi; Bonin, Keith; Scarpinato, Karin; Guthold, Martin

2014-10-01

Using an Atomic Force Microscope (AFM) with a 5.3 μm diameter spherical probe, we determined mechanical properties of individual human mammary epithelial cells. The cells were derived from a pair of cell lines that mimic cell progression through four phases of neoplastic transformation: normal (non-transformed), immortal, tumorigenic, and metastatic. Measurements on cells in all four phases were taken over both the cytoplasmic and nuclear regions. Moreover, the measurements were made for cells in different microenvironments as related to cell-cell contacts: isolated cells; cells residing on the periphery of a contiguous cell monolayer; and cells on the inside of a contiguous cell monolayer. By fitting the AFM force versus indentation curves to a Hertz model, we determined the pseudo-elastic Young’s modulus, E. Combining all data for the cellular subregions (over nucleus and cytoplasm) and the different cell microenvironments, we obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic phase and then stiffen somewhat in the final step to metastatic cells. We also found a distinct contrast in the influence of a cell’s microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than peripheral cells, which are stiffer than isolated cells. However, the microenvironment had a slight, opposite effect on tumorigenic and little effect on immortal and metastatic cell stiffness. Thus, the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Our results show that the mechanical properties of a cell can depend on cancer progression and microenvironment (cell-cell interactions).

A Channel Allocation Mechanism for Cellular Networks

Directory of Open Access Journals (Sweden)

Chi-Hua Chen

2017-04-01

Full Text Available In cellular networks, call blocking causes lower customer satisfaction and economic loss. Therefore, the channel allocation for call block avoidance is an important issue. This study proposes a mechanism that considers the real-time traffic information (e.g., traffic flow and vehicle speed and the user behavior (e.g., call inter-arrival time and call holding time to analyze the adaptable number of communication calls in the specific cell for channel allocation. In experiments about call block probabilities (CBP, this study simulated two cases that are the situations of the whole day and traffic accident. The simulation results show that all CBPs in the scenario of whole day are less than 21.5% by using the proposed mechanism, which is better than using the static channel allocation (SCA mechanism. Moreover, all CBPs in the scenario of traffic accidents are less than 16.5% by using the proposed mechanism, which is better than using the SCA mechanism. Therefore, the proposed mechanism can decrease the number of CBPs effectively.

Stiffness of Railway Soil-Steel Structures

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Machelski Czesław

2015-12-01

Full Text Available The considerable influence of the soil backfill properties and that of the method of compacting it on the stiffness of soil-steel structures is characteristic of the latter. The above factors (exhibiting randomness become apparent in shell deformation measurements conducted during construction and proof test loading. A definition of soil-shell structure stiffness, calculated on the basis of shell deflection under the service load, is proposed in the paper. It is demonstrated that the stiffness is the inverse of the deflection influence function used in structural mechanics. The moving load methodology is shown to be useful for testing, since it makes it possible to map the shell deflection influence line also in the case of group loads (concentrated forces, as in bridges. The analyzed cases show that the shell’s span, geometry (static scheme and the height of earth fill influence the stiffness of the structure. The soil-steel structure’s characteristic parameter in the form of stiffness k is more suitable for assessing the quality of construction works than the proposed in code geometric index ω applied to beam structures. As shown in the given examples, parameter k is more effective than stiffness parameter λ used to estimate the deformation of soil-steel structures under construction. Although the examples concern railway structures, the methodology proposed in the paper is suitable also for road bridges.

Stiffness of Railway Soil-Steel Structures

Science.gov (United States)

Machelski, Czesław

2015-12-01

The considerable influence of the soil backfill properties and that of the method of compacting it on the stiffness of soil-steel structures is characteristic of the latter. The above factors (exhibiting randomness) become apparent in shell deformation measurements conducted during construction and proof test loading. A definition of soil-shell structure stiffness, calculated on the basis of shell deflection under the service load, is proposed in the paper. It is demonstrated that the stiffness is the inverse of the deflection influence function used in structural mechanics. The moving load methodology is shown to be useful for testing, since it makes it possible to map the shell deflection influence line also in the case of group loads (concentrated forces), as in bridges. The analyzed cases show that the shell's span, geometry (static scheme) and the height of earth fill influence the stiffness of the structure. The soil-steel structure's characteristic parameter in the form of stiffness k is more suitable for assessing the quality of construction works than the proposed in code geometric index ω applied to beam structures. As shown in the given examples, parameter k is more effective than stiffness parameter λ used to estimate the deformation of soil-steel structures under construction. Although the examples concern railway structures, the methodology proposed in the paper is suitable also for road bridges.

Static stiffness modeling of a novel hybrid redundant robot machine

International Nuclear Information System (INIS)

Li Ming; Wu Huapeng; Handroos, Heikki

2011-01-01

This paper presents a modeling method to study the stiffness of a hybrid serial-parallel robot IWR (Intersector Welding Robot) for the assembly of ITER vacuum vessel. The stiffness matrix of the basic element in the robot is evaluated using matrix structural analysis (MSA); the stiffness of the parallel mechanism is investigated by taking account of the deformations of both hydraulic limbs and joints; the stiffness of the whole integrated robot is evaluated by employing the virtual joint method and the principle of virtual work. The obtained stiffness model of the hybrid robot is analytical and the deformation results of the robot workspace under certain external load are presented.

Characterization of Ti-6Al-4V open cellular foams fabricated by additive manufacturing using electron beam melting

International Nuclear Information System (INIS)

Murr, L.E.; Gaytan, S.M.; Medina, F.; Martinez, E.; Martinez, J.L.; Hernandez, D.H.; Machado, B.I.; Ramirez, D.A.; Wicker, R.B.

2010-01-01

Ti-6Al-4V open cellular foams were fabricated by additive manufacturing using electron beam melting (EBM). Foam models were developed from CT-scans of aluminum open cellular foams and embedded in CAD for EBM. These foams were fabricated with solid cell structures as well as hollow cell structures and exhibit tailorable stiffness and strength. The strength in proportion to the measured microindentation hardness is as much as 40% higher for hollow cell (wall) structures in contrast to solid, fully dense EBM fabricated components. Plots of relative stiffness versus relative density were in good agreement with the Gibson-Ashby model for open cellular foam materials. Stiffness or Young's modulus values measured using a resonant frequency-damping analysis technique were found to vary inversely with porosity especially for solid cell wall, open cellular structure foams. These foams exhibit the potential for novel biomedical, aeronautics, and automotive applications.

Plant fibre composites - porosity and stiffness

DEFF Research Database (Denmark)

Madsen, Bo; Thygesen, Anders; Lilholt, Hans

2009-01-01

Plant fibre composites contain typically a relatively large amount of porosity which influences their performance. A model, based on a modified rule of mixtures, is presented to include the influence of porosity on the composite stiffness. The model integrates the volumetric composition...... of the composites with their mechanical properties. The fibre weight fraction is used as an independent parameter to calculate the complete volumetric composition. A maximum obtainable stiffness of the composites is calculated at a certain transition fibre weight fraction, which is characterised by a best possible...... combination of high fibre volume fraction and low porosity. The model is validated with experimental data from the literature on several types of composites. A stiffness diagram is presented to demonstrate that the calculations can be used for tailoring and design of composites with a given profile...

Detection of stiff nanoparticles within cellular structures by contact resonance atomic force microscopy subsurface nanomechanical imaging.

Science.gov (United States)

Reggente, Melania; Passeri, Daniele; Angeloni, Livia; Scaramuzzo, Francesca Anna; Barteri, Mario; De Angelis, Francesca; Persiconi, Irene; De Stefano, Maria Egle; Rossi, Marco

2017-05-04

Detecting stiff nanoparticles buried in soft biological matrices by atomic force microscopy (AFM) based techniques represents a new frontier in the field of scanning probe microscopies, originally developed as surface characterization methods. Here we report the detection of stiff (magnetic) nanoparticles (NPs) internalized in cells by using contact resonance AFM (CR-AFM) employed as a potentially non-destructive subsurface characterization tool. Magnetite (Fe 3 O 4 ) NPs were internalized in microglial cells from cerebral cortices of mouse embryos of 18 days by phagocytosis. Nanomechanical imaging of cells was performed by detecting the contact resonance frequencies (CRFs) of an AFM cantilever held in contact with the sample. Agglomerates of NPs internalized in cells were visualized on the basis of the local increase in the contact stiffness with respect to the surrounding biological matrix. A second AFM-based technique for nanomechanical imaging, i.e., HarmoniX™, as well as magnetic force microscopy and light microscopy were used to confirm the CR-AFM results. Thus, CR-AFM was demonstrated as a promising technique for subsurface imaging of nanomaterials in biological samples.

Active Cellular Mechanics and its Consequences for Animal Development

Science.gov (United States)

Noll, Nicholas B.

A central goal of developmental biology is to understand how an organism shapes itself, a process referred to as morphogenesis. While the molecular components critical to determining the initial body plan have been well characterized, the control of the subsequent dynamics of cellular rearrangements which ultimately shape the organism are far less understood. A major roadblock to a more complete picture of morphogenesis is the inability to measure tissue-scale mechanics throughout development and thus answer fundamental questions: How is the mechanical state of the cell regulated by local protein expression and global pattering? In what way does stress feedback onto the larger developmental program? In this dissertation, we begin to approach these questions through the introduction and analysis of a multi-scale model of epithelial mechanics which explicitly connects cytoskeletal protein activity to tissue-level stress. In Chapter 2, we introduce the discrete Active Tension Network (ATN) model of cellular mechanics. ATNs are tissues that satisfy two primary assumptions: that the mechanical balance of cells is dominated by cortical tension and that myosin actively remodels the actin cytoskeleton in a stress-dependent manner. Remarkably, the interplay of these features allows for angle-preserving, i.e. 'isogonal', dilations or contractions of local cell geometry that do not generate stress. Asymptotically this model is stabilized provided there is mechanical feedback on expression of myosin within the cell; we take this to be a strong prediction to be tested. The ATN model exposes a fundamental connection between equilibrium cell geometry and its underlying force network. In Chapter 3, we relax the tension-net approximation and demonstrate that at equilibrium, epithelial tissues with non-uniform pressure have non-trivial geometric constraints that imply the network is described by a weighted `dual' triangulation. We show that the dual triangulation encodes all

Substrate stiffness affects skeletal myoblast differentiation in vitro

Directory of Open Access Journals (Sweden)

Sara Romanazzo, Giancarlo Forte, Mitsuhiro Ebara, Koichiro Uto, Stefania Pagliari, Takao Aoyagi, Enrico Traversa and Akiyoshi Taniguchi

2012-01-01

Full Text Available To maximize the therapeutic efficacy of cardiac muscle constructs produced by stem cells and tissue engineering protocols, suitable scaffolds should be designed to recapitulate all the characteristics of native muscle and mimic the microenvironment encountered by cells in vivo. Moreover, so not to interfere with cardiac contractility, the scaffold should be deformable enough to withstand muscle contraction. Recently, it was suggested that the mechanical properties of scaffolds can interfere with stem/progenitor cell functions, and thus careful consideration is required when choosing polymers for targeted applications. In this study, cross-linked poly-ε-caprolactone membranes having similar chemical composition and controlled stiffness in a supra-physiological range were challenged with two sources of myoblasts to evaluate the suitability of substrates with different stiffness for cell adhesion, proliferation and differentiation. Furthermore, muscle-specific and non-related feeder layers were prepared on stiff surfaces to reveal the contribution of biological and mechanical cues to skeletal muscle progenitor differentiation. We demonstrated that substrate stiffness does affect myogenic differentiation, meaning that softer substrates can promote differentiation and that a muscle-specific feeder layer can improve the degree of maturation in skeletal muscle stem cells.

The linearity of quantum mechanics from the perspective of Hamiltonian cellular automata

International Nuclear Information System (INIS)

Enrico Fermi, Università di Pisa, Largo Pontecorvo 3, I-56127 Pisa (Italy))" data-affiliation=" (Dipartimento di Fisica Enrico Fermi, Università di Pisa, Largo Pontecorvo 3, I-56127 Pisa (Italy))" >Elze, Hans-Thomas

2014-01-01

We discuss the action principle and resulting Hamiltonian equations of motion for a class of integer-valued cellular automata introduced recently [1]. Employing sampling theory, these deterministic finite-difference equations are mapped reversibly on continuum equations describing a set of bandwidth limited harmonic oscillators. They represent the Schrödinger equation. However, modifications reflecting the bandwidth limit are incorporated, i.e., the presence of a time (or length) scale. When this discreteness scale is taken to zero, the usual results are obtained. Thus, the linearity of quantum mechanics can be traced to the postulated action principle of such cellular automata and its conservation laws to discrete ones. The cellular automaton conservation laws are in one-to-one correspondence with those of the related quantum mechanical model, while admissible symmetries are not.

Stiffness compatibility of coralline hydroxyapatite bone substitute under dynamic loading

Institute of Scientific and Technical Information of China (English)

REN ChaoFeng; HOU ZhenDe; ZHAO Wei

2009-01-01

When hydroxyapatite bone substitutes are implanted in human bodies, bone tissues will grow into their porous structure, which will reinforce their strength and stiffness. The concept of mechanical com-patibility of bone substitutes implies that their mechanical properties are similar to the bone tissues around, as if they were part of the bone. The mechanical compatibility of bone substitutes includes both static and dynamic behavior, due to the mechanical properties of bone depending on the strain rate. In this study, split Hopkinson pressure bar technique (SHPB) was employed to determine the dy-namic mechanical properties of coralline hydroxyapatite, bones with and bones without organic com-ponents, and their dynamic stress-strain curves of the three materials were obtained. The mechanical effects of collagens in bone were assessed, by comparing the difference between the Young's moduli of the three materials. As the implanted bone substitute becomes a part of bone, it can be regarded as an inclusion composite. The effective modulus of the composite was also evaluated in order to estimate its mechanical compatibility on stiffness. The evaluated result shows that the suitable porosity of HA is0.8, which is in favor of both static and dynamic stiffness compatibility.

Bio-inspired composites with functionally graded platelets exhibit enhanced stiffness.

Science.gov (United States)

Tapse, Sanjay; S, Anup

2017-11-09

Unidirectional composites inspired from biological materials such as nacre, are composed of stiff platelets arranged in a staggered manner within a soft matrix. Elaborate analyses have been conducted on the aforementioned composites and they are found to have excellent mechanical properties like stiffness, strength and fracture toughness. The superior properties exhibited by these composites have been proved to be the result of its unique structure. An emerging development in the field of composite structures is Functionally Graded Composites(FGC), whose properties vary spatially and possess enhanced thermo-mechanical properties. In this paper, the platelets are functionally graded with its Young's Modulus varying parabolically along the length. Two different models - namely, Tension Shear Chain Model and Minimisation of Complementary Energy Model have been employed to obtain the stiffness of the overall composite analytically. The effect of various parameters that define the composite model such as overlapping length between any two neighbouring platelets, different gradation parameters and platelet aspect ratio on the overall mechanical properties have been studied. Composites with functionally graded platelets are found to possess enhanced stiffness (upto 14% higher) for certain values of these parameters. The obtained solutions have been validated using Finite Element Analysis. Bio-inspired composites with functionally graded platelets can be engineered for structural applications, such as in automobile, aerospace and aircraft industry, where stiffness plays a crucial role. © 2017 IOP Publishing Ltd.

Cryotherapy induces an increase in muscle stiffness.

Science.gov (United States)

Point, M; Guilhem, G; Hug, F; Nordez, A; Frey, A; Lacourpaille, L

2018-01-01

Although cold application (ie, cryotherapy) may be useful to treat sports injuries and to prevent muscle damage, it is unclear whether it has adverse effects on muscle mechanical properties. This study aimed to determine the effect of air-pulsed cryotherapy on muscle stiffness estimated using ultrasound shear wave elastography. Myoelectrical activity, ankle passive torque, shear modulus (an index of stiffness), and muscle temperature of the gastrocnemius medialis were measured before, during an air-pulsed cryotherapy (-30°C) treatment of four sets of 4 minutes with 1-minute recovery in between and during a 40 minutes postcryotherapy period. Muscle temperature significantly decreased after the second set of treatment (10 minutes: 32.3±2.5°C; Pcryotherapy induces an increase in muscle stiffness. This acute change in muscle mechanical properties may lower the amount of stretch that the muscle tissue is able to sustain without subsequent injury. This should be considered when using cryotherapy in athletic practice. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

Directory of Open Access Journals (Sweden)

Robert W Tilghman

Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

A gradual update method for simulating the steady-state solution of stiff differential equations in metabolic circuits.

Science.gov (United States)

Shiraishi, Emi; Maeda, Kazuhiro; Kurata, Hiroyuki

2009-02-01

Numerical simulation of differential equation systems plays a major role in the understanding of how metabolic network models generate particular cellular functions. On the other hand, the classical and technical problems for stiff differential equations still remain to be solved, while many elegant algorithms have been presented. To relax the stiffness problem, we propose new practical methods: the gradual update of differential-algebraic equations based on gradual application of the steady-state approximation to stiff differential equations, and the gradual update of the initial values in differential-algebraic equations. These empirical methods show a high efficiency for simulating the steady-state solutions for the stiff differential equations that existing solvers alone cannot solve. They are effective in extending the applicability of dynamic simulation to biochemical network models.

A new variable stiffness suspension system: passive case

Directory of Open Access Journals (Sweden)

O. M. Anubi

2013-02-01

Full Text Available This paper presents the design, analysis, and experimental validation of the passive case of a variable stiffness suspension system. The central concept is based on a recently designed variable stiffness mechanism. It consists of a horizontal control strut and a vertical strut. The main idea is to vary the load transfer ratio by moving the location of the point of attachment of the vertical strut to the car body. This movement is controlled passively using the horizontal strut. The system is analyzed using an L2-gain analysis based on the concept of energy dissipation. The analyses, simulation, and experimental results show that the variable stiffness suspension achieves better performance than the constant stiffness counterpart. The performance criteria used are; ride comfort, characterized by the car body acceleration, suspension deflection, and road holding, characterized by tire deflection.

Specific adaptations of neuromuscular control and knee joint stiffness following sensorimotor training.

Science.gov (United States)

Gruber, M; Bruhn, S; Gollhofer, A

2006-08-01

The aim of this study was to examine how fixations of the ankle joint during sensorimotor training (SMT) influence adaptations in mechanical stiffness and neuromuscular control of the knee joint. Sixty-three healthy subjects were randomly assigned to three training groups that differed in their degree of ankle joint fixation, which was either barefooted, with an ankle brace or with a ski boot. Mechanical knee joint stiffness and reflex control of m. vastus medialis, m. vastus lateralis, m. biceps femoris, and m. semitendinosus were tested during force controlled anterior tibial displacements. This force was applied as both a fast and a slow stimulus. After the training period the group that trained barefooted showed an increase in mechanical stiffness of the knee joint from 79 +/- 21 (Mean +/- SD) N/mm to 110 +/- 38 N/mm (p boots was able to improve knee joint stiffness from 67 +/- 26 N/mm to 96 +/- 47 N/mm (p knee joint injuries.

Nanostructured 2D cellular materials in silicon by sidewall transfer lithography NEMS

Science.gov (United States)

Syms, Richard R. A.; Liu, Dixi; Ahmad, Munir M.

2017-07-01

Sidewall transfer lithography (STL) is demonstrated as a method for parallel fabrication of 2D nanostructured cellular solids in single-crystal silicon. The linear mechanical properties of four lattices (perfect and defected diamond; singly and doubly periodic honeycomb) with low effective Young’s moduli and effective Poisson’s ratio ranging from positive to negative are modelled using analytic theory and the matrix stiffness method with an emphasis on boundary effects. The lattices are fabricated with a minimum feature size of 100 nm and an aspect ratio of 40:1 using single- and double-level STL and deep reactive ion etching of bonded silicon-on-insulator. Nanoelectromechanical systems (NEMS) containing cellular materials are used to demonstrate stretching, bending and brittle fracture. Predicted edge effects are observed, theoretical values of Poisson’s ratio are verified and failure patterns are described.

Stiffness compatibility of coralline hydroxyapatite bone substitute under dynamic loading

Institute of Scientific and Technical Information of China (English)

无

2009-01-01

When hydroxyapatite bone substitutes are implanted in human bodies,bone tissues will grow into their porous structure,which will reinforce their strength and stiffness.The concept of mechanical com-patibility of bone substitutes implies that their mechanical properties are similar to the bone tissues around,as if they were part of the bone.The mechanical compatibility of bone substitutes includes both static and dynamic behavior,due to the mechanical properties of bone depending on the strain rate.In this study,split Hopkinson pressure bar technique(SHPB) was employed to determine the dy-namic mechanical properties of coralline hydroxyapatite,bones with and bones without organic com-ponents,and their dynamic stress-strain curves of the three materials were obtained.The mechanical effects of collagens in bone were assessed,by comparing the difference between the Young’s moduli of the three materials.As the implanted bone substitute becomes a part of bone,it can be regarded as an inclusion composite.The effective modulus of the composite was also evaluated in order to estimate its mechanical compatibility on stiffness.The evaluated result shows that the suitable porosity of HA is 0.8,which is in favor of both static and dynamic stiffness compatibility.

OroSTIFF: Face-referenced measurement of perioral stiffness in health and disease.

Science.gov (United States)

Chu, Shin-Ying; Barlow, Steven M; Kieweg, Douglas; Lee, Jaehoon

2010-05-28

A new device and automated measurement technology known as OroSTIFF is described to characterize non-participatory perioral stiffness in healthy adults for eventual application to patients with orofacial movement disorders associated with neuromotor disease, traumatic injury, or congenital clefts of the upper lip. Previous studies of perioral biomechanics required head stabilization for extended periods of time during measurement, which precluded sampling patients with involuntary body/head movements (dyskinesias), or pediatric subjects. The OroSTIFF device is face-referenced and avoids the complications associated with head-restraint. Supporting data of non-participatory perioral tissue stiffness using OroSTIFF are included from 10 male and 10 female healthy subjects. The OroSTIFF device incorporates a pneumatic glass air cylinder actuator instrumented for pressure, and an integrated subminiature displacement sensor to encode lip aperture. Perioral electromyograms were simultaneously sampled to confirm passive muscle state for the superior and inferior divisions of the orbicularis oris muscles. Perioral stiffness, derived as a quotient from resultant force (DeltaF) and interangle span (DeltaX), was modeled with multilevel regression techniques. Real-time calculation of the perioral stiffness function demonstrated a significant quadratic relation between imposed interangle stretch and resultant force. This stiffness growth function also differed significantly between males and females. This study demonstrates the OroSTIFF 'proof-of-concept' for cost-effective non-invasive stimulus generation and derivation of perioral stiffness in a group of healthy unrestrained adults, and a case study to illustrate the dose-dependent effects of Levodopa on perioral stiffness in an individual with advanced Parkinson's disease who exhibited marked dyskinesia and rigidity. Copyright 2010 Elsevier Ltd. All rights reserved.

Variable stiffness corrugated composite structure with shape memory polymer for morphing skin applications

Science.gov (United States)

Gong, Xiaobo; Liu, Liwu; Scarpa, Fabrizio; Leng, Jinsong; Liu, Yanju

2017-03-01

This work presents a variable stiffness corrugated structure based on a shape memory polymer (SMP) composite with corrugated laminates as reinforcement that shows smooth aerodynamic surface, extreme mechanical anisotropy and variable stiffness for potential morphing skin applications. The smart composite corrugated structure shows a low in-plane stiffness to minimize the actuation energy, but also possess high out-of-plane stiffness to transfer the aerodynamic pressure load. The skin provides an external smooth aerodynamic surface because of the one-sided filling with the SMP. Due to variable stiffness of the shape memory polymer the morphing skin exhibits a variable stiffness with a change of temperature, which can help the skin adjust its stiffness according different service environments and also lock the temporary shape without external force. Analytical models related to the transverse and bending stiffness are derived and validated using finite element techniques. The stiffness of the morphing skin is further investigated by performing a parametric analysis against the geometry of the corrugation and various sets of SMP fillers. The theoretical and numerical models show a good agreement and demonstrate the potential of this morphing skin concept for morphing aircraft applications. We also perform a feasibility study of the use of this morphing skin in a variable camber morphing wing baseline. The results show that the morphing skin concept exhibits sufficient bending stiffness to withstand the aerodynamic load at low speed (less than 0.3 Ma), while demonstrating a large transverse stiffness variation (up to 191 times) that helps to create a maximum mechanical efficiency of the structure under varying external conditions.

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

Directory of Open Access Journals (Sweden)

Sorkin Adam M

2006-05-01

Full Text Available Abstract Background In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. Methods To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm2 for this study at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV experiments. Results Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. Conclusion The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable.

The conundrum of arterial stiffness, elevated blood pressure, and aging.

Science.gov (United States)

AlGhatrif, Majd; Lakatta, Edward G

2015-02-01

Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naïve. The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of

Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis

DEFF Research Database (Denmark)

Görtzen, Jan; Schierwagen, Robert; Bierwolf, Jeanette

2015-01-01

. This study investigated the interaction of c-SRC and RhoA under different matrix stiffness conditions. METHODS: Liver fibrosis was induced in rats using bile duct ligation (BDL), thioacetamide (TAA) or carbon tetrachloride (CCl4) models. mRNA levels of albumin, PDGF-R, RHOA, COL1A1, and αSMA were analyzed......INTRODUCTION: In liver fibrosis activation of hepatic stellate cells (HSC) comprises phenotypical change into profibrotic and myofibroplastic cells with increased contraction and secretion of extracellular matrix (ECM) proteins. The small GTPase RhoA orchestrates cytoskeleton formation, migration......, and mobility via non-receptor tyrosine-protein kinase c-SRC (cellular sarcoma) in different cells. Furthermore, RhoA and its downstream effector Rho-kinase also play a crucial role in hepatic stellate cells and hepatic fibrogenesis. Matrix stiffness promotes HSC activation via cytoskeleton modulation...

Large strain variable stiffness composites for shear deformations with applications to morphing aircraft skins

Science.gov (United States)

McKnight, G. P.; Henry, C. P.

2008-03-01

Morphing or reconfigurable structures potentially allow for previously unattainable vehicle performance by permitting several optimized structures to be achieved using a single platform. The key to enabling this technology in applications such as aircraft wings, nozzles, and control surfaces, are new engineered materials which can achieve the necessary deformations but limit losses in parasitic actuation mass and structural efficiency (stiffness/weight). These materials should exhibit precise control of deformation properties and provide high stiffness when exercised through large deformations. In this work, we build upon previous efforts in segmented reinforcement variable stiffness composites employing shape memory polymers to create prototype hybrid composite materials that combine the benefits of cellular materials with those of discontinuous reinforcement composites. These composites help overcome two key challenges for shearing wing skins: the resistance to out of plane buckling from actuation induced shear deformation, and resistance to membrane deflections resulting from distributed aerodynamic pressure loading. We designed, fabricated, and tested composite materials intended for shear deformation and address out of plane deflections in variable area wing skins. Our designs are based on the kinematic engineering of reinforcement platelets such that desired microstructural kinematics is achieved through prescribed boundary conditions. We achieve this kinematic control by etching sheets of metallic reinforcement into regular patterns of platelets and connecting ligaments. This kinematic engineering allows optimization of materials properties for a known deformation pathway. We use mechanical analysis and full field photogrammetry to relate local scale kinematics and strains to global deformations for both axial tension loading and shear loading with a pinned-diamond type fixture. The Poisson ratio of the kinematically engineered composite is ~3x higher than

Passive stiffness of rat skeletal muscle undernourished during fetal development

Directory of Open Access Journals (Sweden)

Ana Elisa Toscano

2010-01-01

Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

Cellular Mechanisms of Action of Drug Abuse on Olfactory Neurons

Directory of Open Access Journals (Sweden)

Thomas Heinbockel

2015-12-01

Full Text Available Cannabinoids (Δ9-tetrahydrocannabinol are the active ingredient of marijuana (cannabis which is the most commonly abused illicit drug in the USA. In addition to being known and used as recreational drugs, cannabinoids are produced endogenously by neurons in the brain (endocannabinoids and serve as important signaling molecules in the nervous system and the rest of the body. Cannabinoids have been implicated in bodily processes both in health and disease. Recent pharmacological and physiological experiments have described novel aspects of classic brain signaling mechanisms or revealed unknown mechanisms of cellular communication involving the endocannabinoid system. While several forms of signaling have been described for endocannabinoids, the most distinguishing feature of endocannabinoids is their ability to act as retrograde messengers in neural circuits. Neurons in the main olfactory bulb express high levels of cannabinoid receptors. Here, we describe the cellular mechanisms and function of this novel brain signaling system in regulating neural activity at synapses in olfactory circuits. Results from basic research have the potential to provide the groundwork for translating the neurobiology of drug abuse to the realm of the pharmacotherapeutic treatment of addiction, specifically marijuana substance use disorder.

Cellular Transport Mechanisms of Cytotoxic Metallodrugs: An Overview beyond Cisplatin

Directory of Open Access Journals (Sweden)

Sarah Spreckelmeyer

2014-09-01

Full Text Available The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based drugs as cancer chemotherapeutic agents have been widely studied, exact knowledge of the mechanisms governing their accumulation in cells is still lacking. However, evidence suggests active uptake and efflux mechanisms are involved; this may be involved also in other experimental metal coordination and organometallic compounds with promising antitumor activities in vitro and in vivo, such as ruthenium and gold compounds. Such knowledge would be necessary to elucidate the balance between activity and toxicity profiles of metal compounds. In this review, we present an overview of the information available on the cellular accumulation of Pt compounds from in vitro, in vivo and clinical studies, as well as a summary of reports on the possible accumulation mechanisms for different families of experimental anticancer metal complexes (e.g., Ru Au and Ir. Finally, we discuss the need for rationalization of the investigational approaches available to study metallodrug cellular transport.

Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

Science.gov (United States)

Ramos-Leví, Ana Maria; Marazuela, Mónica

2016-10-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

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Liu, Cong; Krishnan, J; Xu, Xiao Yun

2013-03-01

In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

Science.gov (United States)

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

Investigating the effect of cell substrate on cancer cell stiffness by optical tweezers.

Science.gov (United States)

Yousafzai, Muhammad Sulaiman; Coceano, Giovanna; Bonin, Serena; Niemela, Joseph; Scoles, Giacinto; Cojoc, Dan

2017-07-26

The mechanical properties of cells are influenced by their microenvironment. Here we report cell stiffness alteration by changing the cell substrate stiffness for isolated cells and cells in contact with other cells. Polydimethylsiloxane (PDMS) is used to prepare soft substrates with three different stiffness values (173, 88 and 17kPa respectively). Breast cancer cells lines, namely HBL-100, MCF-7 and MDA-MB-231 with different level of aggressiveness are cultured on these substrates and their local elasticity is investigated by vertical indentation of the cell membrane. Our preliminary results show an unforeseen behavior of the MDA-MB-231 cells. When cultured on glass substrate as isolated cells, they are less stiff than the other two types of cells, in agreement with the general statement that more aggressive and metastatic cells are softer. However, when connected to other cells the stiffness of MDA-MB-231 cells becomes similar to the other two cell lines. Moreover, the stiffness of MDA-MB-231 cells cultured on soft PDMS substrates is significantly higher than the stiffness of the other cell types, demonstrating thus the strong influence of the environmental conditions on the mechanical properties of the cells. Copyright © 2017. Published by Elsevier Ltd.

Mechanisms of cellular invasion by intracellular parasites.

Science.gov (United States)

Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

2014-04-01

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

Mechanisms and cellular functions of intramembrane proteases.

Science.gov (United States)

Urban, Siniša

2013-12-01

The turn of the millennium coincided with the branding of a fundamentally different class of enzyme - proteases that reside immersed inside the membrane. This new field was the convergence of completely separate lines of research focused on cholesterol homeostasis, Alzheimer's disease, and developmental genetics. None intended their ultimate path, but soon became a richly-integrated fabric for an entirely new field: regulated intramembrane proteolysis. Our aim in this Special Issue is to focus on the ancient and nearly ubiquitous enzymes that catalyze this unexpected yet important reaction. The pace of progress has been dramatic, resulting in a rapidly-expanding universe of known cellular functions, and a paradigm shift in the biochemical understanding of these once heretical enzymes. More recently, the first therapeutic successes have been attained by targeting an intramembrane protease. We consider these advances and identify oncoming opportunities in four parts: growing spectra of cellular roles, insights into biochemical mechanisms, therapeutic strategies, and newly-emerging topics. Recent studies also expose challenges for the future, including non-linear relationships between substrate identification and physiological functions, and the need for potent and specific, not broad-class, inhibitors. © 2013.

Shoe midsole longitudinal bending stiffness and running economy, joint energy, and EMG.

Science.gov (United States)

Roy, Jean-Pierre R; Stefanyshyn, Darren J

2006-03-01

It has been shown that mechanical energy is dissipated at the metatarsophalangeal (MTP) joint during running and jumping. Furthermore, increasing the longitudinal bending stiffness of the midsole significantly reduced the energy dissipated at the MTP joint and increased jump performance. It was hypothesized that increasing midsole longitudinal bending stiffness would also lead to improvements in running economy. This study investigated the influence of midsole longitudinal bending stiffness on running economy (performance variable) and evaluated the local effects on joint energetics and muscular activity. Carbon fiber plates were inserted into running shoe midsoles and running economy, joint energy, and electromyographic (EMG) data were collected on 13 subjects. Approximately a 1% metabolic energy savings was observed when subjects ran in a stiff midsole relative to the control midsole. Subjects with a greater body mass had a greater decrease in oxygen consumption rates in the stiff midsole relative to the control midsole condition. The stiffer midsoles showed no significant differences in energy absorption at the MTP joint compared with the control shoe. Finally, no significant changes were observed in muscular activation. Increasing midsole longitudinal bending stiffness led to improvements in running economy, yet the underlying mechanisms that can be attributed to this improvement are still not fully understood.

Microstructure and mechanical properties of open-cellular biomaterials prototypes for total knee replacement implants fabricated by electron beam melting.

Science.gov (United States)

Murr, L E; Amato, K N; Li, S J; Tian, Y X; Cheng, X Y; Gaytan, S M; Martinez, E; Shindo, P W; Medina, F; Wicker, R B

2011-10-01

Total knee replacement implants consisting of a Co-29Cr-6Mo alloy femoral component and a Ti-6Al-4V tibial component are the basis for the additive manufacturing of novel solid, mesh, and foam monoliths using electron beam melting (EBM). Ti-6Al-4V solid prototype microstructures were primarily α-phase acicular platelets while the mesh and foam structures were characterized by α(')-martensite with some residual α. The Co-29Cr-6Mo containing 0.22% C formed columnar (directional) Cr(23)C(6) carbides spaced ~2 μm in the build direction, while HIP-annealed Co-Cr alloy exhibited an intrinsic stacking fault microstructure. A log-log plot of relative stiffness versus relative density for Ti-6Al-4V and Co-29Cr-6Mo open-cellular mesh and foams resulted in a fitted line with a nearly ideal slope, n = 2.1. A stress shielding design graph constructed from these data permitted mesh and foam implant prototypes to be fabricated for compatible bone stiffness. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of short-term isometric training on core/torso stiffness.

Science.gov (United States)

Lee, Benjamin; McGill, Stuart

2017-09-01

"Core" exercise is a basic part of many physical training regimens with goals ranging from rehabilitation of spine and knee injuries to improving athletic performance. Core stiffness has been proposed to perform several functions including reducing pain by minimising joint micro-movements, and enhancing strength and speed performance. This study probes the links between a training approach and immediate but temporary changes in stiffness. Passive and active stiffness was measured on 24 participants; 12 having little to no experience in core training (inexperienced), and the other 12 being athletes experienced to core training methods; before and after a 15 min bout of isometric core exercises. Passive stiffness was assessed on a "frictionless" bending apparatus and active stiffness assessed via a quick release mechanism. Short-term isometric core training increased passive and active stiffness in most directions for both inexperienced and experienced participants, passive left lateral bend among experienced participants being the exception (P core stiffness, in this case following a single session. This may influence performance and injury resilience for a brief period.

Dynamic Stiffness Transfer Function of an Electromechanical Actuator Using System Identification

Science.gov (United States)

Kim, Sang Hwa; Tahk, Min-Jea

2018-04-01

In the aeroelastic analysis of flight vehicles with electromechanical actuators (EMAs), an accurate prediction of flutter requires dynamic stiffness characteristics of the EMA. The dynamic stiffness transfer function of the EMA with brushless direct current (BLDC) motor can be obtained by conducting complicated mathematical calculations of control algorithms and mechanical/electrical nonlinearities using linearization techniques. Thus, system identification approaches using experimental data, as an alternative, have considerable advantages. However, the test setup for system identification is expensive and complex, and experimental procedures for data collection are time-consuming tasks. To obtain the dynamic stiffness transfer function, this paper proposes a linear system identification method that uses information obtained from a reliable dynamic stiffness model with a control algorithm and nonlinearities. The results of this study show that the system identification procedure is compact, and the transfer function is able to describe the dynamic stiffness characteristics of the EMA. In addition, to verify the validity of the system identification method, the simulation results of the dynamic stiffness transfer function and the dynamic stiffness model were compared with the experimental data for various external loads.

Porcine bladder acellular matrix (ACM): protein expression, mechanical properties

International Nuclear Information System (INIS)

Farhat, Walid A; Chen Jun; Haig, Jennifer; Antoon, Roula; Litman, Jessica; Yeger, Herman; Sherman, Christopher; Derwin, Kathleen

2008-01-01

Experimentally, porcine bladder acellular matrix (ACM) that mimics extracellular matrix has excellent potential as a bladder substitute. Herein we investigated the spatial localization and expression of different key cellular and extracellular proteins in the ACM; furthermore, we evaluated the inherent mechanical properties of the resultant ACM prior to implantation. Using a proprietary decellularization method, the DNA contents in both ACM and normal bladder were measured; in addition we used immunohistochemistry and western blots to quantify and localize the different cellular and extracellular components, and finally the mechanical testing was performed using a uniaxial mechanical testing machine. The mean DNA content in the ACM was significantly lower in the ACM compared to the bladder. Furthermore, the immunohistochemical and western blot analyses showed that collagen I and IV were preserved in the ACM, but possibly denatured collagen III in the ACM. Furthermore, elastin, laminin and fibronectin were mildly reduced in the ACM. Although the ACM did not exhibit nucleated cells, residual cellular components (actin, myosin, vimentin and others) were still present. There was, on the other hand, no significant difference in the mean stiffness between the ACM and the bladder. Although our decellularization method is effective in removing nuclear material from the bladder while maintaining its inherent mechanical properties, further work is mandatory to determine whether these residual DNA and cellular remnants would lead to any immune reaction, or if the mechanical properties of the ACM are preserved upon implantation and cellularization

Porcine bladder acellular matrix (ACM): protein expression, mechanical properties.

Science.gov (United States)

Farhat, Walid A; Chen, Jun; Haig, Jennifer; Antoon, Roula; Litman, Jessica; Sherman, Christopher; Derwin, Kathleen; Yeger, Herman

2008-06-01

Experimentally, porcine bladder acellular matrix (ACM) that mimics extracellular matrix has excellent potential as a bladder substitute. Herein we investigated the spatial localization and expression of different key cellular and extracellular proteins in the ACM; furthermore, we evaluated the inherent mechanical properties of the resultant ACM prior to implantation. Using a proprietary decellularization method, the DNA contents in both ACM and normal bladder were measured; in addition we used immunohistochemistry and western blots to quantify and localize the different cellular and extracellular components, and finally the mechanical testing was performed using a uniaxial mechanical testing machine. The mean DNA content in the ACM was significantly lower in the ACM compared to the bladder. Furthermore, the immunohistochemical and western blot analyses showed that collagen I and IV were preserved in the ACM, but possibly denatured collagen III in the ACM. Furthermore, elastin, laminin and fibronectin were mildly reduced in the ACM. Although the ACM did not exhibit nucleated cells, residual cellular components (actin, myosin, vimentin and others) were still present. There was, on the other hand, no significant difference in the mean stiffness between the ACM and the bladder. Although our decellularization method is effective in removing nuclear material from the bladder while maintaining its inherent mechanical properties, further work is mandatory to determine whether these residual DNA and cellular remnants would lead to any immune reaction, or if the mechanical properties of the ACM are preserved upon implantation and cellularization.

Porcine bladder acellular matrix (ACM): protein expression, mechanical properties

Energy Technology Data Exchange (ETDEWEB)

Farhat, Walid A [Department of Surgery, Division of Urology, University of Toronto and Hospital for Sick Children, Toronto, ON M5G 1X8 (Canada); Chen Jun; Haig, Jennifer; Antoon, Roula; Litman, Jessica; Yeger, Herman [Department of Developmental and Stem Cell Biology, Research Institute, Hospital for Sick Children, Toronto, ON M5G 1X8 (Canada); Sherman, Christopher [Department of Anatomic Pathology, Sunnybrook and Women' s College Health Sciences Centre, Toronto, ON (Canada); Derwin, Kathleen [Department of Biomedical Engineering, Lerner Research Institute and Orthopaedic Research Center, Cleveland Clinic Foundation, Cleveland, OH (United States)], E-mail: walid.farhat@sickkids.ca

2008-06-01

Experimentally, porcine bladder acellular matrix (ACM) that mimics extracellular matrix has excellent potential as a bladder substitute. Herein we investigated the spatial localization and expression of different key cellular and extracellular proteins in the ACM; furthermore, we evaluated the inherent mechanical properties of the resultant ACM prior to implantation. Using a proprietary decellularization method, the DNA contents in both ACM and normal bladder were measured; in addition we used immunohistochemistry and western blots to quantify and localize the different cellular and extracellular components, and finally the mechanical testing was performed using a uniaxial mechanical testing machine. The mean DNA content in the ACM was significantly lower in the ACM compared to the bladder. Furthermore, the immunohistochemical and western blot analyses showed that collagen I and IV were preserved in the ACM, but possibly denatured collagen III in the ACM. Furthermore, elastin, laminin and fibronectin were mildly reduced in the ACM. Although the ACM did not exhibit nucleated cells, residual cellular components (actin, myosin, vimentin and others) were still present. There was, on the other hand, no significant difference in the mean stiffness between the ACM and the bladder. Although our decellularization method is effective in removing nuclear material from the bladder while maintaining its inherent mechanical properties, further work is mandatory to determine whether these residual DNA and cellular remnants would lead to any immune reaction, or if the mechanical properties of the ACM are preserved upon implantation and cellularization.

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

Energy Technology Data Exchange (ETDEWEB)

Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

2012-07-06

Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

International Nuclear Information System (INIS)

Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

2012-01-01

Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

Cellular mechanisms of noise-induced hearing loss.

Science.gov (United States)

Kurabi, Arwa; Keithley, Elizabeth M; Housley, Gary D; Ryan, Allen F; Wong, Ann C-Y

2017-06-01

Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation. Published by Elsevier B.V.

Dynamically tuned magnetostrictive spring with electrically controlled stiffness

Science.gov (United States)

Scheidler, Justin J.; Asnani, Vivake M.; Dapino, Marcelo J.

2016-03-01

This paper presents the design and testing of an electrically controllable magnetostrictive spring that has a dynamically tunable stiffness (i.e., a magnetostrictive Varispring). The device enables in situ stiffness tuning or stiffness switching for vibration control applications. Using a nonlinear electromechanical transducer model and an analytical solution of linear, mechanically induced magnetic diffusion, Terfenol-D is shown to have a faster rise time to stepped voltage inputs and a significantly higher magnetic diffusion cut-off frequency relative to Galfenol. A Varispring is manufactured using a laminated Terfenol-D rod. Further rise time reductions are achieved by minimizing the rod’s diameter and winding the electromagnet with larger wire. Dynamic tuning of the Varispring’s stiffness is investigated by measuring the Terfenol-D rod’s strain response to dynamic, compressive, axial forces in the presence of sinusoidal or square wave control currents. The Varispring’s rise time is \\lt 1 ms for 1 A current switches. Continuous modulus changes up to 21.9 GPa and 500 Hz and square wave modulus changes (dynamic {{Δ }}E effect) up to 12.3 GPa and 100 Hz are observed. Stiffness tunability and tuning bandwidth can be considerably increased by operating about a more optimal bias stress and improving the control of the electrical input.

Cellular and molecular mechanisms of metformin: an overview

Science.gov (United States)

Viollet, Benoit; Guigas, Bruno; Sanz Garcia, Nieves; Leclerc, Jocelyne; Foretz, Marc; Andreelli, Fabrizio

2012-01-01

Considerable efforts have been made since the 1950s to better understand the cellular and molecular mechanisms of action of metformin, a potent antihyperglycemic agent now recommended as the first line oral therapy for type 2 diabetes (T2D). The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory-chain complex 1. In addition, the resulting decrease in hepatic energy status activates the AMP-activated protein kinase (AMPK), a cellular metabolic sensor, providing a generally accepted mechanism for metformin action on hepatic gluconeogenic program. The demonstration that the respiratory-chain complex 1, but not AMPK, is the primary target of metformin was recently strengthened by showing that the metabolic effect of the drug is preserved in liver-specific AMPK-deficient mice. Beyond its effect on glucose metabolism, metformin was reported to restore ovarian function in polycystic ovary syndrome, reduce fatty liver and to lower microvascular and macrovascular complications associated with T2D. Its use was also recently suggested as an adjuvant treatment for cancer or gestational diabetes, and for the prevention in pre-diabetic populations. These emerging new therapeutic areas for metformin will be reviewed together with recent data from pharmacogenetic studies linking genetic variations to drug response, a promising new step towards personalized medicine in the treatment of T2D. PMID:22117616

Development of a stiffness-angle law for simplifying the measurement of human hair stiffness.

Science.gov (United States)

Jung, I K; Park, S C; Lee, Y R; Bin, S A; Hong, Y D; Eun, D; Lee, J H; Roh, Y S; Kim, B M

2018-04-01

This research examines the benefits of caffeine absorption on hair stiffness. To test hair stiffness, we have developed an evaluation method that is not only accurate, but also inexpensive. Our evaluation method for measuring hair stiffness culminated in a model, called the Stiffness-Angle Law, which describes the elastic properties of hair and can be widely applied to the development of hair care products. Small molecules (≤500 g mol -1 ) such as caffeine can be absorbed into hair. A common shampoo containing 4% caffeine was formulated and applied to hair 10 times, after which the hair stiffness was measured. The caffeine absorption of the treated hair was observed using Fourier-transform infrared spectroscopy (FTIR) with a focal plane array (FPA) detector. Our evaluation method for measuring hair stiffness consists of a regular camera and a support for single strands of hair. After attaching the hair to the support, the bending angle of the hair was observed with a camera and measured. Then, the hair strand was weighed. The stiffness of the hair was calculated based on our proposed Stiffness-Angle Law using three variables: angle, weight of hair and the distance the hair was pulled across the support. The caffeine absorption was confirmed by FTIR analysis. The concentration of amide bond in the hair certainly increased due to caffeine absorption. After caffeine was absorbed into the hair, the bending angle and weight of the hair changed. Applying these measured changes to the Stiffness-Angle Law, it was confirmed that the hair stiffness increased by 13.2% due to caffeine absorption. The theoretical results using the Stiffness-Angle Law agree with the visual examinations of hair exposed to caffeine and also the known results of hair stiffness from a previous report. Our evaluation method combined with our proposed Stiffness-Angle Law effectively provides an accurate and inexpensive evaluation technique for measuring bending stiffness of human hair. © 2018

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

Science.gov (United States)

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

Posttraumatic stiff elbow

Directory of Open Access Journals (Sweden)

Ravi Mittal

2017-01-01

Full Text Available Posttraumatic stiff elbow is a frequent and disabling complication and poses serious challenges for its management. In this review forty studies were included to know about the magnitude of the problem, causes, pathology, prevention, and treatment of posttraumatic stiff elbow. These studies show that simple measures such as internal fixation, immobilization in extension, and early motion of elbow joint are the most important steps that can prevent elbow stiffness. It also supports conservative treatment in selected cases. There are no clear guidelines about the choice between the numerous procedures described in literature. However, this review article disproves two major beliefs-heterotopic ossification is a bad prognostic feature, and passive mobilization of elbow causes elbow stiffness.

Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

Science.gov (United States)

Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

2015-03-01

Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cellular studies and interaction mechanisms of extremely low frequency fields

Science.gov (United States)

Liburdy, Robert P.

1995-01-01

Worldwide interest in the biological effects of ELF (extremely low frequency, level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E) or the magnetic (B) field, or if combinations of static B and time-varying B fields represent an exposure metric for the cell. This question relates directly to understanding fundamental interaction mechanisms and to the development of a rationale for ELF dose threshold guidelines. The weight of

Probabilistic cellular automata: Some statistical mechanical considerations

International Nuclear Information System (INIS)

Lebowitz, J.L.; Maes, C.; Speer, E.R.

1990-01-01

Spin systems evolving in continuous or discrete time under the action of stochastic dynamics are used to model phenomena as diverse as the structure of alloys and the functioning of neural networks. While in some cases the dynamics are secondary, designed to produce a specific stationary measure whose properties one is interested in studying, there are other cases in which the only available information is the dynamical rule. Prime examples of the former are computer simulations, via Glauber dynamics, of equilibrium Gibbs measures with a specified interaction potential. Examples of the latter include various types of majority rule dynamics used as models for pattern recognition and for error-tolerant computations. The present note discusses ways in which techniques found useful in equilibrium statistical mechanics can be applied to a particular class of models of the latter types. These are cellular automata with noise: systems in which the spins are updated stochastically at integer times, simultaneously at all sites of some regular lattice. These models were first investigated in detail in the Soviet literature of the late sixties and early seventies. They are now generally referred to as Stochastic or Probabilistic Cellular Automata (PCA), and may be considered to include deterministic automata (CA) as special limits. 16 refs., 3 figs

Vascular Stiffness and Increased Pulse Pressure in the Aging Cardiovascular System

Directory of Open Access Journals (Sweden)

Jochen Steppan

2011-01-01

Full Text Available Aging leads to a multitude of changes in the cardiovascular system, including systolic hypertension, increased central vascular stiffness, and increased pulse pressure. In this paper we will review the effects of age-associated increased vascular stiffness on systolic blood pressure, pulse pressure, augmentation index, and cardiac workload. Additionally we will describe pulse wave velocity as a method to measure vascular stiffness and review the impact of increased vascular stiffness as an index of vascular health and as a predictor of adverse cardiovascular outcomes. Furthermore, we will discuss the underlying mechanisms and how these may be modified in order to change the outcomes. A thorough understanding of these concepts is of paramount importance and has therapeutic implications for the increasingly elderly population.

Compression behavior of cellular metals with inhomogeneous mass distribution

International Nuclear Information System (INIS)

Foroughi, B.

2001-05-01

Mechanical behavior of two types of closed cell metals (ALULIGHT and ALPORAS) is investigated experimentally and numerically. Compressive tests performed on prismatic specimens indicate that inhomogeneities in the mass density distribution are a key factor in the deformation behavior of cellular metals. The three dimensional cellular structure of the investigated specimens is recorded using x-ray medical computed tomography (CT). A special procedure called density mapping method has been used to transfer the recorded CT data into a continuum by averaging over a certain domain (averaging domain). This continuum model is implemented using finite elements to study the effect of variations in local mass densities. The finite element model is performed by a simple regular discretization of a specimen's volume with elements which have constant edge length. Mechanical properties derived from compression tests of ALPORAS samples are assigned to the corresponding mesoscopic density value of each element. The effect of averaging domain size is studied to obtain a suitable dimension which fulfils the homogenization requirements and allows the evaluation of inhomogenities in the specimens. The formation and propagation of deformation band(s) and stress-strain responses of tested cellular metals are modeled with respect to their mass distribution. It is shown that the inhomogeneous density distribution leads to plastic strain localization and causes a monotonically increase of the stress in the plateau regime although no hardening response was considered for homogeneous material in this regime. The simulated plastic strain localization and the calculated stress-strain responses are compared with the experimental results. The stiffness values of experiment and simulation agree very well for both cellular materials. The values of plateau strength as well, but it differs in some cases of ALULIGHT samples, where the hardening response can be predicted at least qualitatively

Cellular and molecular mechanisms coordinating pancreas development.

Science.gov (United States)

Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

2017-08-15

The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

Effect of Shoes on Stiffness and Energy Efficiency of Ankle-Foot Orthosis: Bench Testing Analysis.

Science.gov (United States)

Kobayashi, Toshiki; Gao, Fan; LeCursi, Nicholas; Foreman, K Bo; Orendurff, Michael S

2017-12-01

Understanding the mechanical properties of ankle-foot orthoses (AFOs) is important to maximize their benefit for those with movement disorders during gait. Though mechanical properties such as stiffness and/or energy efficiency of AFOs have been extensively studied, it remains unknown how and to what extent shoes influence their properties. The aim of this study was to investigate the effect of shoes on stiffness and energy efficiency of an AFO using a custom mechanical testing device. Stiffness and energy efficiency of the AFO were measured in the plantar flexion and dorsiflexion range, respectively, under AFO-alone and AFO-Shoe combination conditions. The results of this study demonstrated that the stiffness of the AFO-Shoe combination was significantly decreased compared to the AFO-alone condition, but no significant differences were found in energy efficiency. From the results, we recommend that shoes used with AFOs should be carefully selected not only based on their effect on alignment of the lower limb, but also their effects on overall mechanical properties of the AFO-Shoe combination. Further study is needed to clarify the effects of differences in shoe designs on AFO-Shoe combination mechanical properties.

Spatially varying small-strain stiffness in soils subjected to K0 loading

KAUST Repository

Kim, Hyun-Ki; Santamarina, Carlos

2017-01-01

Grain-scale characteristics and formation history determine spatial variability in granular masses. We investigate the effect of spatially varying stiffness on the load-deformation response under zero-lateral strain conditions using numerical simulations of correlated random fields, where the granular medium is represented by a non-linear stress-dependent meso-scale model. Results show that stiffness heterogeneity results in higher global compressibility as compared to the homogeneous medium with the same arithmetic mean stiffness. Furthermore, the non-homogeneous stress field that develops inside the granular mass is characterized by focused load transfer along columnar regions, higher stress anisotropy and lower horizontal-to-vertical stress ratio K0 than in a granular medium of homogenous stiffness. As the applied stress increases, the inherent stress-dependent response of the granular material leads to a more homogenous stress field. While greater variance in stiffness causes lower global stiffness, a longer correlation length results in greater variance in global mechanical response among multiple realizations.

Spatially varying small-strain stiffness in soils subjected to K0 loading

KAUST Repository

Kim, Hyun-Ki

2017-08-08

Grain-scale characteristics and formation history determine spatial variability in granular masses. We investigate the effect of spatially varying stiffness on the load-deformation response under zero-lateral strain conditions using numerical simulations of correlated random fields, where the granular medium is represented by a non-linear stress-dependent meso-scale model. Results show that stiffness heterogeneity results in higher global compressibility as compared to the homogeneous medium with the same arithmetic mean stiffness. Furthermore, the non-homogeneous stress field that develops inside the granular mass is characterized by focused load transfer along columnar regions, higher stress anisotropy and lower horizontal-to-vertical stress ratio K0 than in a granular medium of homogenous stiffness. As the applied stress increases, the inherent stress-dependent response of the granular material leads to a more homogenous stress field. While greater variance in stiffness causes lower global stiffness, a longer correlation length results in greater variance in global mechanical response among multiple realizations.

Postischemic revascularization: from cellular and molecular mechanisms to clinical applications.

Science.gov (United States)

Silvestre, Jean-Sébastien; Smadja, David M; Lévy, Bernard I

2013-10-01

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

The Role of Instabilities on the Mechanical Response of Cellular Solids and Structures

National Research Council Canada - National Science Library

Kyriakides, S

1997-01-01

.... The relatively regular and periodic microstructure of these two-dimensional materials makes them excellent models for studying the mechanisms that govern the compressive response of cellular materials...

A linear stepping endovascular intervention robot with variable stiffness and force sensing.

Science.gov (United States)

He, Chengbin; Wang, Shuxin; Zuo, Siyang

2018-03-08

Robotic-assisted endovascular intervention surgery has attracted significant attention and interest in recent years. However, limited designs have focused on the variable stiffness mechanism of the catheter shaft. Flexible catheter needs to be partially switched to a rigid state that can hold its shape against external force to achieve a stable and effective insertion procedure. Furthermore, driving catheter in a similar way with manual procedures has the potential to make full use of the extensive experience from conventional catheter navigation. Besides driving method, force sensing is another significant factor for endovascular intervention. This paper presents a variable stiffness catheterization system that can provide stable and accurate endovascular intervention procedure with a linear stepping mechanism that has a similar operation mode to the conventional catheter navigation. A specially designed shape-memory polymer tube with water cooling structure is used to achieve variable stiffness of the catheter. Hence, four FBG sensors are attached to the catheter tip in order to monitor the tip contact force situation with temperature compensation. Experimental results show that the actuation unit is able to deliver linear and rotational motions. We have shown the feasibility of FBG force sensing to reduce the effect of temperature and detect the tip contact force. The designed catheter can change its stiffness partially, and the stiffness of the catheter can be remarkably increased in rigid state. Hence, in the rigid state, the catheter can hold its shape against a [Formula: see text] load. The prototype has also been validated with a vascular phantom, demonstrating the potential clinical value of the system. The proposed system provides important insights into the design of compact robotic-assisted catheter incorporating effective variable stiffness mechanism and real-time force sensing for intraoperative endovascular intervention.

Effect of long-term isometric training on core/torso stiffness.

Science.gov (United States)

Lee, Benjamin C Y; McGill, Stuart M

2015-06-01

Although core stiffness enhances athletic performance traits, controversy exists regarding the effectiveness of isometric vs. dynamic core training methods. This study aimed to determine whether long-term changes in stiffness can be trained, and if so, what is the most effective method. Twenty-four healthy male subjects (23 ± 3 years; 1.8 ± 0.06 m; 77.5 ± 10.8 kg) were recruited for passive and active stiffness measurements before and after a 6-week core training intervention. Twelve subjects (22 ± 2 years; 1.8 ± 0.08 m; 78.3 ± 12.3 kg) were considered naive to physical and core exercise. The other 12 subjects (24 ± 3 years; 1.8 ± 0.05 m; 76.8 ± 9.7 kg) were Muay Thai athletes (savvy). A repeated-measures design compared core training methods (isometric vs. dynamic, with a control group) and subject training experience (naive vs. savvy) before and after a 6-week training period. Passive stiffness was assessed on a "frictionless" bending apparatus and active stiffness assessed through a quick release mechanism. Passive stiffness increased after the isometric training protocol. Dynamic training produced a smaller effect, and as expected, there was no change in the control group. Active stiffness did not change in any group. Comparisons between subject and training groups did not reveal any interactions. Thus, an isometric training approach was superior in terms of enhancing core stiffness. This is important since increased core stiffness enhances load bearing ability, arrests painful vertebral micromovements, and enhances ballistic distal limb movement. This may explain the efficacy reported for back and knee injury reduction.

Approaching a universal scaling relationship between fracture stiffness and fluid flow

Science.gov (United States)

Pyrak-Nolte, Laura J.; Nolte, David D.

2016-02-01

A goal of subsurface geophysical monitoring is the detection and characterization of fracture alterations that affect the hydraulic integrity of a site. Achievement of this goal requires a link between the mechanical and hydraulic properties of a fracture. Here we present a scaling relationship between fluid flow and fracture-specific stiffness that approaches universality. Fracture-specific stiffness is a mechanical property dependent on fracture geometry that can be monitored remotely using seismic techniques. A Monte Carlo numerical approach demonstrates that a scaling relationship exists between flow and stiffness for fractures with strongly correlated aperture distributions, and continues to hold for fractures deformed by applied stress and by chemical erosion as well. This new scaling relationship provides a foundation for simulating changes in fracture behaviour as a function of stress or depth in the Earth and will aid risk assessment of the hydraulic integrity of subsurface sites.

Prediction of the time course of callus stiffness as a function of mechanical parameters in experimental rat fracture healing studies--a numerical study.

Directory of Open Access Journals (Sweden)

Tim Wehner

Full Text Available Numerous experimental fracture healing studies are performed on rats, in which different experimental, mechanical parameters are applied, thereby prohibiting direct comparison between each other. Numerical fracture healing simulation models are able to predict courses of fracture healing and offer support for pre-planning animal experiments and for post-hoc comparison between outcomes of different in vivo studies. The aims of this study are to adapt a pre-existing fracture healing simulation algorithm for sheep and humans to the rat, to corroborate it using the data of numerous different rat experiments, and to provide healing predictions for future rat experiments. First, material properties of different tissue types involved were adjusted by comparing experimentally measured callus stiffness to respective simulated values obtained in three finite element (FE models. This yielded values for Young's moduli of cortical bone, woven bone, cartilage, and connective tissue of 15,750 MPa, 1,000 MPa, 5 MPa, and 1 MPa, respectively. Next, thresholds in the underlying mechanoregulatory tissue differentiation rules were calibrated by modifying model parameters so that predicted fracture callus stiffness matched experimental data from a study that used rigid and flexible fixators. This resulted in strain thresholds at higher magnitudes than in models for sheep and humans. The resulting numerical model was then used to simulate numerous fracture healing scenarios from literature, showing a considerable mismatch in only 6 of 21 cases. Based on this corroborated model, a fit curve function was derived which predicts the increase of callus stiffness dependent on bodyweight, fixation stiffness, and fracture gap size. By mathematically predicting the time course of the healing process prior to the animal studies, the data presented in this work provides support for planning new fracture healing experiments in rats. Furthermore, it allows one to transfer and

Longitudinal relaxation of initially straight flexible and stiff polymers

Science.gov (United States)

Dimitrakopoulos, Panagiotis; Dissanayake, Inuka

2004-11-01

The present talk considers the relaxation of a single flexible or stiff polymer chain from an initial straight configuration in a viscous solvent. This problem commonly arises when strong flows are turned off in both industrial and biological applications. The problem is also motivated by recent experiments with single biopolymer molecules relaxing after being fully extended by applied forces as well as by the recent development of micro-devices involving stretched tethered biopolymers. Our results are applicable to a wide array of synthetic polymers such as polyacrylamides, Kevlar and polyesters as well as biopolymers such as DNA, actin filaments, microtubules and MTV. In this talk we discuss the mechanism of the polymer relaxation as was revealed through Brownian Dynamics simulations covering a broad range of time scales and chain stiffness. After the short-time free diffusion, the chain's longitudinal reduction at early intermediate times is shown to constitute a universal behavior for any chain stiffness caused by a quasi-steady relaxation of tensions associated with the deforming action of the Brownian forces. Stiff chains are shown to exhibit a late intermediate-time longitudinal reduction associated with a relaxation of tensions affected by the deforming Brownian and the restoring bending forces. The longitudinal and transverse relaxations are shown to obey different laws, i.e. the chain relaxation is anisotropic at all times. In the talk, we show how from the knowledge of the relaxation mechanism, we can predict and explain the polymer properties including the polymer stress and the solution birefringence. In addition, a generalized stress-optic law is derived valid for any time and chain stiffness. All polymer properties which depend on the polymer length are shown to exhibit two intermediate-time behaviors with the early one to constitute a universal behavior for any chain stiffness. This work was supported in part by the Minta Martin Research Fund. The

Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

Science.gov (United States)

Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

2013-01-01

This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

Cellular mechanisms of estradiol-mediated sexual differentiation of the brain.

Science.gov (United States)

Wright, Christopher L; Schwarz, Jaclyn S; Dean, Shannon L; McCarthy, Margaret M

2010-09-01

Gonadal steroids organize the developing brain during a perinatal sensitive period and have enduring consequences for adult behavior. In male rodents testicular androgens are aromatized in neurons to estrogens and initiate multiple distinct cellular processes that ultimately determine the masculine phenotype. Within specific brain regions, overall cell number and dendritic morphology are the principal targets for hormonal organization. Recent advances have been made in elucidating the cellular mechanisms by which the neurological underpinnings of sexually dimorphic physiology and behavior are determined. These include estradiol-mediated prostaglandin synthesis, presynaptic release of glutamate, postsynaptic changes in glutamate receptors and changes in cell adhesion molecules. Sex differences in cell death are mediated by hormonal modulation of survival and death factors such as TNFalpha and Bcl-2/BAX. Copyright 2010 Elsevier Ltd. All rights reserved.

Cellular packing, mechanical stress and the evolution of multicellularity

Science.gov (United States)

Jacobeen, Shane; Pentz, Jennifer T.; Graba, Elyes C.; Brandys, Colin G.; Ratcliff, William C.; Yunker, Peter J.

2018-03-01

The evolution of multicellularity set the stage for sustained increases in organismal complexity1-5. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters6-8 fracture due to crowding-induced mechanical stress. Over seven weeks ( 291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size—a fundamental step in the evolution of multicellularity.

Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT.

Science.gov (United States)

Alomari, Ali Hamed; Wille, Marie-Luise; Langton, Christian M

2018-02-01

Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm -1 ) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS) parameters of velocity and attenuation are dependent upon both bone quantity and bone quality, although it has not been possible to date to transpose one particular QUS parameter into separate estimates of quantity and quality. It has recently been shown that ultrasound transit time spectroscopy (UTTS) may provide an accurate estimate of bone density and hence quantity. We hypothesised that UTTS also has the potential to provide an estimate of bone structure and hence quality. In this in-vitro study, 16 human femoral bone samples were tested utilising three techniques; UTTS, micro computed tomography (μCT), and mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV) and two novel structural parameters, inter-quartile range of the derived transit time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP). μCT was utilised to derive BV/TV along with several bone structure parameters. A destructive mechanical test was utilised to measure the stiffness and strength (failure load) of the bone samples. BV/TV was calculated from the derived transit time spectrum (TTS); the correlation coefficient (R 2 ) with μCT-BV/TV was 0.885. For predicting mechanical stiffness and strength, BV/TV derived by both μCT and UTTS provided the strongest correlation with mechanical stiffness (R 2 =0.567 and 0.618 respectively) and

The Effects of Chronological Age on the Cellular Mechanics of Human Dermal Fibroblasts

Science.gov (United States)

Pan, Z.; Hung, V.; Kambhampati, S.; Ge, S. R.; Rafailovich, M.; Ghosh, K.; Clark, R.; Liu, Y. J.; Nakamura, T.; Shu, X. Z.; Prestwich, G.

2006-03-01

It is often observed that older people display diminished wound healing abilities. Understanding of this phenomenon is important for many in vivo applications of tissue engineering. In this study, the cell mechanics of dermal fibroblasts from 25, 40 and 84 years old female subjects were compared. These cells were cultured on functionalized hyaluronic acid hydrogel substrates which emulated physiological conditions in dermal tissue. The deformation of the substrate caused by cellular traction forces was detected by tracing the displacement of fluorescent beads embedded in the substrate using Digital Image Speckle Correlation. Then cellular traction forces were quantitatively determined by Finite Element Method in a linear elastic model with a high spatial resolution. These results were correlated with auxiliary measurements of substrate modulus, cell modulus and migration. We found that with increasing age, the magnitude of the cellular traction forces diminished. Similarly, the ability of the cells to adapt to changes in the mechanical properties of their environment and migrate was also impaired. The interrelationship between these factors and wound healing will be discussed. This work is supported by NSF- MRSEC program.

Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

Science.gov (United States)

Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

2015-09-01

The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

Electrothermally Actuated Microbeams With Varying Stiffness

KAUST Repository

Tella, Sherif Adekunle

2017-11-03

We present axially loaded clamped-guided microbeams that can be used as resonators and actuators of variable stiffness, actuation, and anchor conditions. The applied axial load is implemented by U-shaped electrothermal actuators stacked at one of the beams edges. These can be configured and wired in various ways, which serve as mechanical stiffness elements that control the operating resonance frequency of the structures and their static displacement. The experimental results have shown considerable increase in the resonance frequency and mid-point deflection of the microbeam upon changing the end conditions of the beam. These results can be promising for applications requiring large deflection and high frequency tunability, such as filters, memory devices, and switches. The experimental results are compared to multi-physics finite-element simulations showing good agreement among them.

Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

Science.gov (United States)

Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

2015-07-01

A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanosensation across borders: fibroblasts inside a macroporous scaffold sense and respond to the mechanical environment beyond the scaffold walls.

Science.gov (United States)

Könnig, D; Herrera, A; Duda, G N; Petersen, A

2018-01-01

In tissue defects, cells face distinct mechanical boundary conditions, but how this influences early stages of tissue regeneration remains largely unknown. Biomaterials are used to fill defects but also to provide specific mechanical or geometrical signals. However, they might at the same time shield mechanical information from surrounding tissues that is relevant for tissue functionalisation. This study investigated how fibroblasts in a soft macroporous biomaterial scaffold respond to distinct mechanical environments while they form microtissues. Different boundary stiffnesses counteracting scaffold contraction were provided via a newly developed in vitro setup. Online monitoring over 14 days revealed 3.0 times lower microtissue contraction but 1.6 times higher contraction force for high vs. low stiffness. This difference was significant already after 48 h, a very early stage of microtissue growth. The microtissue's mechanical and geometrical adaptation indicated a collective cellular behaviour and mechanical communication across scaffold pore walls. Surprisingly, the stiffness of the environment influenced cell behaviour even inside macroporous scaffolds where direct cell-cell contacts are hindered. Mechanical communication between cells via traction forces is essential for tissue adaptation to the environment and should not be blocked by rigid biomaterials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Natural agents: cellular and molecular mechanisms of photoprotection.

Science.gov (United States)

Afaq, Farrukh

2011-04-15

The skin is the largest organ of the body that produces a flexible and self-repairing barrier and protects the body from most common potentially harmful physical, environmental, and biological insults. Solar ultraviolet (UV) radiation is one of the major environmental insults to the skin and causes multi-tiered cellular and molecular events eventually leading to skin cancer. The past decade has seen a surge in the incidence of skin cancer due to changes in life style patterns that have led to a significant increase in the amount of UV radiation that people receive. Reducing excessive exposure to UV radiation is desirable; nevertheless this approach is not easy to implement. Therefore, there is an urgent need to develop novel strategies to reduce the adverse biological effects of UV radiation on the skin. A wide variety of natural agents have been reported to possess substantial skin photoprotective effects. Numerous preclinical and clinical studies have elucidated that natural agents act by several cellular and molecular mechanisms to delay or prevent skin cancer. In this review article, we have summarized and discussed some of the selected natural agents for skin photoprotection. Copyright © 2010 Elsevier Inc. All rights reserved.

Estimating Gear Teeth Stiffness

DEFF Research Database (Denmark)

Pedersen, Niels Leergaard

2013-01-01

The estimation of gear stiffness is important for determining the load distribution between the gear teeth when two sets of teeth are in contact. Two factors have a major influence on the stiffness; firstly the boundary condition through the gear rim size included in the stiffness calculation...... and secondly the size of the contact. In the FE calculation the true gear tooth root profile is applied. The meshing stiffness’s of gears are highly non-linear, it is however found that the stiffness of an individual tooth can be expressed in a linear form assuming that the contact length is constant....

Breast tissue stiffness estimation for surgical guidance using gravity-induced excitation.

Science.gov (United States)

Griesenauer, Rebekah H; Weis, Jared A; Arlinghaus, Lori R; Meszoely, Ingrid M; Miga, Michael I

2017-06-21

Tissue stiffness interrogation is fundamental in breast cancer diagnosis and treatment. Furthermore, biomechanical models for predicting breast deformations have been created for several breast cancer applications. Within these applications, constitutive mechanical properties must be defined and the accuracy of this estimation directly impacts the overall performance of the model. In this study, we present an image-derived computational framework to obtain quantitative, patient specific stiffness properties for application in image-guided breast cancer surgery and interventions. The method uses two MR acquisitions of the breast in different supine gravity-loaded configurations to fit mechanical properties to a biomechanical breast model. A reproducibility assessment of the method was performed in a test-retest study using healthy volunteers and was further characterized in simulation. In five human data sets, the within subject coefficient of variation ranged from 10.7% to 27% and the intraclass correlation coefficient ranged from 0.91-0.944 for assessment of fibroglandular and adipose tissue stiffness. In simulation, fibroglandular content and deformation magnitude were shown to have significant effects on the shape and convexity of the objective function defined by image similarity. These observations provide an important step forward in characterizing the use of nonrigid image registration methodologies in conjunction with biomechanical models to estimate tissue stiffness. In addition, the results suggest that stiffness estimation methods using gravity-induced excitation can reliably and feasibly be implemented in breast cancer surgery/intervention workflows.

Breast tissue stiffness estimation for surgical guidance using gravity-induced excitation

Science.gov (United States)

Griesenauer, Rebekah H.; Weis, Jared A.; Arlinghaus, Lori R.; Meszoely, Ingrid M.; Miga, Michael I.

2017-06-01

Tissue stiffness interrogation is fundamental in breast cancer diagnosis and treatment. Furthermore, biomechanical models for predicting breast deformations have been created for several breast cancer applications. Within these applications, constitutive mechanical properties must be defined and the accuracy of this estimation directly impacts the overall performance of the model. In this study, we present an image-derived computational framework to obtain quantitative, patient specific stiffness properties for application in image-guided breast cancer surgery and interventions. The method uses two MR acquisitions of the breast in different supine gravity-loaded configurations to fit mechanical properties to a biomechanical breast model. A reproducibility assessment of the method was performed in a test-retest study using healthy volunteers and was further characterized in simulation. In five human data sets, the within subject coefficient of variation ranged from 10.7% to 27% and the intraclass correlation coefficient ranged from 0.91-0.944 for assessment of fibroglandular and adipose tissue stiffness. In simulation, fibroglandular content and deformation magnitude were shown to have significant effects on the shape and convexity of the objective function defined by image similarity. These observations provide an important step forward in characterizing the use of nonrigid image registration methodologies in conjunction with biomechanical models to estimate tissue stiffness. In addition, the results suggest that stiffness estimation methods using gravity-induced excitation can reliably and feasibly be implemented in breast cancer surgery/intervention workflows.

The soft mechanical signature of glial scars in the central nervous system

Science.gov (United States)

Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James; Franze, Kristian

2017-03-01

Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.

Stiff, light, strong and ductile: nano-structured High Modulus Steel.

Science.gov (United States)

Springer, H; Baron, C; Szczepaniak, A; Uhlenwinkel, V; Raabe, D

2017-06-05

Structural material development for lightweight applications aims at improving the key parameters strength, stiffness and ductility at low density, but these properties are typically mutually exclusive. Here we present how we overcome this trade-off with a new class of nano-structured steel - TiB 2 composites synthesised in-situ via bulk metallurgical spray-forming. Owing to the nano-sized dispersion of the TiB 2 particles of extreme stiffness and low density - obtained by the in-situ formation with rapid solidification kinetics - the new material has the mechanical performance of advanced high strength steels, and a 25% higher stiffness/density ratio than any of the currently used high strength steels, aluminium, magnesium and titanium alloys. This renders this High Modulus Steel the first density-reduced, high stiffness, high strength and yet ductile material which can be produced on an industrial scale. Also ideally suited for 3D printing technology, this material addresses all key requirements for high performance and cost effective lightweight design.

Artificial muscles with adjustable stiffness

International Nuclear Information System (INIS)

Mutlu, Rahim; Alici, Gursel

2010-01-01

This paper reports on a stiffness enhancement methodology based on using a suitably designed contact surface with which cantilevered-type conducting polymer bending actuators are in contact during operation. The contact surface constrains the bending behaviour of the actuators. Depending on the topology of the contact surface, the resistance of the polymer actuators to deformation, i.e. stiffness, is varied. As opposed to their predecessors, these polymer actuators operate in air. Finite element analysis and modelling are used to quantify the effect of the contact surface on the effective stiffness of a trilayer cantilevered beam, which represents a one-end-free, the-other-end-fixed polypyrrole (PPy) conducting polymer actuator under a uniformly distributed load. After demonstrating the feasibility of the adjustable stiffness concept, experiments were conducted to determine the stiffness of bending-type conducting polymer actuators in contact with a range (20–40 mm in radius) of circular contact surfaces. The numerical and experimental results presented demonstrate that the stiffness of the actuators can be varied using a suitably profiled contact surface. The larger the radius of the contact surface is, the higher is the stiffness of the polymer actuators. The outcomes of this study suggest that, although the stiffness of the artificial muscles considered in this study is constant for a given geometric size, and electrical and chemical operation conditions, it can be changed in a nonlinear fashion to suit the stiffness requirement of a considered application. The stiffness enhancement methodology can be extended to other ionic-type conducting polymer actuators

Resveratrol Inhibition of Cellular Respiration: New Paradigm for an Old Mechanism

Directory of Open Access Journals (Sweden)

Luis Alberto Madrigal-Perez

2016-03-01

Full Text Available Resveratrol (3,4′,5-trihydroxy-trans-stilbene, RSV has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1 decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2 increases adenosine monophosphate/adenosine diphosphate (AMP/ADP ratio that can lead to AMP protein kinase (AMPK activation, which is related to its health effects, and (3 increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.

A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

Science.gov (United States)

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. PMID:25999313

A variable stiffness joint with electrospun P(VDF-TrFE-CTFE) variable stiffness springs

NARCIS (Netherlands)

Carloni, Raffaella; Lapp, Valerie I.; Cremonese, Andrea; Belcari, Juri; Zucchelli, Andrea

This letter presents a novel rotational variable stiffness joint that relies on one motor and a set of variable stiffness springs. The variable stiffness springs are leaf springs with a layered design, i.e., an electro-active layer of electrospun aligned nanofibers of poly(vinylidene

Pharmacological modulation of arterial stiffness.

LENUS (Irish Health Repository)

Boutouyrie, Pierre

2011-09-10

Arterial stiffness has emerged as an important marker of cardiovascular risk in various populations and reflects the cumulative effect of cardiovascular risk factors on large arteries, which in turn is modulated by genetic background. Arterial stiffness is determined by the composition of the arterial wall and the arrangement of these components, and can be studied in humans non-invasively. Age and distending pressure are two major factors influencing large artery stiffness. Change in arterial stiffness with drugs is an important endpoint in clinical trials, although evidence for arterial stiffness as a therapeutic target still needs to be confirmed. Drugs that independently affect arterial stiffness include antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone system, hormone replacement therapy and some antidiabetic drugs such as glitazones. While the quest continues for \\'de-stiffening drugs\\

Measurements of stiff-material compliance on the nanoscale using ultrasonic force microscopy

Science.gov (United States)

Dinelli, F.; Biswas, S. K.; Briggs, G. A. D.; Kolosov, O. V.

2000-05-01

Ultrasonic force microscopy (UFM) was introduced to probe nanoscale mechanical properties of stiff materials. This was achieved by vibrating the sample far above the first resonance of the probing atomic force microscope cantilever where the cantilever becomes dynamically rigid. By operating UFM at different set force values, it is possible to directly measure the absolute values of the tip-surface contact stiffness. From this an evaluation of surface elastic properties can be carried out assuming a suitable solid-solid contact model. In this paper we present curves of stiffness as a function of the normal load in the range of 0-300 nN. The dependence of stiffness on the relative humidity has also been investigated. Materials with different elastic constants (such as sapphire lithium fluoride, and silicon) have been successfully differentiated. Continuum mechanics models cannot however explain the dependence of stiffness on the normal force and on the relative humidity. In this high-frequency regime, it is likely that viscous forces might play an important role modifying the tip-surface interaction. Plastic deformation might also occur due to the high strain rates applied when ultrasonically vibrating the sample. Another possible cause of these discrepancies might be the presence of water in between the two bodies in contact organizing in a solidlike way and partially sustaining the load.

Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy.

Science.gov (United States)

Li, Mi; Liu, LianQing; Xi, Ning; Wang, YueChao; Xiao, XiuBin; Zhang, WeiJing

2015-09-01

Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.

Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

Science.gov (United States)

Lewis, Amanda H; Grandl, Jörg

2015-01-01

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry. Building on this approach, we developed protocols to minimize resting membrane curvature and tension prior to probing Piezo1 activity. We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. Our results explain how Piezo1 can function efficiently and with adaptable sensitivity as a sensor of mechanical stimulation in diverse cellular contexts. DOI: http://dx.doi.org/10.7554/eLife.12088.001 PMID:26646186

Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking

Science.gov (United States)

Takahashi, Kota Z.; Gross, Michael T.; van Werkhoven, Herman; Piazza, Stephen J.; Sawicki, Gregory S.

2016-07-01

Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage.

On the effects of geometry, defects, and material asymmetry on the mechanical response of shape memory alloy cellular lattice structures

International Nuclear Information System (INIS)

Ravari, M R Karamooz; Kadkhodaei, M; Ghaei, A; Esfahani, S Nasr; Andani, M Taheri; Elahinia, M; Karaca, H

2016-01-01

Shape memory alloy (such as NiTi) cellular lattice structures are a new class of advanced materials with many potential applications. The cost of fabrication of these structures however is high. It is therefore necessary to develop modeling methods to predict the functional behavior of these alloys before fabrication. The main aim of the present study is to assess the effects of geometry, microstructural imperfections and material asymmetric response of dense shape memory alloys on the mechanical response of cellular structures. To this end, several cellular and dense NiTi samples are fabricated using a selective laser melting process. Both cellular and dense specimens were tested in compression in order to obtain their stress–strain response. For modeling purposes, a three -dimensional (3D) constitutive model based on microplane theory which is able to describe the material asymmetry was employed. Five finite element models based on unit cell and multi-cell methods were generated to predict the mechanical response of cellular lattices. The results show the considerable effects of the microstructural imperfections on the mechanical response of the cellular lattice structures. The asymmetric material response of the bulk material also affects the mechanical response of the corresponding cellular structure. (paper)

Knee joint laxity and passive stiffness in meniscectomized patients compared with healthy controls.

Science.gov (United States)

Thorlund, Jonas B; Creaby, Mark W; Wrigley, Tim V; Metcalf, Ben R; Bennell, Kim L

2014-10-01

Passive mechanical behavior of the knee in the frontal plane, measured as angular laxity and mechanical stiffness, may play an important role in the pathogenesis of knee osteoarthritis (OA). Little is known about knee laxity and stiffness prior to knee OA onset. We investigated knee joint angular laxity and passive stiffness in meniscectomized patients at high risk of knee OA compared with healthy controls. Sixty patients meniscectomized for a medial meniscal tear (52 men, 41.4 ± 5.5 years, 175.3 ± 7.9 cm, 83.6 ± 12.8 kg, mean ± SD) and 21 healthy controls (18 men, 42.0 ± 6.7 years, 176.8 ± 5.7 cm, 77.8 ± 13.4 kg) had their knee joint angular laxity and passive stiffness assessed twice ~2.3 years apart. Linear regression models including age, sex, height and body mass as covariates in the adjusted model were used to assess differences between groups. Greater knee joint varus (-10.1 vs. -7.3°, pknee joint angular laxity and reduced passive stiffness ~3 months post surgery compared with controls. In addition, the results indicated that knee joint laxity may increase over time in meniscectomized patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Finite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.

Science.gov (United States)

Maquer, Ghislain; Laurent, Marc; Brandejsky, Vaclav; Pretterklieber, Michael L; Zysset, Philippe K

2014-06-01

Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently

Chemo-mechanical control of neural stem cell differentiation

Science.gov (United States)

Geishecker, Emily R.

Cellular processes such as adhesion, proliferation, and differentiation are controlled in part by cell interactions with the microenvironment. Cells can sense and respond to a variety of stimuli, including soluble and insoluble factors (such as proteins and small molecules) and externally applied mechanical stresses. Mechanical properties of the environment, such as substrate stiffness, have also been suggested to play an important role in cell processes. The roles of both biochemical and mechanical signaling in fate modification of stem cells have been explored independently. However, very few studies have been performed to study well-controlled chemo-mechanotransduction. The objective of this work is to design, synthesize, and characterize a chemo-mechanical substrate to encourage neuronal differentiation of C17.2 neural stem cells. In Chapter 2, Polyacrylamide (PA) gels of varying stiffnesses are functionalized with differing amounts of whole collagen to investigate the role of protein concentration in combination with substrate stiffness. As expected, neurons on the softest substrate were more in number and neuronal morphology than those on stiffer substrates. Neurons appeared locally aligned with an expansive network of neurites. Additional experiments would allow for statistical analysis to determine if and how collagen density impacts C17.2 differentiation in combination with substrate stiffness. Due to difficulties associated with whole protein approaches, a similar platform was developed using mixed adhesive peptides, derived from fibronectin and laminin, and is presented in Chapter 3. The matrix elasticity and peptide concentration can be individually modulated to systematically probe the effects of chemo-mechanical signaling on differentiation of C17.2 cells. Polyacrylamide gel stiffness was confirmed using rheological techniques and found to support values published by Yeung et al. [1]. Cellular growth and differentiation were assessed by cell counts

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

Science.gov (United States)

Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Interlocking-induced stiffness in stochastically microcracked materials beyond the transport percolation threshold

Science.gov (United States)

Picu, R. C.; Pal, A.; Lupulescu, M. V.

2016-04-01

We study the mechanical behavior of two-dimensional, stochastically microcracked continua in the range of crack densities close to, and above, the transport percolation threshold. We show that these materials retain stiffness up to crack densities much larger than the transport percolation threshold due to topological interlocking of sample subdomains. Even with a linear constitutive law for the continuum, the mechanical behavior becomes nonlinear in the range of crack densities bounded by the transport and stiffness percolation thresholds. The effect is due to the fractal nature of the fragmentation process and is not linked to the roughness of individual cracks.

Measurement and Treatment of Passive Muscle Stiffness

DEFF Research Database (Denmark)

Kirk, Henrik

, which aimed to investigate: 1) The development of a clinical method to evaluate and distinguish neural (reflex mediated stiffness) and non-neural (passive muscle stiffness) components of muscle stiffness in adults with CP by objective and reliable measurements. 2) The association between increased...... and reliability of the method, and argue for the use of the method in the clinical practice. The device is able to distinguish between passive muscle stiffness and reflex-mediated stiffness in subjects with CP. It shows good high intrarater and interrater reliability in evaluation of passive muscle stiffness...... to measure muscle stiffness, and distinguish between passive muscle stiffness and reflex-mediated stiffness. Furthermore, it is a reliable device to measure changes in passive ROM. Treatment of passive muscle stiffness should be directed towards intense training, comprising many repetitions with a functional...

Estimation of Lamina Stiffness and Strength of Quadriaxial Non-Crimp Fabric Composites Based on Semi-Laminar Considerations

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Yong Cao

2016-09-01

Full Text Available Quadriaxial non-crimp fabric (QNCF composites are increasingly being used as primary structural materials in aircraft and automotive applications. Predicting the mechanical properties of QNCF lamina is more complicated compared with that of unidirectional (UD composites, because of the knitting connection of different plies. In this study, to analyze the stiffness and strength of the QNCF composites, a novel modeling strategy for the meso-scale features is presented based on the semi-laminar assumption. Following the view of the mechanical properties of single composite lamina, the complex QNCF layer is decomposed into individual plies. Three different representative unit cells along fiber direction are selected to predict the mechanical performance of QNCF, including in-plane stiffness, damage initiation, and stiffness degradation. To validate the developed modeling strategy, the predictions are compared with existing experimental results, where a good agreement is presented on the prediction of in-plane stiffness and strength. Furthermore, the effect of in-plane fiber distortion, induced by the stitching yarn on the mechanical properties, is studied.

Human arm stiffness and equilibrium-point trajectory during multi-joint movement.

Science.gov (United States)

Gomi, H; Kawato, M

1997-03-01

By using a newly designed high-performance manipulandum and a new estimation algorithm, we measured human multi-joint arm stiffness parameters during multi-joint point-to-point movements on a horizontal plane. This manipulandum allows us to apply a sufficient perturbation to subject's arm within a brief period during movement. Arm stiffness parameters were reliably estimated using a new algorithm, in which all unknown structural parameters could be estimated independent of arm posture (i.e., constant values under any arm posture). Arm stiffness during transverse movement was considerably greater than that during corresponding posture, but not during a longitudinal movement. Although the ratios of elbow, shoulder, and double-joint stiffness were varied in time, the orientation of stiffness ellipses during the movement did not change much. Equilibrium-point trajectories that were predicted from measured stiffness parameters and actual trajectories were slightly sinusoidally curved in Cartesian space and their velocity profiles were quite different from the velocity profiles of actual hand trajectories. This result contradicts the hypothesis that the brain does not take the dynamics into account in movement control depending on the neuromuscular servo mechanism; rather, it implies that the brain needs to acquire some internal models of controlled objects.

On gear tooth stiffness evaluation

DEFF Research Database (Denmark)

Pedersen, Niels Leergaard; Jørgensen, Martin Felix

2014-01-01

The estimation of gear stiffness is important for determining the load distribution between the gear teeth when two sets of teeth are in contact. Two factors have a major influence on the stiffness; firstly the boundary condition through the gear rim size included in the stiffness calculation...

Impact of matrix stiffness on fibroblast function

Energy Technology Data Exchange (ETDEWEB)

El-Mohri, Hichem; Wu, Yang; Mohanty, Swetaparna; Ghosh, Gargi, E-mail: gargi@umich.edu

2017-05-01

Chronic non-healing wounds, caused by impaired production of growth factors and reduced vascularization, represent a significant burden to patients, health care professionals, and health care system. While several wound dressing biomaterials have been developed, the impact of the mechanical properties of the dressings on the residing cells and consequently on the healing of the wounds is largely overlooked. The primary focus of this study is to explore whether manipulation of the substrate mechanics can regulate the function of fibroblasts, particularly in the context of their angiogenic activity. A photocrosslinkable hydrogel platform with orthogonal control over gel modulus and cell adhesive sites was developed to explore the quantitative relationship between ECM compliance and fibroblast function. Increase in matrix stiffness resulted in enhanced fibroblast proliferation and stress fiber formation. However, the angiogenic activity of fibroblasts was found to be optimum when the cells were seeded on compliant matrices. Thus, the observations suggest that the stiffness of the wound dressing material may play an important role in the progression of wound healing. - Highlights: • Proliferation and stress fiber formation of fibroblasts increase with increasing matrix mechanics. • Cell area correlates with the growth of fibroblasts. • Angiogenic activity of fibroblasts optimum when cells seeded on compliant gels.

The Role of Mechanical Force in Molecular and Cellular during Orthodontic Tooth Movement

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Ida Bagus Narmada

2012-10-01

Full Text Available Application of mechanical force on abnormally positioned tooth, cause changes in tooth location and transmitted to the bone ia the periodontal ligament (PDL produce orthodontic tooth movement. This force application is further way that remodeling in the area occurs. In order to develop biological strategies for enhancing this movement of teeth in bone, the underlying mechanisms of bone resorption and apposition should be understood in detail. Analysis of gingival crevicular fluid (GCF may be a good means of examining the on going molecular and cellular process associated with gingival and bone turnover during orthodontic tooth movement. If it could be possible to biologically monitor and predict the outcome of orthodontic force, then the appliance management could be based on dividual tissue response and the effectiveness of the treatment could be improved and understanding their biology is critical to finding ways to modify bone biology to move teeth faster. The present article reviewed a short introduction to some mayors advanced mechanical force in molecular and cellular biology during orthodontic tooth movement.DOI: 10.14693/jdi.v15i3.30

Dynamic stiffness of suction caissons

DEFF Research Database (Denmark)

Ibsen, Lars Bo; Liingaard, Morten; Andersen, Lars

The purpose of this report is to evaluate the dynamic soil-structure interaction of suction caissons for offshore wind turbines. The investigation is limited to a determination of the vertical dynamic stiffness of suction caissons. The soil surrounding the foundation is homogenous with linear...... viscoelastic properties. The dynamic stiffness of the suction caisson is expressed by dimensionless frequency-dependent dynamic stiffness coefficients corresponding to the vertical degree of freedom. The dynamic stiffness coefficients for the foundations are evaluated by means of a dynamic three...

The biocompatibility of fluorescent nanodiamonds and their mechanism of cellular uptake

International Nuclear Information System (INIS)

Vaijayanthimala, Vairakkannu; Tzeng, Yan-Kai; Chang, Huan-Cheng; Li, Chung-Leung

2009-01-01

The labeling of cells with fluorescent nanoparticles is promising for various biomedical applications. The objective of this study is to evaluate the biocompatibility and the mechanism of the cellular uptake of fluorescent nanodiamonds (FNDs) in cancer cells (HeLa) and pre-adipocytes (3T3-L1). With flow cytometry and the use of a battery of metabolic and cytoskeletal inhibitors, we found that the mechanism of the FND uptake in both cells is by energy-dependent clathrin-mediated endocytosis. In addition, the surface charge of FND influences its cellular uptake, as the uptake of poly-L-lysine-coated FNDs is better than that of oxidative-acid-purified FNDs at the same concentration in regular medium with or without serum. We also confirm that the proliferative potential of FND-treated and untreated cells does not exhibit any significant differences when measured at bulk cultures, and more stringently at clonal cell density. Further biocompatibility studies indicate that the in vitro differentiation of 3T3-L1 pre-adipocytes and 489-2 osteoprogenitors is not affected by the FND treatment. Our results show that FNDs are biocompatible and ideal candidates for potential applications in human stem cell research.

The biocompatibility of fluorescent nanodiamonds and their mechanism of cellular uptake

Energy Technology Data Exchange (ETDEWEB)

Vaijayanthimala, Vairakkannu; Tzeng, Yan-Kai; Chang, Huan-Cheng [Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan (China); Li, Chung-Leung, E-mail: hcchang@po.sinica.edu.t, E-mail: chungL@gate.sinica.edu.t [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China)

2009-10-21

The labeling of cells with fluorescent nanoparticles is promising for various biomedical applications. The objective of this study is to evaluate the biocompatibility and the mechanism of the cellular uptake of fluorescent nanodiamonds (FNDs) in cancer cells (HeLa) and pre-adipocytes (3T3-L1). With flow cytometry and the use of a battery of metabolic and cytoskeletal inhibitors, we found that the mechanism of the FND uptake in both cells is by energy-dependent clathrin-mediated endocytosis. In addition, the surface charge of FND influences its cellular uptake, as the uptake of poly-L-lysine-coated FNDs is better than that of oxidative-acid-purified FNDs at the same concentration in regular medium with or without serum. We also confirm that the proliferative potential of FND-treated and untreated cells does not exhibit any significant differences when measured at bulk cultures, and more stringently at clonal cell density. Further biocompatibility studies indicate that the in vitro differentiation of 3T3-L1 pre-adipocytes and 489-2 osteoprogenitors is not affected by the FND treatment. Our results show that FNDs are biocompatible and ideal candidates for potential applications in human stem cell research.

Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

Science.gov (United States)

Della Corte, Vittoriano; Tuttolomondo, Antonino; Pecoraro, Rosaria; Di Raimondo, Domenico; Vassallo, Valerio; Pinto, Antonio

2016-01-01

In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to

Effect of crosslink torsional stiffness on elastic behavior of semiflexible polymer networks

Science.gov (United States)

Hatami-Marbini, H.

2018-02-01

Networks of semiflexible filaments are building blocks of different biological and structural materials such as cytoskeleton and extracellular matrix. The mechanical response of these systems when subjected to an applied strain at zero temperature is often investigated numerically using networks composed of filaments, which are either rigidly welded or pinned together at their crosslinks. In the latter, filaments during deformation are free to rotate about their crosslinks while the relative angles between filaments remain constant in the former. The behavior of crosslinks in actual semiflexible networks is different than these idealized models and there exists only partial constraint on torques at crosslinks. The present work develops a numerical model in which two intersecting filaments are connected to each other by torsional springs with arbitrary stiffness. We show that fiber networks composed of rigid and freely rotating crosslinks are the limiting case of the present model. Furthermore, we characterize the effects of stiffness of crosslinks on effective Young's modulus of semiflexible networks as a function of filament flexibility and crosslink density. The effective Young's modulus is determined as a function of the mechanical properties of crosslinks and is found to vanish for networks composed of very weak torsional springs. Independent of the stiffness of crosslinks, it is found that the effective Young's modulus is a function of fiber flexibility and crosslink density. In low density networks, filaments primarily bend and the effective Young's modulus is much lower than the affine estimate. With increasing filament bending stiffness and/or crosslink density, the mechanical behavior of the networks becomes more affine and the stretching of filaments depicts itself as the dominant mode of deformation. The torsional stiffness of the crosslinks significantly affects the effective Young's modulus of the semiflexible random fiber networks.

A simple indentation device for measuring micrometer-scale tissue stiffness

Energy Technology Data Exchange (ETDEWEB)

Levental, I; Levental, K R; Janmey, P A [Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104 (United States); Klein, E A; Assoian, R [Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Miller, R T [Departments of Medicine and Physiology, Louis Stokes VAMC, Cleveland, OH (United States); Wells, R G, E-mail: janmey@mail.med.upenn.ed [Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States)

2010-05-19

Mechanical properties of cells and extracellular matrices are critical determinants of function in contexts including oncogenic transformation, neuronal synapse formation, hepatic fibrosis and stem cell differentiation. The size and heterogeneity of biological specimens and the importance of measuring their mechanical properties under conditions that resemble their environments in vivo present a challenge for quantitative measurement. Centimeter-scale tissue samples can be measured by commercial instruments, whereas properties at the subcellular (nm) scale are accessible by atomic force microscopy, optical trapping, or magnetic bead microrheometry; however many tissues are heterogeneous on a length scale between micrometers and millimeters which is not accessible to most current instrumentation. The device described here combines two commercially available technologies, a micronewton resolution force probe and a micromanipulator for probing soft biological samples at sub-millimeter spatial resolution. Several applications of the device are described. These include the first measurement of the stiffness of an intact, isolated mouse glomerulus, quantification of the inner wall stiffness of healthy and diseased mouse aortas, and evaluation of the lateral heterogeneity in the stiffness of mouse mammary glands and rat livers with correlation of this heterogeneity with malignant or fibrotic pathology as evaluated by histology.

Sex Differences in Limb and Joint Stiffness in Recreational Runners

Directory of Open Access Journals (Sweden)

Sinclair Jonathan

2015-09-01

Full Text Available Purpose. Female runners are known to be at greater risk from chronic running injuries than age-matched males, although the exact mechanisms are often poorly understood. The aim of the current investigation was to determine if female recreational runners exhibit distinct limb and joint stiffness characteristics in relation to their male counterparts. Methods. Fourteen male and fourteen female runners ran over a force platform at 4.0 m · s-1. Lower limb kinematics were collected using an eight-camera optoelectric motion capture system operating at 250 Hz. Measures of limb and joint stiffness were calculated as a function of limb length and joint moments divided by the extent of limb and joint excursion. All stiffness and joint moment parameters were normalized to body mass. Sex differences in normalized limb and knee and ankle joint stiffness were examined statistically using independent samples t tests. Results. The results indicate that normalized limb (male = 0.18 ± 0.07, female = 0.37 ± 0.10 kN · kg · m-1 and knee stiffness (male = 5.59 ± 2.02, female = 7.34 ± 1.78 Nm · kg · rad-1 were significantly greater in female runners. Conclusions. On the basis that normalized knee and limb stiffness were shown to be significantly greater in female runners, the findings from the current investigation may provide further insight into the aetiology of the distinct injury patterns observed between sexes.

Determination of rolling resistance coefficient based on normal tyre stiffness

Science.gov (United States)

Rykov, S. P.; Tarasuyk, V. N.; Koval, V. S.; Ovchinnikova, N. I.; Fedotov, A. I.; Fedotov, K. V.

2018-03-01

The purpose of the article is to develop analytical dependence of wheel rolling resistance coefficient based on the mathematical description of normal tyre stiffness. The article uses the methods of non-holonomic mechanics and plane section methods. The article shows that the abscissa of gravity center of tyre stiffness expansion by the length of the contact area is the shift of normal road response. It can be used for determining rolling resistance coefficient. When determining rolling resistance coefficient using ellipsis and power function equations, one can reduce labor costs for testing and increase assessment accuracy.

Water retention properties of stiff silt

Directory of Open Access Journals (Sweden)

Barbara Likar

2017-06-01

Full Text Available Recent research into the behaviour of soils has shown that it is in fact much more complex than can be described by the mechanics of saturated soils. Nowadays the trend of investigations has shifted towards the unsaturated state. Despite the signifiant progress that has been made so far, there are still a lot of unanswered questions related to the behaviour of unsaturated soils. For this reason, in the fild of geotechnics some new concepts are developed, which include the study of soil suction. Most research into soil suction has involved clayey and silty material, whereas up until recently no data have been available about measurements in very stiff preconsolidated sandy silt. Very stiff preconsolidated sandy silt is typical of the Krško Basin, where it is planned that some very important geotechnical structures will be built, so that knowledge about the behaviour of such soils at increased or decreased water content is essential. Several different methods can be used for soil suction measurements. In the paper the results of measurements carried out on very stiff preconsolidated sandy silt in a Bishop - Wesley double-walled triaxial cell are presented and compared with the results of soil suction measurements performed by means of a potentiometer (WP4C. All the measurement results were evaluated taking into account already known results given in the literature, using the three most commonly used mathematical models. Until now a lot of papers dealing with suction measurements in normal consolidated and preconsolidated clay have been published. Measurements on very stiff preconsolidated sandy silt, as presented in this paper were not supported before.

Interaction of the human body and surfaces of different stiffness during drop jumps.

Science.gov (United States)

Arampatzis, Adamantios; Stafilidis, Savvas; Morey-Klapsing, Gaspar; Brüggemann, Gert-peter

2004-03-01

The purpose of this study was to examine two hypotheses: (a) the stiffness of the surface influences the leg stiffness of the subjects during drop jumps, and (b) drop jumping performance (jumping height and energy rates of the subject's center of mass during the contact phase) increases when decreasing surface stiffness due to a greater energy storage capacity of the surface for a given acting force. Ten female subjects performed a series of drop jumps from 40-cm height onto two sprung surfaces with different stiffness. Those trials of each subject displaying the maximal mechanical power during the upward phase were analyzed. The ground reaction forces were measured using a force plate. Sagittal kinematics of the subject's body positions and the deformation of the surface were recorded using two high-speed video cameras. On the soft surface, the jumping height and the energy rates of the subjects during the contact phase were greater than on the hard one. The energy delivered by the subjects during the upward phase, the leg and joint stiffness, as well as the range of motion of the subjects remained unchanged for both surfaces. The absolute energy loss is lower for the hard surface, but the jumping performance is greater for the soft one. The reason is a higher ratio of positive to negative mechanical work done by the subjects during the contact phase. The adjustment of the subjects to different surfaces is not only dependent on the stiffness of the surface but also on the intensity of the movement.

Sensitivity analysis on the effective stiffness properties of 3-D orthotropic honeycomb cores

Science.gov (United States)

Karakoç, Alp

2018-01-01

The present study investigates the influences of representative volume element RVE mesh and material parameters, here cell wall elastic moduli, on the effective stiffness properties of three dimensional orthotropic honeycomb cores through strain driven computational homogenization in the finite element framework. For this purpose, case studies were carried out, for which hexagonal cellular RVEs were generated, meshed with eight node linear brick finite elements of varying numbers. Periodic boundary conditions were then implemented on the RVE boundaries by using one-to-one nodal match for the corresponding corners, edges and surfaces for the imposed macroscopic strains. As a novelty, orthotropic material properties were assigned for each cell wall by means of the transformation matrices following the cell wall orientations. Thereafter, simulations were conducted and volume averaged macroscopic stresses were obtained. Eventually, effective stiffness properties were obtained, through which RVE sensitivity analysis was carried out. The investigations indicate that there is a strong relation between number of finite elements and most of the effective stiffness parameters. In addition to this, cell wall elastic moduli also play critical role on the effective properties of the investigated materials.

Comparative study on stiffness properties of WOODCAST and conventional casting materials.

Science.gov (United States)

Pirhonen, Eija; Pärssinen, Antti; Pelto, Mika

2013-08-01

Plaster-of-Paris and synthetic materials (e.g. fibreglass) have been in clinical use as casting materials for decades. An innovative casting material, WOODCAST, brings interesting alternatives to the traditional materials. The aim of this study was to compare the stiffness properties of the WOODCAST material to traditional casting materials. In immobilization by casting, materials with variable stiffness properties are required. Ring stiffness of cylindrical samples correlates well with cast rigidity. For load-bearing structures, the use of the WOODCAST Splint is recommended as equally high stiffness was obtained with the WOODCAST Splint as was with fibreglass. The WOODCAST 2 mm product is optimal for structures where some elasticity is required, and WOODCAST Ribbon can be used in any WOODCAST structure where further reinforcement is needed. The results show that WOODCAST material can be used in replacing traditional casting materials used in extremity immobilization. The mechanical properties of casting material play an important role in safe and effective fracture immobilization. Stiffness properties of the WOODCAST casting material and conventional materials - fibreglass and plaster-of-Paris - were analysed in this study. The WOODCAST Splint appears to compare favorably with traditional materials such as Scotchcast.

A quantitative method for evaluating inferior glenohumeral joint stiffness using ultrasonography.

Science.gov (United States)

Tsai, Wen-Wei; Lee, Ming-Yih; Yeh, Wen-Lin; Cheng, Shih-Chung; Soon, Kok-Soon; Lei, Kin Fong; Lin, Wen-Yen

2013-02-01

Subluxation of the affected shoulder in post-stroke patients is associated with nerve disorders and muscle fatigue. Clinicians must be able to accurately and reliably measure inferior glenohumeral subluxation in patients to provide appropriate treatment. However, quantitative methods for evaluating the laxity and stiffness of the glenohumeral joint (GHJ) are still being developed. The aim of this study was to develop a new protocol for evaluating the laxity and stiffness of the inferior GHJ using ultrasonography under optimal testing conditions and to investigate changes in the GHJ from a commercially available humerus brace and shoulder brace. Multistage inferior displacement forces were applied to create a glide between the most cephalad point on the visible anterosuperior surface of the humeral head and coracoid process in seven healthy volunteers. GHJ stiffness was defined as the slope of the linear regression line between the glides and different testing loads. The testing conditions were defined by different test loading mechanisms (n=2), shoulder constraining conditions (n=2), and loading modes (n=4). The optimal testing condition was defined as the condition with the least residual variance of measured laxity to the calculated stiffness under different testing loads. A paired t-test was used to compare the laxity and stiffness of the inferior GHJ using different braces. No significant difference was identified between the two test loading mechanisms (t=0.218, p=0.831) and two shoulder constraining conditions (t=-0.235, p=0.818). We concluded that ultrasonographic laxity measurements performed using a pulley set loading mechanism was as reliable as direct loading. Additionally, constraining the unloaded shoulder was proposed due to the lower mean residual variance value. Moreover, pulling the elbow downward with loading on the upper arm was suggested, as pulling the elbow downward with the elbow flexed and loading on the forearm may overestimate stiffness

The agglomeration state of nanoparticles can influence the mechanism of their cellular internalisation.

Science.gov (United States)

Halamoda-Kenzaoui, Blanka; Ceridono, Mara; Urbán, Patricia; Bogni, Alessia; Ponti, Jessica; Gioria, Sabrina; Kinsner-Ovaskainen, Agnieszka

2017-06-26

Significant progress of nanotechnology, including in particular biomedical and pharmaceutical applications, has resulted in a high number of studies describing the biological effects of nanomaterials. Moreover, a determination of so-called "critical quality attributes", that is specific physicochemical properties of nanomaterials triggering the observed biological response, has been recognised as crucial for the evaluation and design of novel safe and efficacious therapeutics. In the context of in vitro studies, a thorough physicochemical characterisation of nanoparticles (NPs), also in the biological medium, is necessary to allow a correlation with a cellular response. Following this concept, we examined whether the main and frequently reported characteristics of NPs such as size and the agglomeration state can influence the level and the mechanism of NP cellular internalization. We employed fluorescently-labelled 30 and 80 nm silicon dioxide NPs, both in agglomerated and non-agglomerated form. Using flow cytometry, transmission electron microscopy, the inhibitors of endocytosis and gene silencing we determined the most probable routes of cellular uptake for each form of tested silica NPs. We observed differences in cellular uptake depending on the size and the agglomeration state of NPs. Caveolae-mediated endocytosis was implicated particularly in the internalisation of well dispersed silica NPs but with an increase of the agglomeration state of NPs a combination of endocytic pathways with a predominant role of macropinocytosis was noted. We demonstrated that the agglomeration state of NPs is an important factor influencing the level of cell uptake and the mechanism of endocytosis of silica NPs.

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching.

Science.gov (United States)

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged.

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching

Science.gov (United States)

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R.; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged. PMID:27119147

Excitation of large-amplitude parametric resonance by the mechanical stiffness modulation of a microstructure

International Nuclear Information System (INIS)

Krylov, Slava; Gerson, Yuval; Nachmias, Tali; Keren, Uri

2010-01-01

In this work we report on an approach allowing efficient parametric excitation of large-amplitude stable oscillations of a microstructure operated by a parallel-plate electrode, and present results of a theoretical and experimental investigation of the device. The frame-type structure, fabricated from a silicon on insulator (SOI) substrate using deep reactive ion etching (DRIE), consists a pair of cantilever-type suspensions connected at their ends by a link. The time-varying electrostatic force applied to the link by a parallel-plate electrode is transformed into a periodic tension of the beams, resulting in the modulation of their flexural stiffness and consequently the mechanical parametric excitation of the structure. The lateral compliance of the beams allows for large-amplitude in-plane oscillations in the direction parallel to the electrode while high axial stiffness prevents undesirable instabilities. The lumped model of the device, considered as an assembly of geometrically nonlinear massless flexures and a rigid massive link and built using the Rayleigh–Ritz method, predicted the feasibility of the excitation approach. The fabricated devices were operated in ambient air conditions by a combination of a steady (dc) and time-dependent (ac) components of voltage and the large-amplitude responses, up to 75 µm, in the vicinity of the principal parametric and primary resonances were registered by means of video acquisition and image processing. The shapes of the experimental resonant curves were consistent with those predicted by the model. The location and size of the instability regions on the frequency–voltage plane (parametric tongues) were quantitatively in good agrement with the model results. Theoretical and experimental results indicate that the suggested approach can be efficiently used for excitation of various types of microdevices where stable resonant operation combined with robustness and large vibrational amplitudes are desirable

Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities.

Science.gov (United States)

Gajarsa, Jason J; Kloner, Robert A

2011-01-01

As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed "remodeling." This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin-angiotensin-aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.

LSODE, 1. Order Stiff or Non-Stiff Ordinary Differential Equations System Initial Value Problems

International Nuclear Information System (INIS)

Hindmarsh, A.C.; Petzold, L.R.

2005-01-01

1 - Description of program or function: LSODE (Livermore Solver for Ordinary Differential Equations) solves stiff and non-stiff systems of the form dy/dt = f. In the stiff case, it treats the Jacobian matrix df/dy as either a dense (full) or a banded matrix, and as either user-supplied or internally approximated by difference quotients. It uses Adams methods (predictor-corrector) in the non-stiff case, and Backward Differentiation Formula (BDF) methods (the Gear methods) in the stiff case. The linear systems that arise are solved by direct methods (LU factor/solve). The LSODE source is commented extensively to facilitate modification. Both a single-precision version and a double-precision version are available. 2 - Methods: It is assumed that the ODEs are given explicitly, so that the system can be written in the form dy/dt = f(t,y), where y is the vector of dependent variables, and t is the independent variable. LSODE contains two variable-order, variable- step (with interpolatory step-changing) integration methods. The first is the implicit Adams or non-stiff method, of orders one through twelve. The second is the backward differentiation or stiff method (or BDF method, or Gear's method), of orders one through five. 3 - Restrictions on the complexity of the problem: The differential equations must be given in explicit form, i.e., dy/dt = f(y,t). Problems with intermittent high-speed transients may cause inefficient or unstable performance

Stiffness Control of Variable Serial Elastic Actuators: Energy Efficiency through Exploitation of Natural Dynamics

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Philipp Beckerle

2017-09-01

Full Text Available Variable elastic actuators are very promising for applications in physical human–robot interaction. Besides enabling human safety, such actuators can support energy efficiency, especially if the natural behavior of the system is exploited. In this paper, the power and energy consumption of variable stiffness actuators with serial elasticity is investigated analytically and experimentally. Besides the fundamental mechanics, the influence of friction and electrical losses is discussed. A simple but effective stiffness control method is used to exploit the corresponding knowledge of natural dynamics by tuning the system to antiresonance operation. Despite nonlinear friction effects and additional electrical dynamics, the consideration of the ideal mechanical dynamics is completely sufficient for stiffness control. Simulations and experiments show that this yields a distinct reduction in power and energy consumption, which underlines the suitability of the control strategy.

Properties and determination of the interface stiffness

International Nuclear Information System (INIS)

Du Danxu; Zhang Hao; Srolovitz, David J.

2007-01-01

The chemical potential of a curved interface contains a term that is proportional to the product of the interface curvature and the interface stiffness. In crystalline materials, the interface stiffness is a tensor. This paper examines several basic issues related to the properties of the interface stiffness, especially the determination of the interface stiffness in particular directions (i.e. the commonly used scalar form of the interface stiffness). Of the five parameters that describe an arbitrary grain boundary, only those describing the inclination are crucial for the scalar stiffness. We also examine the influence of crystal symmetry on the stiffness tensor for both free surfaces and grain boundaries. This results in substantial simplifications for cases in which interfaces possess mirror or rotational symmetries. An efficient method for determining the interface stiffness tensor using atomistic simulations is proposed

Mechanical analysis of single myocyte contraction in a 3-D elastic matrix.

Directory of Open Access Journals (Sweden)

John Shaw

Full Text Available Cardiac myocytes experience mechanical stress during each heartbeat. Excessive mechanical stresses under pathological conditions cause functional and structural remodeling that lead to heart diseases, yet the precise mechanisms are still incompletely understood. To study the cellular and molecular level mechanotransduction mechanisms, we developed a new 'cell-in-gel' experimental system to exert multiaxial (3-D stresses on a single myocyte during active contraction.Isolated myocytes are embedded in an elastic hydrogel to simulate the mechanical environment in myocardium (afterload. When electrically stimulated, the in-gel myocyte contracts while the matrix resists shortening and broadening of the cell, exerting normal and shear stresses on the cell. Here we provide a mechanical analysis, based on the Eshelby inclusion problem, of the 3-D strain and stress inside and outside the single myocyte during contraction in an elastic matrix.(1 The fractional shortening of the myocyte depends on the cell's geometric dimensions and the relative stiffness of the cell to the gel. A slender or softer cell has less fractional shortening. A myocyte of typical dimensions embedded in a gel of similar elastic stiffness can contract only 20% of its load-free value. (2 The longitudinal stress inside the cell is about 15 times the transverse stress level. (3 The traction on the cell surface is highly non-uniform, with a maximum near its ends, showing 'hot spots' at the location of intercalated disks. (4 The mechanical energy expenditure of the myocyte increases with the matrix stiffness in a monotonic and nonlinear manner.Our mechanical analyses provide analytic solutions that readily lend themselves to parametric studies. The resulting 3-D mapping of the strain and stress states serve to analyze and interpret ongoing cell-in-gel experiments, and the mathematical model provides an essential tool to decipher and quantify mechanotransduction mechanisms in cardiac

Elastic stiffnesses of an Nb-Ti/Cu-composite superconductive wire

Science.gov (United States)

Kim, Sudook; Ledbetter, Hassel; Ogi, Hirotsugu

2000-09-01

Elastic-stiffness coefficients were determined on a 1.4-mm-diameter wire consisting of superconducting Nb-Ti fibers in a copper matrix, with a polyvinyl-resin coating. The matrix contained 324 Nb-Ti fibers. An electromagnetic-acoustic-resonance method was used to obtain five independent elastic-stiffness coefficients assuming transverse-isotropic symmetry. From these we calculated Young moduli, bulk modulus, and principal Poisson ratios. As a check, we used a mechanical-impulse-excitation method to directly measure the Young modulus in the fiber direction. The three-phase composite wire showed a 10% anisotropy in the Young modulus.

Stiffness of desiccating insect wings

International Nuclear Information System (INIS)

Mengesha, T E; Vallance, R R; Mittal, R

2011-01-01

The stiffness of insect wings is typically determined through experimental measurements. Such experiments are performed on wings removed from insects. However, the wings are subject to desiccation which typically leads to an increase in their stiffness. Although this effect of desiccation is well known, a comprehensive study of the rate of change in stiffness of desiccating insect wings would be a significant aid in planning experiments as well as interpreting data from such experiments. This communication presents a comprehensive experimental analysis of the change in mass and stiffness of gradually desiccating forewings of Painted Lady butterflies (Vanessa cardui). Mass and stiffness of the forewings of five butterflies were simultaneously measured every 10 min over a 24 h period. The averaged results show that wing mass declined exponentially by 21.1% over this time period with a time constant of 9.8 h, while wing stiffness increased linearly by 46.2% at a rate of 23.4 μN mm -1 h -1 . For the forewings of a single butterfly, the experiment was performed over a period of 1 week, and the results show that wing mass declined exponentially by 52.2% with a time constant of 30.2 h until it reached a steady-state level of 2.00 mg, while wing stiffness increased exponentially by 90.7% until it reached a steady-state level of 1.70 mN mm -1 . (communication)

Stiffness of desiccating insect wings

Energy Technology Data Exchange (ETDEWEB)

Mengesha, T E; Vallance, R R [Department of Mechanical Engineering, The George Washington University, 738 Phillips Hall, 801 22nd St NW, Washington, DC 20052 (United States); Mittal, R, E-mail: vallance@gwu.edu [Department of Mechanical Engineering, Johns Hopkins University, 126 Latrobe Hall, 3400 N Charles Street, Baltimore, MD 21218 (United States)

2011-03-15

The stiffness of insect wings is typically determined through experimental measurements. Such experiments are performed on wings removed from insects. However, the wings are subject to desiccation which typically leads to an increase in their stiffness. Although this effect of desiccation is well known, a comprehensive study of the rate of change in stiffness of desiccating insect wings would be a significant aid in planning experiments as well as interpreting data from such experiments. This communication presents a comprehensive experimental analysis of the change in mass and stiffness of gradually desiccating forewings of Painted Lady butterflies (Vanessa cardui). Mass and stiffness of the forewings of five butterflies were simultaneously measured every 10 min over a 24 h period. The averaged results show that wing mass declined exponentially by 21.1% over this time period with a time constant of 9.8 h, while wing stiffness increased linearly by 46.2% at a rate of 23.4 {mu}N mm{sup -1} h{sup -1}. For the forewings of a single butterfly, the experiment was performed over a period of 1 week, and the results show that wing mass declined exponentially by 52.2% with a time constant of 30.2 h until it reached a steady-state level of 2.00 mg, while wing stiffness increased exponentially by 90.7% until it reached a steady-state level of 1.70 mN mm{sup -1}. (communication)

Strong, tough and stiff bioinspired ceramics from brittle constituents

Science.gov (United States)

Bouville, Florian; Maire, Eric; Meille, Sylvain; van de Moortèle, Bertrand; Stevenson, Adam J.; Deville, Sylvain

2014-05-01

High strength and high toughness are usually mutually exclusive in engineering materials. In ceramics, improving toughness usually relies on the introduction of a metallic or polymeric ductile phase, but this decreases the material’s strength and stiffness as well as its high-temperature stability. Although natural materials that are both strong and tough rely on a combination of mechanisms operating at different length scales, the relevant structures have been extremely difficult to replicate. Here, we report a bioinspired approach based on widespread ceramic processing techniques for the fabrication of bulk ceramics without a ductile phase and with a unique combination of high strength (470 MPa), high toughness (22 MPa m1/2), and high stiffness (290 GPa). Because only mineral constituents are needed, these ceramics retain their mechanical properties at high temperatures (600 °C). Our bioinspired, material-independent approach should find uses in the design and processing of materials for structural, transportation and energy-related applications.

DMPD: Anti-inflammatory actions of PPAR ligands: new insights on cellular andmolecular mechanisms. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17981503 Anti-inflammatory actions of PPAR ligands: new insights on cellular andmol...) (.html) (.csml) Show Anti-inflammatory actions of PPAR ligands: new insights on cellular andmolecular mech...anisms. PubmedID 17981503 Title Anti-inflammatory actions of PPAR ligands: new insight

Cellular and molecular investigations of the adhesion and mechanics of Listeria monocytogenes

Science.gov (United States)

Eskhan, Asma Omar

Atomic force microscopy has been used to quantify the adherence and mechanical properties of an array of L. monocytogenes strains and their surface biopolymers. First, eight L. monocytogenes strains that represented the two major lineages of the species were compared for their adherence and mechanics at cellular and molecular levels. Our results indicated that strains of lineage' II were characterized by higher adhesion and Young's moduli, longer and more rigid surface biopolymers and lower specific and nonspecific forces when compared to lineage' I strains. Additionally, adherence and mechanical properties of eight L. monocytogenes epidemic and environmental strains were probed. Our results pointed to that environmental and epidemic strains representative of a given lineage were similar in their adherence and mechanical properties when investigated at a cellular level. However, when the molecular properties of the strains were considered, epidemic strains were characterized by higher specific and nonspecific forces, shorter, denser and more flexible biopolymers compared to environmental strains. Second, the role of environmental pH conditions of growth on the adhesion and mechanics of a pathogenic L. monocytogenes EGDe was investigated. Our results pointed to a transition in the adhesion energies for cells cultured at pH 7. In addition, when the types of molecular forces that govern the adhesion were quantified using Poisson statistical approach and using a new proposed method, specific hydrogen-bond energies dominated the bacterial adhesion process. Such a finding is instrumental to researchers designing methods to control bacterial adhesion. Similarly, bacterial cells underwent a transition in their mechanical properties. We have shown that cells cultured at pH 7 were the most rigid compared to those cultured in lower or higher pH conditions of growth. Due to transitions observed in adherence and mechanics when cells were cultured at pH 7, we hypothesized that

Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

International Nuclear Information System (INIS)

Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

1981-01-01

High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

Contact stiffness considerations when simulating tyre/road noise

Science.gov (United States)

Winroth, Julia; Kropp, Wolfgang; Hoever, Carsten; Höstmad, Patrik

2017-11-01

Tyre/road simulation tools that can capture tyre vibrations, rolling resistance and noise generation are useful for understanding the complex processes that are involved and thereby promoting further development and optimisation. The most detailed tyre/road contact models use a spatial discretisation of the contact and assume an interfacial stiffness to account for the small-scale roughness within the elements. This interfacial stiffness has been found to have a significant impact on the simulated noise emissions but no thorough investigations of this sensitivity have been conducted. Three mechanisms are thought to be involved: The horn effect, the modal composition of the vibrational field of the tyre and the contact forces exciting the tyre vibrations. This study used a numerical tyre/road noise simulation tool based on physical relations to investigate these aspects. The model includes a detailed time-domain contact model with linear or non-linear contact springs that accounts for the effect of local tread deformation on smaller length scales. Results confirm that an increase in contact spring stiffness causes a significant increase of the simulated tyre/road noise. This is primarily caused by a corresponding increase in the contact forces, resulting in larger vibrational amplitudes. The horn effect and the modal composition are relatively unaffected and have minor effects on the radiated noise. A more detailed non-linear contact spring formulation with lower stiffness at small indentations results in a reduced high-frequency content in the contact forces and the simulated noise.

Shoulder Stiffness : Current Concepts and Concerns

NARCIS (Netherlands)

Itoi, Eiji; Arce, Guillermo; Bain, Gregory I.; Diercks, Ronald L.; Guttmann, Dan; Imhoff, Andreas B.; Mazzocca, Augustus D.; Sugaya, Hiroyuki; Yoo, Yon-Sik

Shoulder stiffness can be caused by various etiologies such as immobilization, trauma, or surgical interventions. The Upper Extremity Committee of ISAKOS defined the term "frozen shoulder" as idiopathic stiff shoulder, that is, without a known cause. Secondary stiff shoulder is a term that should be

The VSPA Foot: A Quasi-Passive Ankle-Foot Prosthesis With Continuously Variable Stiffness.

Science.gov (United States)

Shepherd, Max K; Rouse, Elliott J

2017-12-01

Most commercially available prosthetic feet do not exhibit a biomimetic torque-angle relationship, and are unable to modulate their mechanics to assist with other mobility tasks, such as stairs and ramps. In this paper, we present a quasi-passive ankle-foot prosthesis with a customizable torque-angle curve and an ability to quickly modulate ankle stiffness between tasks. The customizable torque-angle curve is obtained with a cam-based transmission and a fiberglass leaf spring. To achieve variable stiffness, the leaf spring's support conditions can be actively modulated by a small motor, shifting the torque-angle curve to be more or less stiff. We introduce the design, characterize the available torque-angle curves, and present kinematics from a transtibial amputee subject performing level-ground walking, stair ascent/descent, and ramp ascent/descent. The subject exhibited a more normative range of motion on stairs and ramps at lower stiffness levels, and preferred different stiffness levels for each task. Paired with an appropriate intent recognition system, our novel ankle prosthesis could improve gait biomechanics during walking and many other mobility tasks.

3D Scaffolds with Different Stiffness but the Same Microstructure for Bone Tissue Engineering.

Science.gov (United States)

Chen, Guobao; Dong, Chanjuan; Yang, Li; Lv, Yonggang

2015-07-29

A growing body of evidence has shown that extracellular matrix (ECM) stiffness can modulate stem cell adhesion, proliferation, migration, differentiation, and signaling. Stem cells can feel and respond sensitively to the mechanical microenvironment of the ECM. However, most studies have focused on classical two-dimensional (2D) or quasi-three-dimensional environments, which cannot represent the real situation in vivo. Furthermore, most of the current methods used to generate different mechanical properties invariably change the fundamental structural properties of the scaffolds (such as morphology, porosity, pore size, and pore interconnectivity). In this study, we have developed novel three-dimensional (3D) scaffolds with different degrees of stiffness but the same 3D microstructure that was maintained by using decellularized cancellous bone. Mixtures of collagen and hydroxyapatite [HA: Ca10(PO4)6(OH)2] with different proportions were coated on decellularized cancellous bone to vary the stiffness (local stiffness, 13.00 ± 5.55 kPa, 13.87 ± 1.51 kPa, and 37.7 ± 19.6 kPa; bulk stiffness, 6.74 ± 1.16 kPa, 8.82 ± 2.12 kPa, and 23.61 ± 8.06 kPa). Microcomputed tomography (μ-CT) assay proved that there was no statistically significant difference in the architecture of the scaffolds before or after coating. Cell viability, osteogenic differentiation, cell recruitment, and angiogenesis were determined to characterize the scaffolds and evaluate their biological responses in vitro and in vivo. The in vitro results indicate that the scaffolds developed in this study could sustain adhesion and growth of rat mesenchymal stem cells (MSCs) and promote their osteogenic differentiation. The in vivo results further demonstrated that these scaffolds could help to recruit MSCs from subcutaneous tissue, induce them to differentiate into osteoblasts, and provide the 3D environment for angiogenesis. These findings showed that the method we developed can build scaffolds with

Preservation of eccentric strength in older adults: Evidence, mechanisms and implications for training and rehabilitation.

Science.gov (United States)

Roig, Marc; Macintyre, Donna L; Eng, Janice J; Narici, Marco V; Maganaris, Constantinos N; Reid, W Darlene

2010-06-01

Overall reductions in muscle strength typically accompany the aging process. However, older adults show a relatively preserved capacity of producing eccentric strength. The preservation of eccentric strength in older adults is a well-established phenomenon, occurring indiscriminately across different muscle groups, independent of age-related architectural changes in muscle structure and velocity of movement. The mechanisms for the preservation of eccentric strength appear to be mechanical and cellular in origin and include both passive and active elements regulating muscle stiffness. The age-related accumulation of non-contractile material in the muscle-tendon unit increases passive stiffness, which might offer mechanical advantage during eccentric contractions. In addition, the preserved muscle tension and increased instantaneous stiffness of old muscle fibers during stretch increase active stiffness, which might enhance eccentric strength. The fact that the preservation of eccentric strength is present in people with chronic conditions when compared to age-matched healthy controls indicates that the aging process per se does not exclusively mediate the preservation of eccentric strength. Physical inactivity, which is common in elderly and people with chronic conditions, is a potential factor regulating the preservation of eccentric strength. When compared to concentric strength, the magnitude of preservation of eccentric strength in older adults ranges from 2% to 48% with a mean value of 21.6% from all studies. This functional reserve of eccentric strength might be clinically relevant, especially to initiate resistance training and rehabilitation programs in individuals with low levels of strength. 2010 Elsevier Inc. All rights reserved.

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

NARCIS (Netherlands)

Denning, Denise; Roos, Wouter H

2016-01-01

The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

Evidence that breast tissue stiffness is associated with risk of breast cancer.

Science.gov (United States)

Boyd, Norman F; Li, Qing; Melnichouk, Olga; Huszti, Ella; Martin, Lisa J; Gunasekara, Anoma; Mawdsley, Gord; Yaffe, Martin J; Minkin, Salomon

2014-01-01

Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers, including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer. Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of 362 women with newly diagnosed breast cancer (cases) and 656 women of the same age who did not have breast cancer (controls). Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue. Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. After adjustment for percent mammographic density by area measurements, and other risk factors, our estimate of breast tissue stiffness was significantly associated with breast cancer (odds ratio = 1.21, 95% confidence interval = 1.03, 1.43, p = 0.02) and improved breast cancer risk prediction in models with percent mammographic density, by both area and volume measurements. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement.

The link between exercise and titin passive stiffness.

Science.gov (United States)

Lalande, Sophie; Mueller, Patrick J; Chung, Charles S

2017-09-01

What is the topic of this review? This review focuses on how in vivo and molecular measurements of cardiac passive stiffness can predict exercise tolerance and how exercise training can reduce cardiac passive stiffness. What advances does it highlight? This review highlights advances in understanding the relationship between molecular (titin-based) and in vivo (left ventricular) passive stiffness, how passive stiffness modifies exercise tolerance, and how exercise training may be therapeutic for cardiac diseases with increased passive stiffness. Exercise can help alleviate the negative effects of cardiovascular disease and cardiovascular co-morbidities associated with sedentary behaviour; this may be especially true in diseases that are associated with increased left ventricular passive stiffness. In this review, we discuss the inverse relationship between exercise tolerance and cardiac passive stiffness. Passive stiffness is the physical property of cardiac muscle to produce a resistive force when stretched, which, in vivo, is measured using the left ventricular end diastolic pressure-volume relationship or is estimated using echocardiography. The giant elastic protein titin is the major contributor to passive stiffness at physiological muscle (sarcomere) lengths. Passive stiffness can be modified by altering titin isoform size or by post-translational modifications. In both human and animal models, increased left ventricular passive stiffness is associated with reduced exercise tolerance due to impaired diastolic filling, suggesting that increased passive stiffness predicts reduced exercise tolerance. At the same time, exercise training itself may induce both short- and long-term changes in titin-based passive stiffness, suggesting that exercise may be a treatment for diseases associated with increased passive stiffness. Direct modification of passive stiffness to improve exercise tolerance is a potential therapeutic approach. Titin passive stiffness itself may

Biomechanics of cellular solids.

Science.gov (United States)

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Efficient Method for Calculating the Composite Stiffness of Parabolic Leaf Springs with Variable Stiffness for Vehicle Rear Suspension

Directory of Open Access Journals (Sweden)

Wen-ku Shi

2016-01-01

Full Text Available The composite stiffness of parabolic leaf springs with variable stiffness is difficult to calculate using traditional integral equations. Numerical integration or FEA may be used but will require computer-aided software and long calculation times. An efficient method for calculating the composite stiffness of parabolic leaf springs with variable stiffness is developed and evaluated to reduce the complexity of calculation and shorten the calculation time. A simplified model for double-leaf springs with variable stiffness is built, and a composite stiffness calculation method for the model is derived using displacement superposition and material deformation continuity. The proposed method can be applied on triple-leaf and multileaf springs. The accuracy of the calculation method is verified by the rig test and FEA analysis. Finally, several parameters that should be considered during the design process of springs are discussed. The rig test and FEA analytical results indicate that the calculated results are acceptable. The proposed method can provide guidance for the design and production of parabolic leaf springs with variable stiffness. The composite stiffness of the leaf spring can be calculated quickly and accurately when the basic parameters of the leaf spring are known.

Design of a cosmetic glove stiffness compensation mechanism for toddler-sized hand prostheses

NARCIS (Netherlands)

Bos, R.A.; Plettenburg, D.H.

2017-01-01

The addition of a cosmetic glove to an upper limb prosthesis has a distinct effect on the cosmetic value, but its viscoelastic behaviour adds a substantial amount of stiffness and hysteresis to the system. As a result, the overall usability of the prosthesis is degraded. A novel negative

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

Science.gov (United States)

Kubben, Nard; Misteli, Tom

2017-10-01

Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

Comparison of cervical spine stiffness in individuals with chronic nonspecific neck pain and asymptomatic individuals.

Science.gov (United States)

Ingram, Lewis A; Snodgrass, Suzanne J; Rivett, Darren A

2015-03-01

Clinical measurement, cross-sectional. To determine if spinal joint stiffness is different in individuals with nonspecific neck pain, and whether stiffness magnitude is associated with pain intensity and disability. Manual therapists commonly evaluate spinal joint stiffness in patients presenting with nonspecific neck pain. However, a relationship between stiffness and neck pain has not yet been demonstrated. Spinal stiffness at C7 was objectively measured in participants with chronic nonspecific neck pain whose symptomatic spinal level was identified as C7 (n = 12) and in age- and sex-matched asymptomatic controls (n = 12). Stiffness (slope of the linear region of the force-displacement curve) was quantified using a device that applied 5 standardized mechanical force cycles to the C7 spinous process, while concurrently measuring displacement and resistance to movement. Stiffness was compared between groups using an independent t test. Spearman rho and Pearson r were used to determine the extent to which stiffness magnitude was associated with pain intensity (visual analog scale) and level of disability (Neck Disability Index), respectively, in the group with neck pain. Participants with nonspecific neck pain had greater spinal joint stiffness at C7 compared with asymptomatic individuals (mean difference, 1.78 N/mm; 95% confidence interval: 0.28, 3.27; P = .022). However, stiffness magnitude in the group with neck pain was not associated (P>.05) with pain intensity or level of disability. These preliminary results suggest that cervical spine stiffness may be greater in the presence of nonspecific neck pain. However, judgments regarding pain intensity and level of disability should not be inferred from examinations of spinal joint stiffness.

Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients

Directory of Open Access Journals (Sweden)

Daniel Bia

2015-01-01

Full Text Available Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP. Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels. Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV in a central arterial pathway (carotid-femoral and in a peripheral pathway (carotid-brachial. A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups. Results. Only carotid-femoral stiffness was positively associated (P<0.05 with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration. Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP.

Cellular contractility and substrate elasticity: a numerical investigation of the actin cytoskeleton and cell adhesion.

Science.gov (United States)

Ronan, William; Deshpande, Vikram S; McMeeking, Robert M; McGarry, J Patrick

2014-04-01

Numerous experimental studies have established that cells can sense the stiffness of underlying substrates and have quantified the effect of substrate stiffness on stress fibre formation, focal adhesion area, cell traction, and cell shape. In order to capture such behaviour, the current study couples a mixed mode thermodynamic and mechanical framework that predicts focal adhesion formation and growth with a material model that predicts stress fibre formation, contractility, and dissociation in a fully 3D implementation. Simulations reveal that SF contractility plays a critical role in the substrate-dependent response of cells. Compliant substrates do not provide sufficient tension for stress fibre persistence, causing dissociation of stress fibres and lower focal adhesion formation. In contrast, cells on stiffer substrates are predicted to contain large amounts of dominant stress fibres. Different levels of cellular contractility representative of different cell phenotypes are found to alter the range of substrate stiffness that cause the most significant changes in stress fibre and focal adhesion formation. Furthermore, stress fibre and focal adhesion formation evolve as a cell spreads on a substrate and leading to the formation of bands of fibres leading from the cell periphery over the nucleus. Inhibiting the formation of FAs during cell spreading is found to limit stress fibre formation. The predictions of this mutually dependent material-interface framework are strongly supported by experimental observations of cells adhered to elastic substrates and offer insight into the inter-dependent biomechanical processes regulating stress fibre and focal adhesion formation.

Stiffness Customization and Patterning for Property Modulation of Silicone-Based Soft Pneumatic Actuators.

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Sun, Yi; Yap, Hong Kai; Liang, Xinquan; Guo, Jin; Qi, Peng; Ang, Marcelo H; Yeow, Chen-Hua

2017-09-01

Soft pneumatic actuators (SPAs), as novel types of motion drivers for robotic devices, excel in many applications, such as rehabilitation and biomimicry, which demand compliance and softness. To further expand their scope of utilization, the SPAs should be customizable to meet the distinctive requirements of different applications. This article proposes a novel perspective on the SPA working mechanism based on stiffness distribution and then presents a versatile method called stiffness customization and patterning (SCP) for SPA body stiffness layout as a novel attempt to customize SPAs with distinctive properties. We fabricated a hybrid type of material combining unstretchable material and silicone with customizable aggregated elasticity. The tensile results showed that embedding unstretchable material directly increases the stiffness of the hybrid material sample, and our stress-strain model for SCP is able to adequately predict the elasticity of hybrid samples with specific material ratios. By applying this approach to bending-type SPAs, we are able to mitigate SPA buckling, a main failure mode of SPAs, and improve the SPA tip force by using hybrid material with globally increased stiffness. We also diversify bending modalities with different stiffness configurations in the hybrid material. SCP offers numerous ways to engineer SPAs for more applications.

Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

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Orsini, Caitlin A.; Maren, Stephen

2012-01-01

Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

Differential rigor development in red and white muscle revealed by simultaneous measurement of tension and stiffness.

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Kobayashi, Masahiko; Takemori, Shigeru; Yamaguchi, Maki

2004-02-10

Based on the molecular mechanism of rigor mortis, we have proposed that stiffness (elastic modulus evaluated with tension response against minute length perturbations) can be a suitable index of post-mortem rigidity in skeletal muscle. To trace the developmental process of rigor mortis, we measured stiffness and tension in both red and white rat skeletal muscle kept in liquid paraffin at 37 and 25 degrees C. White muscle (in which type IIB fibres predominate) developed stiffness and tension significantly more slowly than red muscle, except for soleus red muscle at 25 degrees C, which showed disproportionately slow rigor development. In each of the examined muscles, stiffness and tension developed more slowly at 25 degrees C than at 37 degrees C. In each specimen, tension always reached its maximum level earlier than stiffness, and then decreased more rapidly and markedly than stiffness. These phenomena may account for the sequential progress of rigor mortis in human cadavers.

Unidirectional variable stiffness hydraulic actuator for load-carrying knee exoskeleton

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Jun Zhu

2017-01-01

Full Text Available This article presents the design and experimental testing of a unidirectional variable stiffness hydraulic actuator for load-carrying knee exoskeleton. The proposed actuator is designed for mimicking the high-efficiency passive behavior of biological knee and providing actively assistance in locomotion. The adjustable passive compliance of exoskeletal knee is achieved through a variable ratio lever mechanism with linear elastic element. A compact customized electrohydraulic system is also designed to accommodate application demands. Preliminary experimental results show the prototype has good performances in terms of stiffness regulation and joint torque control. The actuator is also implemented in an exoskeleton knee joint, resulting in anticipant human-like passive compliance behavior.

Mesenchymal stem cell adhesion but not plasticity is affected by high substrate stiffness

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Janice Kal Van Tam, Koichiro Uto, Mitsuhiro Ebara, Stefania Pagliari, Giancarlo Forte and Takao Aoyagi

2012-01-01

Full Text Available The acknowledged ability of synthetic materials to induce cell-specific responses regardless of biological supplies provides tissue engineers with the opportunity to find the appropriate materials and conditions to prepare tissue-targeted scaffolds. Stem and mature cells have been shown to acquire distinct morphologies in vitro and to modify their phenotype when grown on synthetic materials with tunable mechanical properties. The stiffness of the substrate used for cell culture is likely to provide cells with mechanical cues mimicking given physiological or pathological conditions, thus affecting the biological properties of cells. The sensitivity of cells to substrate composition and mechanical properties resides in multiprotein complexes called focal adhesions, whose dynamic modification leads to cytoskeleton remodeling and changes in gene expression. In this study, the remodeling of focal adhesions in human mesenchymal stem cells in response to substrate stiffness was followed in the first phases of cell–matrix interaction, using poly-ε-caprolactone planar films with similar chemical composition and different elasticity. As compared to mature dermal fibroblasts, mesenchymal stem cells showed a specific response to substrate stiffness, in terms of adhesion, as a result of differential focal adhesion assembly, while their multipotency as a bulk was not significantly affected by matrix compliance. Given the sensitivity of stem cells to matrix mechanics, the mechanobiology of such cells requires further investigations before preparing tissue-specific scaffolds.

Coupled elasticity–diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles

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Wang, Jizeng; Li, Long

2015-01-01

Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity–diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand–receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand–receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. PMID:25411410

VCODE, Ordinary Differential Equation Solver for Stiff and Non-Stiff Problems

International Nuclear Information System (INIS)

Cohen, Scott D.; Hindmarsh, Alan C.

2001-01-01

1 - Description of program or function: CVODE is a package written in ANSI standard C for solving initial value problems for ordinary differential equations. It solves both stiff and non stiff systems. In the stiff case, it includes a variety of options for treating the Jacobian of the system, including dense and band matrix solvers, and a preconditioned Krylov (iterative) solver. 2 - Method of solution: Integration is by Adams or BDF (Backward Differentiation Formula) methods, at user option. Corrector iteration is by functional iteration or Newton iteration. For the solution of linear systems within Newton iteration, users can select a dense solver, a band solver, a diagonal approximation, or a preconditioned Generalized Minimal Residual (GMRES) solver. In the dense and band cases, the user can supply a Jacobian approximation or let CVODE generate it internally. In the GMRES case, the pre-conditioner is user-supplied

Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

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Mo, Xuejun; Li, Qiushi; Yi Lui, Lena Wai; Zheng, Baixue; Kang, Chiang Huen; Nugraha, Bramasta; Yue, Zhilian; Jia, Rui Rui; Fu, Hong Xia; Choudhury, Deepak; Arooz, Talha; Yan, Jie; Lim, Chwee Teck; Shen, Shali; Hong Tan, Choon; Yu, Hanry

2010-10-01

Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications. 2010 Elsevier Ltd. All rights reserved.

Hemodynamic and arterial stiffness differences between African-Americans and Caucasians after maximal exercise.

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Yan, Huimin; Ranadive, Sushant M; Heffernan, Kevin S; Lane, Abbi D; Kappus, Rebecca M; Cook, Marc D; Wu, Pei-Tzu; Sun, Peng; Harvey, Idethia S; Woods, Jeffrey A; Wilund, Kenneth R; Fernhall, Bo

2014-01-01

African-American (AA) men have higher arterial stiffness and augmentation index (AIx) than Caucasian-American (CA) men. Women have greater age-associated increases in arterial stiffness and AIx than men. This study examined racial and sex differences in arterial stiffness and central hemodynamics at rest and after an acute bout of maximal exercise in young healthy individuals. One hundred young, healthy individuals (28 AA men, 24 AA women, 25 CA men, and 23 CA women) underwent measurements of aortic blood pressure (BP) and arterial stiffness at rest and 15 and 30 min after an acute bout of graded maximal aerobic exercise. Aortic BP and AIx were derived from radial artery applanation tonometry. Aortic stiffness (carotid-femoral) was measured via pulse wave velocity. Aortic stiffness was increased in AA subjects but not in CA subjects (P < 0.05) after an acute bout of maximal cycling exercise, after controlling for body mass index. Aortic BP decreased after exercise in CA subjects but not in AA subjects (P < 0.05). Women exhibited greater reductions in AIx after maximal aerobic exercise compared with men (P < 0.05). In conclusion, race and sex impact vascular and central hemodynamic responses to exercise. Young AA and CA subjects exhibited differential responses in central stiffness and central BP after acute maximal exercise. Premenopausal women had greater augmented pressure at rest and after maximal aerobic exercise than men. Future research is needed to examine the potential mechanisms.

Molecular and cellular mechanisms of aortic stenosis.

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Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Experimental challenges to stiffness as a transport paradigm

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Luce, T. C.; Burrell, K. H.; Holland, C.; Marinoni, A.; Petty, C. C.; Smith, S. P.; Austin, M. E.; Grierson, B. A.; Zeng, L.

2018-02-01

Two power scans were carried out in H-mode plasmas in DIII-D; one employed standard co-current neutral beam injection (NBI), while the other used a mixture of co-current and counter-current NBI to scan power while holding the torque to a low fixed value. Analysis of the ion and electron heat transport, ion toroidal angular momentum transport, and thermal deuterium transport from these scans is presented. Invariance of the gradients or gradient scalelengths, as might be expected from stiff transport, was not generally observed. When invariance was seen, it was not accompanied by a strong increase in transport, except in the case of the absolute deuterium ion transport. Conduction in the ion channel is the dominant energy loss mechanism. The variation of the ion heat transport with applied power is similar for the co-injection and fixed torque scans, indicating that E  ×  B shearing is not determining the plasma response to additional power. There is however, a quantitative difference in the transport between the two scans, indicating E  ×  B shearing does play a role in the transport. Comparison of these results with a previous experiment that directly probed stiffness at a single radius leads to the following conclusion: while local stiffness as formally defined may hold, invariance of the gradients or normalized scalelengths does not follow from stiff transport in more practical scaling experiments, such as the power scans discussed here. Possible reasons for the lack of correspondence between the local picture and the global expectations are discussed.

Effects of plyometric training on passive stiffness of gastrocnemii muscles and Achilles tendon.

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Fouré, Alexandre; Nordez, Antoine; Cornu, Christophe

2012-08-01

Plyometric training is commonly used to improve athletic performance; however, it is unclear how each component of the muscle-tendon complex (MTC) is affected by this intervention. The effects of 14 weeks of plyometric training on the passive stiffness of the gastrocnemii muscles and Achilles tendon was determined simultaneously to assess possible local adaptations of elastic properties. The passive force-length relationship of the gastrocnemii MTC and elongation of the gastrocnemii muscles were determined using ultrasonography during passive cyclic stretching in 19 subjects divided into trained (n = 9) and control (n = 10) groups. An upward trend in stiffness of the gastrocnemii MTC (P = 0.09) and a significant increase in the intrinsic gastrocnemii muscle stiffness were found (P  0.05). Considering the lack of change in gastrocnemii muscle geometry, the change in the gastrocnemii muscle stiffness may be mainly due to a change in the intrinsic mechanical properties of the muscular tissues.

Active Magnetic Bearings Stiffness and Damping Identification from Frequency Characteristics of Control System

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Chaowu Jin

2016-01-01

Full Text Available At present, the stiffness and damping identification for active magnetic bearings (AMBs are still in the stage of theoretical analysis. The theoretical analysis indicates that if the mechanical structure and system parameters are determined, AMBs stiffness and damping are only related to frequency characteristic of control system, ignoring operating condition. More importantly, few verification methods are proposed. Considering the shortcomings of the theoretical identification, this paper obtains these coefficients from the experiment by using the magnetic bearing as a sine exciter. The identification results show that AMBs stiffness and damping have a great relationship with the control system and rotating speed. Specifically, at low rotating speed, the stiffness and damping can be obtained from the rotor static suspension by adding the same excitation frequency. However, at high speed, different from the static suspension situation, the AMBs supporting coefficients are not only related to the frequency characteristics of control system, but also related to the system operating conditions.

Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

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Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

2017-10-01

Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

Real-Time Vision-Based Stiffness Mapping †.

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Faragasso, Angela; Bimbo, João; Stilli, Agostino; Wurdemann, Helge Arne; Althoefer, Kaspar; Asama, Hajime

2018-04-26

This paper presents new findings concerning a hand-held stiffness probe for the medical diagnosis of abnormalities during palpation of soft-tissue. Palpation is recognized by the medical community as an essential and low-cost method to detect and diagnose disease in soft-tissue. However, differences are often subtle and clinicians need to train for many years before they can conduct a reliable diagnosis. The probe presented here fills this gap providing a means to easily obtain stiffness values of soft tissue during a palpation procedure. Our stiffness sensor is equipped with a multi degree of freedom (DoF) Aurora magnetic tracker, allowing us to track and record the 3D position of the probe whilst examining a tissue area, and generate a 3D stiffness map in real-time. The stiffness probe was integrated in a robotic arm and tested in an artificial environment representing a good model of soft tissue organs; the results show that the sensor can accurately measure and map the stiffness of a silicon phantom embedded with areas of varying stiffness.

Real-Time Vision-Based Stiffness Mapping †

Directory of Open Access Journals (Sweden)

Angela Faragasso

2018-04-01

Full Text Available This paper presents new findings concerning a hand-held stiffness probe for the medical diagnosis of abnormalities during palpation of soft-tissue. Palpation is recognized by the medical community as an essential and low-cost method to detect and diagnose disease in soft-tissue. However, differences are often subtle and clinicians need to train for many years before they can conduct a reliable diagnosis. The probe presented here fills this gap providing a means to easily obtain stiffness values of soft tissue during a palpation procedure. Our stiffness sensor is equipped with a multi degree of freedom (DoF Aurora magnetic tracker, allowing us to track and record the 3D position of the probe whilst examining a tissue area, and generate a 3D stiffness map in real-time. The stiffness probe was integrated in a robotic arm and tested in an artificial environment representing a good model of soft tissue organs; the results show that the sensor can accurately measure and map the stiffness of a silicon phantom embedded with areas of varying stiffness.

Dynamic stiffness of suction caissons - vertical vibrations

Energy Technology Data Exchange (ETDEWEB)

Ibsen, Lars Bo; Liingaard, M.; Andersen, Lars

2006-12-15

The dynamic response of offshore wind turbines are affected by the properties of the foundation and the subsoil. The purpose of this report is to evaluate the dynamic soil-structure interaction of suction caissons for offshore wind turbines. The investigation is limited to a determination of the vertical dynamic stiffness of suction caissons. The soil surrounding the foundation is homogenous with linear viscoelastic properties. The dynamic stiffness of the suction caisson is expressed by dimensionless frequency-dependent dynamic stiffness coefficients corresponding to the vertical degree of freedom. The dynamic stiffness coefficients for the foundations are evaluated by means of a dynamic three-dimensional coupled Boundary Element/Finite Element model. Comparisons are made with known analytical and numerical solutions in order to evaluate the static and dynamic behaviour of the Boundary Element/Finite Element model. The vertical frequency dependent stiffness has been determined for different combinations of the skirt length, Poisson's ratio and the ratio between soil stiffness and skirt stiffness. Finally the dynamic behaviour at high frequencies is investigated. (au)

Micromechanical contact stiffness devices and application for calibrating contact resonance atomic force microscopy

Science.gov (United States)

Rosenberger, Matthew R.; Chen, Sihan; Prater, Craig B.; King, William P.

2017-01-01

This paper reports the design, fabrication, and characterization of micromechanical devices that can present an engineered contact stiffness to an atomic force microscope (AFM) cantilever tip. These devices allow the contact stiffness between the AFM tip and a substrate to be easily and accurately measured, and can be used to calibrate the cantilever for subsequent mechanical property measurements. The contact stiffness devices are rigid copper disks of diameters 2-18 μm integrated onto a soft silicone substrate. Analytical modeling and finite element simulations predict the elastic response of the devices. Measurements of tip-sample interactions during quasi-static force measurements compare well with modeling simulation, confirming the expected elastic response of the devices, which are shown to have contact stiffness 32-156 N m-1. To demonstrate one application, we use the disk sample to calibrate three resonant modes of a U-shaped AFM cantilever actuated via Lorentz force, at approximately 220, 450, and 1200 kHz. We then use the calibrated cantilever to determine the contact stiffness and elastic modulus of three polymer samples at these modes. The overall approach allows cantilever calibration without prior knowledge of the cantilever geometry or its resonance modes, and could be broadly applied to both static and dynamic measurements that require AFM calibration against a known contact stiffness.

Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli.

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Rene Olivares-Navarrete

Full Text Available Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1 in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.

Functions of fish skin: flexural stiffness and steady swimming of longnose gar, Lepisosteus osseus

Science.gov (United States)

Long; Hale; Mchenry; Westneat

1996-01-01

The functions of fish skin during swimming remain enigmatic. Does skin stiffen the body and alter the propagation of the axial undulatory wave? To address this question, we measured the skin's in situ flexural stiffness and in vivo mechanical role in the longnose gar Lepisosteus osseus. To measure flexural stiffness, dead gar were gripped and bent in a device that measured applied bending moment (N m) and the resulting midline curvature (m-1). From these values, the flexural stiffness of the body (EI in N m2) was calculated before and after sequential alterations of skin structure. Cutting of the dermis between two caudal scale rows significantly reduced the flexural stiffness of the body and increased the neutral zone of curvature, a region of bending without detectable stiffness. Neither bending property was significantly altered by the removal of a caudal scale row. These alterations in skin structure were also made in live gar and the kinematics of steady swimming was measured before and after each treatment. Cutting of the dermis between two caudal scale rows, performed under anesthesia, changed the swimming kinematics of the fish: tailbeat frequency (Hz) and propulsive wave speed (body lengths per second, L s-1) decreased, while the depth (in L) of the trailing edge of the tail increased. The decreases in tailbeat frequency and wave speed are consistent with predictions of the theory of forced, harmonic vibrations; wave speed, if equated with resonance frequency, is proportional to the square root of a structure's stiffness. While it did not significantly reduce the body's flexural stiffness, surgical removal of a caudal scale row resulted in increased tailbeat amplitude and the relative total hydrodynamic power. In an attempt to understand the specific function of the scale row, we propose a model in which a scale row resists medio-lateral force applied by a single myomere, thus functioning to enhance mechanical advantage for bending. Finally, surgical

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

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Ryota Domura

2017-06-01

Full Text Available The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments and different stiffness of the polymeric substrates (poly(l-lactic acid and poly(ε-caprolactone, PLLA and PCL, respectively as well as collagen substrates (coat and gel to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7. The morphological spreading parameter (nucleus/cytoplasm area ratio induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50 of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells.

Science.gov (United States)

Domura, Ryota; Sasaki, Rie; Ishikawa, Yuma; Okamoto, Masami

2017-06-06

The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC 50 ) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Non-invasive assessment of muscle stiffness in patients with Duchenne muscular dystrophy.

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Lacourpaille, Lilian; Hug, François; Guével, Arnaud; Péréon, Yann; Magot, Armelle; Hogrel, Jean-Yves; Nordez, Antoine

2015-02-01

Assessment of muscle mechanical properties may provide clinically valuable information for follow-up of patients with Duchenne muscular dystrophy (DMD) through the course of their disease. In this study we aimed to assess the effect of DMD on stiffness of relaxed muscles using elastography (supersonic shear imaging). Fourteen DMD patients and 13 control subjects were studied. Six muscles were measured at 2 muscle lengths (shortened and stretched): gastrocnemius medialis (GM); tibialis anterior (TA); vastus lateralis (VL); biceps brachii (BB); triceps brachii (TB); and abductor digiti minimi (ADM). Stiffness was significantly higher in DMD patients compared with controls for all the muscles (main effect for population, P muscle lengths) to large (d = 0.86 for BB/stretched). Supersonic shear imaging is a sensitive non-invasive technique to assess the increase in muscle stiffness associated with DMD. © 2014 Wiley Periodicals, Inc.

Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype.

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Floren, Michael; Bonani, Walter; Dharmarajan, Anirudh; Motta, Antonella; Migliaresi, Claudio; Tan, Wei

2016-02-01

Cell-matrix and cell-biomolecule interactions play critical roles in a diversity of biological events including cell adhesion, growth, differentiation, and apoptosis. Evidence suggests that a concise crosstalk of these environmental factors may be required to direct stem cell differentiation toward matured cell type and function. However, the culmination of these complex interactions to direct stem cells into highly specific phenotypes in vitro is still widely unknown, particularly in the context of implantable biomaterials. In this study, we utilized tunable hydrogels based on a simple high pressure CO2 method and silk fibroin (SF) the structural protein of Bombyx mori silk fibers. Modification of SF protein starting water solution concentration results in hydrogels of variable stiffness while retaining key structural parameters such as matrix pore size and β-sheet crystallinity. To further resolve the complex crosstalk of chemical signals with matrix properties, we chose to investigate the role of 3D hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Our data revealed the potential to upregulate matured vascular smooth muscle cell phenotype (myosin heavy chain expression) of hMSCs by employing appropriate matrix stiffness and growth factor (within 72h). Overall, our observations suggest that chemical and physical stimuli within the cellular microenvironment are tightly coupled systems involved in the fate decisions of hMSCs. The production of tunable scaffold materials that are biocompatible and further specialized to mimic tissue-specific niche environments will be of considerable value to future tissue engineering platforms. This article investigates the role of silk fibroin hydrogel stiffness and transforming growth factor (TGF-β1), with the aim of correlating the effects on the vascular commitment of human mesenchymal stem cells. Specifically, we

Observer-Based Human Knee Stiffness Estimation.

Science.gov (United States)

Misgeld, Berno J E; Luken, Markus; Riener, Robert; Leonhardt, Steffen

2017-05-01

We consider the problem of stiffness estimation for the human knee joint during motion in the sagittal plane. The new stiffness estimator uses a nonlinear reduced-order biomechanical model and a body sensor network (BSN). The developed model is based on a two-dimensional knee kinematics approach to calculate the angle-dependent lever arms and the torques of the muscle-tendon-complex. To minimize errors in the knee stiffness estimation procedure that result from model uncertainties, a nonlinear observer is developed. The observer uses the electromyogram (EMG) of involved muscles as input signals and the segmental orientation as the output signal to correct the observer-internal states. Because of dominating model nonlinearities and nonsmoothness of the corresponding nonlinear functions, an unscented Kalman filter is designed to compute and update the observer feedback (Kalman) gain matrix. The observer-based stiffness estimation algorithm is subsequently evaluated in simulations and in a test bench, specifically designed to provide robotic movement support for the human knee joint. In silico and experimental validation underline the good performance of the knee stiffness estimation even in the cases of a knee stiffening due to antagonistic coactivation. We have shown the principle function of an observer-based approach to knee stiffness estimation that employs EMG signals and segmental orientation provided by our own IPANEMA BSN. The presented approach makes realtime, model-based estimation of knee stiffness with minimal instrumentation possible.

Load bearing and stiffness tailored NiTi implants produced by additive manufacturing: a simulation study

Science.gov (United States)

Rahmanian, Rasool; Shayesteh Moghaddam, Narges; Haberland, Christoph; Dean, David; Miller, Michael; Elahinia, Mohammad

2014-03-01

Common metals for stable long-term implants (e.g. stainless steel, Titanium and Titanium alloys) are much stiffer than spongy cancellous and even stiffer than cortical bone. When bone and implant are loaded this stiffness mismatch results in stress shielding and as a consequence, degradation of surrounding bony structure can lead to disassociation of the implant. Due to its lower stiffness and high reversible deformability, which is associated with the superelastic behavior, NiTi is an attractive biomaterial for load bearing implants. However, the stiffness of austenitic Nitinol is closer to that of bone but still too high. Additive manufacturing provides, in addition to the fabrication of patient specific implants, the ability to solve the stiffness mismatch by adding engineered porosity to the implant. This in turn allows for the design of different stiffness profiles in one implant tailored to the physiological load conditions. This work covers a fundamental approach to bring this vision to reality. At first modeling of the mechanical behavior of different scaffold designs are presented as a proof of concept of stiffness tailoring. Based on these results different Nitinol scaffolds can be produced by additive manufacturing.

Measurement of passive ankle stiffness in subjects with chronic hemiparesis using a novel ankle robot

Science.gov (United States)

Roy, Anindo; Bever, Christopher T.; Forrester, Larry W.; Macko, Richard F.; Hogan, Neville

2011-01-01

Our objective in this study was to assess passive mechanical stiffness in the ankle of chronic hemiparetic stroke survivors and to compare it with those of healthy young and older (age-matched) individuals. Given the importance of the ankle during locomotion, an accurate estimate of passive ankle stiffness would be valuable for locomotor rehabilitation, potentially providing a measure of recovery and a quantitative basis to design treatment protocols. Using a novel ankle robot, we characterized passive ankle stiffness both in sagittal and in frontal planes by applying perturbations to the ankle joint over the entire range of motion with subjects in a relaxed state. We found that passive stiffness of the affected ankle joint was significantly higher in chronic stroke survivors than in healthy adults of a similar cohort, both in the sagittal as well as frontal plane of movement, in three out of four directions tested with indistinguishable stiffness values in plantarflexion direction. Our findings are comparable to the literature, thus indicating its plausibility, and, to our knowledge, report for the first time passive stiffness in the frontal plane for persons with chronic stroke and older healthy adults. PMID:21346215

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

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Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Intratrabecular distribution of tissue stiffness and mineralization in developing trabecular bone

NARCIS (Netherlands)

Mulder, L.; Koolstra, J.H.; Toonder, den J.M.J.; Eijden, van T.M.G.J.

2007-01-01

The purpose of this study was to investigate the relation between bone tissue stiffness and degree of mineralization distribution and to examine possible changes during prenatal development. Understanding this may provide insight into adaptation processes and into deformation mechanisms of the bone

Stiffness analysis for the micromagnetic standard problem No. 4

International Nuclear Information System (INIS)

Tsiantos, Vassilios D.; Suess, Dieter; Schrefl, Thomas; Fidler, Josef

2001-01-01

In this article solutions to micromagnetic standard problem No. 4, a 500-nmx125-nm-wide NiFe film, are presented. A three-dimensional-finite element simulation based on the solution of the Gilbert equation has been used. The simulations show that two different reversal mechanisms occur for the two different applied fields. For a field at 170 degree counterclockwise from the saturation direction there is a nonuniform rotation of magnetization towards the direction of the applied field, with the magnetization at the ends rotating faster than the magnetization in the center. For a field at 190 degree counterclockwise from the saturation direction the magnetization at the ends and in the center rotate in opposite directions leading to the formation of a 360 degree wall after 0.22 ns associated with a peak in the exchange energy. Moreover, the time for the magnetization component parallel to the long axis to cross the zero is 0.136 and 0.135 ns for field 1 and field 2, respectively. The stiffness of the problem has been investigated solving the system of ordinary differential equations with a nonstiff method (Adams) and a stiff one (backward differentiation formula, BDF). For the measure of stiffness the ratio of the total number of time steps (nst) taken by the two solvers, that is nst(Adams)/nst(BDF), has been used. This ratio is 0.784 for field 1 and 0.593 for field 2, which means that the nonstiff method (Adams) uses larger time steps than the stiff method (BDF) and consequently the systems are not stiff. The average time step for the Adams method was 0.2 ps for both fields. [copyright] 2001 American Institute of Physics

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases.

Science.gov (United States)

Ding, Suet Lee Shirley; Kumar, Suresh; Mok, Pooi Ling

2017-07-28

The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

Mitochondrial and cellular mechanisms for managing lipid excess

Directory of Open Access Journals (Sweden)

Miguel A Aon

2014-07-01

Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

Influence of Passive Joint Stiffness on Proprioceptive Acuity in Individuals With Functional Instability of the Ankle.

Science.gov (United States)

Marinho, Hellen Veloso Rocha; Amaral, Giovanna Mendes; de Souza Moreira, Bruno; Araújo, Vanessa Lara; Souza, Thales Rezende; Ocarino, Juliana Melo; da Fonseca, Sérgio Teixeira

2017-12-01

Study Design Controlled laboratory study, cross-sectional. Background Deficits in ankle proprioceptive acuity have been reported in persons with functional instability of the ankle. Passive stiffness has been proposed as a possible mechanism underlying proprioceptive acuity. Objective To compare proprioceptive acuity and passive ankle stiffness in persons with and without functional ankle instability, and to assess the influence of passive joint stiffness on proprioceptive acuity in persons with functional ankle instability. Methods A sample of 18 subjects with and 18 without complaints of functional ankle instability following lateral ankle sprain participated. An isokinetic dynamometer was used to compare motion perception threshold, passive position sense, and passive ankle stiffness between groups. To evaluate the influence of passive stiffness on proprioceptive acuity, individuals in the lateral functional ankle instability group were divided into 2 subgroups: "high" and "low" passive ankle stiffness. Results The functional ankle instability group exhibited increased motion perception threshold when compared with the corresponding limb of the control group. Between-group differences were not found for passive position sense and passive ankle stiffness. Those in the functional ankle instability group with higher passive ankle stiffness had smaller motion perception thresholds than those with lower passive ankle stiffness. Conclusion Unlike motion perception threshold, passive position sense is not affected by the presence of functional ankle instability. Passive ankle stiffness appears to influence proprioceptive acuity in persons with functional ankle instability. J Orthop Sports Phys Ther 2017;47(12):899-905. Epub 7 Oct 2017. doi:10.2519/jospt.2017.7030.

Topological interlocking provides stiffness to stochastically micro-cracked materials beyond the transport percolation limit

Science.gov (United States)

Pal, Anirban; Picu, Catalin; Lupulescu, Marian V.

We study the mechanical behavior of two-dimensional, stochastically microcracked continua in the range of crack densities close to, and above the transport percolation threshold. We show that these materials retain stiffness up to crack densities much larger than the transport percolation threshold, due to topological interlocking of sample sub-domains. Even with a linear constitutive law for the continuum, the mechanical behavior becomes non-linear in the range of crack densities bounded by the transport and stiffness percolation thresholds. The effect is due to the fractal nature of the fragmentation process and is not linked to the roughness of individual cracks. We associate this behavior to that of itacolumite, a sandstone that exhibits unusual flexibility.

The role of tissue renin angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness

Directory of Open Access Journals (Sweden)

Annayya R Aroor

2013-10-01

Full Text Available Epidemiological studies support the notion that arterial stiffness is an independent predictor of adverse cardiovascular events contributing significantly to systolic hypertension, impaired ventricular-arterial coupling and diastolic dysfunction, impairment in myocardial oxygen supply and demand, and progression of kidney disease. Although arterial stiffness is associated with aging, it is accelerated in the presence of obesity and diabetes. The prevalence of arterial stiffness parallels the increase of obesity that is occurring in epidemic proportions and is partly driven by a sedentary life style and consumption of a high fructose, high salt and high fat western diet. Although the underlying mechanisms and mediators of arterial stiffness are not well understood, accumulating evidence supports the role of insulin resistance and endothelial dysfunction. The local tissue renin angiotensin aldosterone system (RAAS in the vascular tissue and immune cells and perivascular adipose tissue is recognized as an important element involved in endothelial dysfunction which contributes significantly to arterial stiffness. Activation of vascular RAAS is seen in humans and animal models of obesity and diabetes, and associated with enhanced oxidative stress and inflammation in the vascular tissue. The cross talk between angiotensin and aldosterone underscores the importance of mineralocorticoid receptors in modulation of insulin resistance, decreased bioavailability of nitric oxide, endothelial dysfunction and arterial stiffness. In addition, both innate and adaptive immunity are involved in this local tissue activation of RAAS. In this review we will attempt to present a unifying mechanism of how environmental and immunological factors are involved in this local tissue RAAS activation, and the role of this process in the development of endothelial dysfunction and arterial stiffness and targeting tissue RAAS activation.

Architected Lattices with High Stiffness and Toughness via Multicore-Shell 3D Printing.

Science.gov (United States)

Mueller, Jochen; Raney, Jordan R; Shea, Kristina; Lewis, Jennifer A

2018-03-01

The ability to create architected materials that possess both high stiffness and toughness remains an elusive goal, since these properties are often mutually exclusive. Natural materials, such as bone, overcome such limitations by combining different toughening mechanisms across multiple length scales. Here, a new method for creating architected lattices composed of core-shell struts that are both stiff and tough is reported. Specifically, these lattices contain orthotropic struts with flexible epoxy core-brittle epoxy shell motifs in the absence and presence of an elastomeric silicone interfacial layer, which are fabricated by a multicore-shell, 3D printing technique. It is found that architected lattices produced with a flexible core-elastomeric interface-brittle shell motif exhibit both high stiffness and toughness. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rotational stiffness of American football shoes affects ankle biomechanics and injury severity.

Science.gov (United States)

Button, Keith D; Braman, Jerrod E; Davison, Mark A; Wei, Feng; Schaeffer, Maureen C; Haut, Roger C

2015-06-01

While previous studies have investigated the effect of shoe-surface interaction on injury risk, few studies have examined the effect of rotational stiffness of the shoe. The hypothesis of the current study was that ankles externally rotated to failure in shoes with low rotational stiffness would allow more talus eversion than those in shoes with a higher rotational stiffness, resulting in less severe injury. Twelve (six pairs) cadaver lower extremities were externally rotated to gross failure while positioned in 20 deg of pre-eversion and 20 deg of predorsiflexion by fixing the distal end of the foot, axially loading the proximal tibia, and internally rotating the tibia. One ankle in each pair was constrained by an American football shoe with a stiff upper, while the other was constrained by an American football shoe with a flexible upper. Experimental bone motions were input into specimen-specific computational models to examine levels of ligament elongation to help understand mechanisms of ankle joint failure. Ankles in flexible shoes allowed 6.7±2.4 deg of talus eversion during rotation, significantly greater than the 1.7±1.0 deg for ankles in stiff shoes (p = 0.01). The significantly greater eversion in flexible shoes was potentially due to a more natural response of the ankle during rotation, possibly affecting the injuries that were produced. All ankles failed by either medial ankle injury or syndesmotic injury, or a combination of both. Complex (more than one ligament or bone) injuries were noted in 4 of 6 ankles in stiff shoes and 1 of 6 ankles in flexible shoes. Ligament elongations from the computational model validated the experimental injury data. The current study suggested flexibility (or rotational stiffness) of the shoe may play an important role in both the severity of ankle injuries for athletes.

Design and Experimental Development of a Pneumatic Stiffness Adjustable Foot System for Biped Robots Adaptable to Bumps on the Ground

Directory of Open Access Journals (Sweden)

Xizhe Zang

2017-09-01

Full Text Available Walking on rough terrains still remains a challenge that needs to be addressed for biped robots because the unevenness on the ground can easily disrupt the walking stability. This paper proposes a novel foot system with passively adjustable stiffness for biped robots which is adaptable to small-sized bumps on the ground. The robotic foot is developed by attaching eight pneumatic variable stiffness units to the sole separately and symmetrically. Each variable stiffness unit mainly consists of a pneumatic bladder and a mechanical reversing valve. When walking on rough ground, the pneumatic bladders in contact with bumps are compressed, and the corresponding reversing valves are triggered to expel out the air, enabling the pneumatic bladders to adapt to the bumps with low stiffness; while the other pneumatic bladders remain rigid and maintain stable contact with the ground, providing support to the biped robot. The performances of the proposed foot system, including the variable stiffness mechanism, the adaptability on the bumps of different heights, and the application on a biped robot prototype are demonstrated by various experiments.

Characterizing cellular mechanical phenotypes with mechano-node-pore sensing

Science.gov (United States)

Kim, Junghyun; Han, Sewoon; Lei, Andy; Miyano, Masaru; Bloom, Jessica; Srivastava, Vasudha; Stampfer, Martha M.; Gartner, Zev J.; LaBarge, Mark A.; Sohn, Lydia L.

2018-01-01

The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these properties may be useful label-free biomarkers of various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter, resistance to compressive deformation, transverse deformation under constant strain, and recovery time after deformation. We define a new parameter, the whole-cell deformability index (wCDI), which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types. The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant, MCF-10A and BEAS-2B cell lines, and distinguishes between cells treated or untreated with cytoskeleton-perturbing small molecules. We categorize cell recovery time, ΔTr, as instantaneous (ΔTr ~ 0 ms), transient (ΔTr ≤ 40ms), or prolonged (ΔTr > 40ms), and show that the composition of recovery types, which is a consequence of changes in cytoskeletal organization, correlates with cellular transformation. Through the wCDI and cell-recovery time, mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry, but without antibody labeling. Mechano-NPS identifies mechanical phenotypes that distinguishes lineage, chronological age, and stage of malignant progression in human epithelial cells. PMID:29780657

A eutectic-alloy-infused soft actuator with sensing, tunable degrees of freedom, and stiffness properties

Science.gov (United States)

Hao, Yufei; Wang, Tianmiao; Xie, Zhexin; Sun, Wenguang; Liu, Zemin; Fang, Xi; Yang, Minxuan; Wen, Li

2018-02-01

This paper presents a soft actuator embedded with two types of eutectic alloys which enable sensing, tunable mechanical degrees of freedom (DOF), and variable stiffness properties. To modulate the stiffness of the actuator, we embedded a low melting point alloy (LMPA) in the bottom portion of the soft actuator. Different sections of the LMPA could be selectively melted by the Ni-Cr wires twined underneath. To acquire the curvature information, EGaIn (eutectic gallium indium) was infused into a microchannel surrounding the chambers of the soft actuator. Systematic experiments were performed to characterize the stiffness, tunable DOF, and sensing the bending curvature. We found that the average bending force and elasticity modulus could be increased about 35 and 4000 times, respectively, with the LMPA in a solid state. The entire LMPA could be melted from a solid to a liquid state within 12 s. In particular, up to six different motion patterns could be achieved under each pneumatic pressure of the soft actuator. Furthermore, the kinematics of the actuator under different motion patterns could be obtained by a mathematical model whose input was provided by the EGaIn sensor. For demonstration purposes, a two-fingered gripper was fabricated to grasp various objects by adjusting the DOF and mechanical stiffness.

Indentation stiffness does not discriminate between normal and degraded articular cartilage.

Science.gov (United States)

Brown, Cameron P; Crawford, Ross W; Oloyede, Adekunle

2007-08-01

Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress-strain behaviour of normal samples. We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment.

Constitutive Modelling of Resins in the Stiffness Domain

Science.gov (United States)

Klasztorny, M.

2004-09-01

An analytic method for inverting the constitutive compliance equations of viscoelasticity for resins is developed. These equations describe the HWKK/H rheological model, which makes it possible to simulate, with a good accuracy, short-, medium- and long-term viscoelastic processes in epoxy and polyester resins. These processes are of first-rank reversible isothermal type. The time histories of deviatoric stresses are simulated with three independent strain history functions of fractional and normal exponential types. The stiffness equations are described by two elastic and six viscoelastic constants having a clear physic meaning (three long-term relaxation coefficients and three relaxation times). The time histories of axiatoric stresses are simulated as perfectly elastic. The inversion method utilizes approximate constitutive stiffness equations of viscoelasticity for the HWKK/H model. The constitutive compliance equations for the model are a basis for determining the exact complex shear stiffness, whereas the approximate constitutive stiffness equations are used for determining the approximate complex shear stiffness. The viscoelastic constants in the stiffness domain are derived by equating the exact and approximate complex shear stiffnesses. The viscoelastic constants are obtained for Epidian 53 epoxy and Polimal 109 polyester resins. The accuracy of the approximate constitutive stiffness equations are assessed by comparing the approximate and exact complex shear stiffnesses. The constitutive stiffness equations for the HWKK/H model are presented in uncoupled (shear/bulk) and coupled forms. Formulae for converting the constants of shear viscoelasticity into the constants of coupled viscoelasticity are given as well.

Endoscopic add-on stiffness probe for real-time soft surface characterisation in MIS.

Science.gov (United States)

Faragasso, A; Stilli, A; Bimbo, J; Noh, Y; Liu, H; Nanayakkara, T; Dasgupta, P; Wurdemann, H A; Althoefer, K

2014-01-01

This paper explores a novel stiffness sensor which is mounted on the tip of a laparoscopic camera. The proposed device is able to compute stiffness when interacting with soft surfaces. The sensor can be used in Minimally Invasive Surgery, for instance, to localise tumor tissue which commonly has a higher stiffness when compared to healthy tissue. The purely mechanical sensor structure utilizes the functionality of an endoscopic camera to the maximum by visually analyzing the behavior of trackers within the field of view. Two pairs of spheres (used as easily identifiable features in the camera images) are connected to two springs with known but different spring constants. Four individual indenters attached to the spheres are used to palpate the surface. During palpation, the spheres move linearly towards the objective lens (i.e. the distance between lens and spheres is changing) resulting in variations of their diameters in the camera images. Relating the measured diameters to the different spring constants, a developed mathematical model is able to determine the surface stiffness in real-time. Tests were performed using a surgical endoscope to palpate silicon phantoms presenting different stiffness. Results show that the accuracy of the sensing system developed increases with the softness of the examined tissue.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

Energy Technology Data Exchange (ETDEWEB)

Liu, Lingling, E-mail: liulingling2012@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Luo, Qing, E-mail: qing.luo@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Sun, Jinghui, E-mail: sunjhemail@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Wang, Aoli, E-mail: leaf13332@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Shi, Yisong, E-mail: shiyis@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Ju, Yang, E-mail: ju@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Morita, Yasuyuki, E-mail: morita@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

2017-06-15

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

International Nuclear Information System (INIS)

Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

2017-01-01

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

On stress/strain shielding and the material stiffness paradigm for dental implants.

Science.gov (United States)

Korabi, Raoof; Shemtov-Yona, Keren; Rittel, Daniel

2017-10-01

Stress shielding considerations suggest that the dental implant material's compliance should be matched to that of the host bone. However, this belief has not been confirmed from a general perspective, either clinically or numerically. To characterize the influence of the implant stiffness on its functionality using the failure envelope concept that examines all possible combinations of mechanical load and application angle for selected stress, strain and displacement-based bone failure criteria. Those criteria represent bone yielding, remodeling, and implant primary stability, respectively MATERIALS AND METHODS: We performed numerical simulations to generate failure envelopes for all possible loading configurations of dental implants, with stiffness ranging from very low (polymer) to extremely high, through that of bone, titanium, and ceramics. Irrespective of the failure criterion, stiffer implants allow for improved implant functionality. The latter reduces with increasing compliance, while the trabecular bone experiences higher strains, albeit of an overall small level. Micromotions remain quite small irrespective of the implant's stiffness. The current paradigm favoring reduced implant material's stiffness out of concern for stress or strain shielding, or even excessive micromotions, is not supported by the present calculations, that point exactly to the opposite. © 2017 Wiley Periodicals, Inc.

The stiffness change and the increase in the ultimate capacity for a stiff pile resulting from a cyclic loading

DEFF Research Database (Denmark)

Lada, Aleksandra; Ibsen, Lars Bo; Nicolai, Giulio

In the paper the experimental results of small-scale tests on a stiff monopile are presented to outline the change in stiffness during the cyclic loading and the change in the ultimate pile capacity. The results confirm the increase of stiffness and the increase in bearing capacity resulting from...

Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

Directory of Open Access Journals (Sweden)

Irina V. Kholodenko

2017-01-01

Full Text Available The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.

Differential Polymer Structure Tunes Mechanism of Cellular Uptake and Transfection Routes of Poly(β-amino ester) Polyplexes in Human Breast Cancer Cells

OpenAIRE

Kim, Jayoung; Sunshine, Joel C.; Green, Jordan J.

2013-01-01

Successful gene delivery with non-viral particles has several barriers, including cellular uptake, endosomal escape, and nuclear transport. Understanding the mechanisms behind these steps is critical to enhancing the effectiveness of gene delivery. Polyplexes formed with poly(β-amino ester)s (PBAEs) have been shown to effectively transfer DNA to various cell types, but the mechanism of their cellular uptake has not been identified. This is the first study to evaluate the uptake mechanism of P...

Variable Stiffness Actuators: Modeling, Control, and Application to Compliant Bipedal Walking

NARCIS (Netherlands)

Visser, L.C.

2013-01-01

Robots are traditionally used in factory environments, where they perform tasks with high precision and speed. This kind of robots is designed to have a high mechanical stiffness and with powerful motors, so that the required precision and speed can be achieved. However, such designs are inherently

Variable stiffness actuators : modeling, control, and application to compliant bipedal walking

NARCIS (Netherlands)

Visser, L.C.

2013-01-01

Robots are traditionally used in factory environments, where they perform tasks with high precision and speed. This kind of robots is designed to have a high mechanical stiffness and with powerful motors, so that the required precision and speed can be achieved. However, such designs are inherently

Differences in the mechanical properties of the developing cerebral cortical proliferative zone between mice and ferrets at both the tissue and single-cell levels

Directory of Open Access Journals (Sweden)

Arata Nagasaka

2016-11-01

Full Text Available Cell-producing events in developing tissues are mechanically dynamic throughout the cell cycle. In many epithelial systems, cells are apicobasally tall, with nuclei and somata that adopt different apicobasal positions because nuclei and somata move in a cell cycle–dependent manner. This movement is apical during G2 phase and basal during G1 phase, whereas mitosis occurs at the apical surface. These movements are collectively referred to as interkinetic nuclear migration, and such epithelia are called pseudostratified. The embryonic mammalian cerebral cortical neuroepithelium is a good model for highly pseudostratified epithelia, and we previously found differences between mice and ferrets in both horizontal cellular density (greater in ferrets and nuclear/somal movements (slower during G2 and faster during G1 in ferrets. These differences suggest that neuroepithelial cells alter their nucleokinetic behavior in response to physical factors that they encounter, which may form the basis for evolutionary transitions towards more abundant brain-cell production from mice to ferrets and primates. To address how mouse and ferret neuroepithelia may differ physically in a quantitative manner, we used atomic force microscopy to determine that the vertical stiffness of their apical surface is greater in ferrets (Young’s modulus = 1700 Pa than in mice (1400 Pa. We systematically analyzed factors underlying the apical-surface stiffness through experiments to pharmacologically inhibit actomyosin or microtubules and to examine recoiling behaviors of the apical surface upon laser ablation and also through electron microscopy to observe adherens junction. We found that although both actomyosin and microtubules are partly responsible for the apical-surface stiffness, the mousestiffness was maintained even in the presence of inhibitors. We also found that the stiffness of single, dissociated neuroepithelial cells is

Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.

Science.gov (United States)

Flavin, William P; Bousset, Luc; Green, Zachary C; Chu, Yaping; Skarpathiotis, Stratos; Chaney, Michael J; Kordower, Jeffrey H; Melki, Ronald; Campbell, Edward M

2017-10-01

Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.

Coupled elasticity-diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles.

Science.gov (United States)

Wang, Jizeng; Li, Long

2015-01-06

Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity-diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand-receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand-receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Drop casting of stiffness gradients for chip integration into stretchable substrates

International Nuclear Information System (INIS)

Naserifar, Naser; LeDuc, Philip R; Fedder, Gary K

2017-01-01

Stretchable electronics have demonstrated promise within unobtrusive wearable systems in areas such as health monitoring and medical therapy. One significant question is whether it is more advantageous to develop holistic stretchable electronics or to integrate mature CMOS into stretchable electronic substrates where the CMOS process is separated from the mechanical processing steps. A major limitation with integrating CMOS is the dissimilar interface between the soft stretchable and hard CMOS materials. To address this, we developed an approach to pattern an elastomeric polymer layer with spatially varying mechanical properties around CMOS electronics to create a controllable material stiffness gradient. Our experimental approach reveals that modifying the interfaces can increase the strain failure threshold up to 30% and subsequently decreases delamination. The stiffness gradient in the polymer layer provides a safe region for electronic chips to function under a substrate tensile strain up to 150%. These results will have impacts in diverse applications including skin sensors and wearable health monitoring systems. (paper)

Study of the chemo-hydro-mechanical behavior of stiff clays in the context of radioactive waste disposal

International Nuclear Information System (INIS)

Nguyen, Xuan Phu

2013-01-01

The present research aims to understand the chemo-hydro-mechanical behavior of stiff clays through two geological formations, the Boom Clay and the Ypresian clays which are considered as possible host formations for the radioactive wastes disposal in Belgium. The volume change behavior was studied in both intact and reconstituted states, and under different conditions: under K0 and isotropic loading, under loading/unloading loops. The results show that the volume change behavior is governed by the competition between the physico-chemical effect and the mechanical effect, characterized by a threshold stress which corresponds to the swelling stress in terms of structure changes. A constitutive law was developed to capture this aspect. The permeability was determined, compared with the results in literature and correlated with the parameters as void ratio. The permeability variation with depth shows the important role of macro-pores in fluids' transfer. The volume change behavior and permeability of intact Boom Clay and Ypresian clays are also influenced by pore water chemical composition changes which modify the diffuse double layer and give rise to the aggregation of clay particles. The elastic parameters, yield curve and failure envelope of Boom Clay and Ypresian clays were identified. A conceptual elasto-plastic model was developed, accounting for the swelling effects and the competition between the physico-chemical effect and the mechanical effect. (author)

Remote Determination of Time-Dependent Stiffness of Surface-Degrading-Polymer Scaffolds Via Synchrotron-Based Imaging.

Science.gov (United States)

Bawolin, N K; Chen, X B

2017-04-01

Surface-degrading polymers have been widely used to fabricate scaffolds with the mechanical properties appropriate for tissue regeneration/repair. During their surface degradation, the material properties of polymers remain approximately unchanged, but the scaffold geometry and thus mechanical properties vary with time. This paper presents a novel method to determine the time-dependent mechanical properties, particularly stiffness, of scaffolds from the geometric changes captured by synchrotron-based imaging, with the help of finite element analysis (FEA). Three-dimensional (3D) tissue scaffolds were fabricated from surface-degrading polymers, and during their degradation, the tissue scaffolds were imaged via the synchrotron-based imaging to characterize their changing geometry. On this basis, the stiffness behavior of scaffolds was estimated from the FEA, and the results obtained were compared to the direct measurements of scaffold stiffness from the load-displacement material testing. The comparison illustrates that the Young's moduli estimated from the FEA and characterized geometry are in agreement with the ones of direct measurements. The developed method of estimating the mechanical behavior was also demonstrated effective with a nondegrading scaffold that displays the nonlinear stress-strain behavior. The in vivo monitoring of Young's modulus by morphology characterization also suggests the feasibility of characterizing experimentally the difference between in vivo and in vitro surface degradation of tissue engineering constructs.

Design, Development and Scaling Analysis of a Variable Stiffness Magnetic Torsion Spring

Directory of Open Access Journals (Sweden)

Angelo Sudano

2013-10-01

Full Text Available In this paper we report on the design, modeling, experimental testing and scaling analysis of a novel MAgnetic Variable stiffnEess spRIng-Clutch (MAVERIC device, which may be used as the elastic element of Variable Stiffness Actuators (VSAs. The device, comprising two co-axial diametrically magnetized hollow cylinders, has two degrees of freedom: a rotation of the two cylinders around the common axis and a relative translation along the same axis. For small rotations, the torque arising from the magnetic interaction of the two cylinders is almost linearly proportional to their relative rotation, as in mechanical torsion springs. In addition, the stiffness of the equivalent spring can be varied continuously from a maximum value down to exactly zero by changing the axial overlap of the two cylinders. In this way the proposed device can be used both as a clutch (i.e., perfectly compliant element and as a variable stiffness torsion spring. A prototype, designed after magnetostatic FEM simulations, has been built and experimentally characterized. The developed MAVERIC has an experimentally determined maximum transmissible torque of 109.81mNm, while the calculated maximum stiffness is 110.2mNmrad−1. The amplitude of the torque-angle characteristic can be tuned linearly with a sensitivity of 12.63mNmmm−1 rad−1. Further simulations have been computed parameterizing the geometry and the number of pole pairs of the magnets. The maximum torque density reached for one pole pair is 47.21 · 103 Nm m−3, whereas for a fixed geometry similar to that of the developed prototype, the maximum torque is reached for seven pole pairs. Overall, compared to mechanical springs, MAVERIC has no fatigue or overloading issues. Compared to other magnetic couplers, torsion stiffness can be varied continuously from a maximum value down to exactly zero, when the device acts as a disengaged clutch, disconnecting the load from the actuator.

Big bang nucleosynthesis with a stiff fluid

International Nuclear Information System (INIS)

Dutta, Sourish; Scherrer, Robert J.

2010-01-01

Models that lead to a cosmological stiff fluid component, with a density ρ S that scales as a -6 , where a is the scale factor, have been proposed recently in a variety of contexts. We calculate numerically the effect of such a stiff fluid on the primordial element abundances. Because the stiff fluid energy density decreases with the scale factor more rapidly than radiation, it produces a relatively larger change in the primordial helium-4 abundance than in the other element abundances, relative to the changes produced by an additional radiation component. We show that the helium-4 abundance varies linearly with the density of the stiff fluid at a fixed fiducial temperature. Taking ρ S10 and ρ R10 to be the stiff fluid energy density and the standard density in relativistic particles, respectively, at T=10 MeV, we find that the change in the primordial helium abundance is well-fit by ΔY p =0.00024(ρ S10 /ρ R10 ). The changes in the helium-4 abundance produced by additional radiation or by a stiff fluid are identical when these two components have equal density at a 'pivot temperature', T * , where we find T * =0.55 MeV. Current estimates of the primordial 4 He abundance give the constraint on a stiff fluid energy density of ρ S10 /ρ R10 <30.

Direct measurement of the intrinsic ankle stiffness during standing.

Science.gov (United States)

Vlutters, M; Boonstra, T A; Schouten, A C; van der Kooij, H

2015-05-01

Ankle stiffness contributes to standing balance, counteracting the destabilizing effect of gravity. The ankle stiffness together with the compliance between the foot and the support surface make up the ankle-foot stiffness, which is relevant to quiet standing. The contribution of the intrinsic ankle-foot stiffness to balance, and the ankle-foot stiffness amplitude dependency remain a topic of debate in the literature. We therefore developed an experimental protocol to directly measure the bilateral intrinsic ankle-foot stiffness during standing balance, and determine its amplitude dependency. By applying fast (40 ms) ramp-and-hold support surface rotations (0.005-0.08 rad) during standing, reflexive contributions could be excluded, and the amplitude dependency of the intrinsic ankle-foot stiffness was investigated. Results showed that reflexive activity could not have biased the torque used for estimating the intrinsic stiffness. Furthermore, subjects required less recovery action to restore balance after bilateral rotations in opposite directions compared to rotations in the same direction. The intrinsic ankle-foot stiffness appears insufficient to ensure balance, ranging from 0.93±0.09 to 0.44±0.06 (normalized to critical stiffness 'mgh'). This implies that changes in muscle activation are required to maintain balance. The non-linear stiffness decrease with increasing rotation amplitude supports the previous published research. With the proposed method reflexive effects can be ruled out from the measured torque without any model assumptions, allowing direct estimation of intrinsic stiffness during standing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential fracture healing resulting from fixation stiffness variability. A mouse model

International Nuclear Information System (INIS)

Gardner, M.J.; Putnam, S.M.; Wong, A.; Streubel, P.N.; Kotiya, A.; Silva, M.J.

2011-01-01

The mechanisms underlying the interaction between the local mechanical environment and fracture healing are not known. We developed a mouse femoral fracture model with implants of different stiffness, and hypothesized that differential fracture healing would result. Femoral shaft fractures were created in 70 mice, and were treated with an intramedullary nail made of either tungsten (Young's modulus=410 GPa) or aluminium (Young's modulus=70 GPa). Mice were then sacrificed at 2 or 5 weeks. Fracture calluses were analyzed using standard microCT, histological, and biomechanical methods. At 2 weeks, callus volume was significantly greater in the aluminium group than in the tungsten group (61.2 vs. 40.5 mm 3 , p=0.016), yet bone volume within the calluses was no different between the groups (13.2 vs. 12.3 mm 3 ). Calluses from the tungsten group were stiffer on mechanical testing (18.7 vs. 9.7 N/mm, p=0.01). The percent cartilage in the callus was 31.6% in the aluminium group and 22.9% in the tungsten group (p=0.40). At 5 weeks, there were no differences between any of the healed femora. In this study, fracture implants of different stiffness led to different fracture healing in this mouse fracture model. Fractures treated with a stiffer implant had more advanced healing at 2 weeks, but still healed by callus formation. Although this concept has been well documented previously, this particular model could be a valuable research tool to study the healing consequences of altered fixation stiffness, which may provide insight into the pathogenesis and ideal treatment of fractures and non-unions. (author)

Soft Robotic Haptic Interface with Variable Stiffness for Rehabilitation of Neurologically Impaired Hand Function

Directory of Open Access Journals (Sweden)

Frederick Sebastian

2017-12-01

Full Text Available The human hand comprises complex sensorimotor functions that can be impaired by neurological diseases and traumatic injuries. Effective rehabilitation can bring the impaired hand back to a functional state because of the plasticity of the central nervous system to relearn and remodel the lost synapses in the brain. Current rehabilitation therapies focus on strengthening motor skills, such as grasping, employ multiple objects of varying stiffness so that affected persons can experience a wide range of strength training. These devices have limited range of stiffness due to the rigid mechanisms employed in their variable stiffness actuators. This paper presents a novel soft robotic haptic device for neuromuscular rehabilitation of the hand, which is designed to offer adjustable stiffness and can be utilized in both clinical and home settings. The device eliminates the need for multiple objects by employing a pneumatic soft structure made with highly compliant materials that act as the actuator of the haptic interface. It is made with interchangeable sleeves that can be customized to include materials of varying stiffness to increase the upper limit of the stiffness range. The device is fabricated using existing 3D printing technologies, and polymer molding and casting techniques, thus keeping the cost low and throughput high. The haptic interface is linked to either an open-loop system that allows for an increased pressure during usage or closed-loop system that provides pressure regulation in accordance to the stiffness the user specifies. Preliminary evaluation is performed to characterize the effective controllable region of variance in stiffness. It was found that the region of controllable stiffness was between points 3 and 7, where the stiffness appeared to plateau with each increase in pressure. The two control systems are tested to derive relationships between internal pressure, grasping force exertion on the surface, and displacement using

Using strong nonlinearity and high-frequency vibrations to control effective mechanical stiffness

DEFF Research Database (Denmark)

Thomsen, Jon Juel

2008-01-01

the method of direct separation of motions with results of a modified multiple scales ap-proach, valid also for strong nonlinearity, the stiffening ef-fect is predicted for a generic 1-dof system, and results are tested against numerical simulation and ((it is planned)) laboratory experiments.......High-frequency excitation (HFE) can be used to change the effective stiffness of an elastic structure, and related quanti-ties such as resonance frequencies, wave speed, buckling loads, and equilibrium states. There are basically two ways to do this: By using parametrical HFE (with or without non...

Mechanical performance of dovetail joint related to the global stiffness of timber roof structures

Czech Academy of Sciences Publication Activity Database

Kunecký, Jiří; Arciszewska-Kędzior, Anna; Sebera, V.; Hasníková, Hana

2016-01-01

Roč. 49, č. 6 (2016), s. 2315-2327 ISSN 1359-5997 R&D Projects: GA MK(CZ) DF12P01OVV004 Keywords : dovetail * FEM * stiffness * carpentry joint * digital image correlation Subject RIV: AL - Art, Architecture, Cultural Heritage Impact factor: 2.607, year: 2016 http://link.springer.com/article/10.1617%2Fs11527-015-0651-1

Design of a variable-stiffness robotic hand using pneumatic soft rubber actuators

International Nuclear Information System (INIS)

Nagase, Jun-ya; Saga, Norihiko; Wakimoto, Shuichi; Satoh, Toshiyuki; Suzumori, Koichi

2011-01-01

In recent years, Japanese society has been ageing, engendering a labor shortage of young workers. Robots are therefore expected to be useful in performing tasks such as day-to-day support for elderly people. In particular, robots that are intended for use in the field of medical care and welfare are expected to be safe when operating in a human environment because they often come into contact with people. Furthermore, robots must perform various tasks such as regrasping, grasping of soft objects, and tasks using frictional force. Given these demands and circumstances, a tendon-driven robot hand with a stiffness changing finger has been developed. The finger surface stiffness can be altered by adjusting the input pressure depending on the task. Additionally, the coefficient of static friction can be altered by changing the surface stiffness merely by adjusting the input air pressure. This report describes the basic structure, driving mechanism, and basic properties of the proposed robot hand

Observed variations of monopile foundation stiffness

DEFF Research Database (Denmark)

Kallehave, Dan; Thilsted, C.L.; Diaz, Alberto Troya

2015-01-01

full-scale measurements obtained from one offshore wind turbine structure located within Horns Reef II offshore wind farm. Data are presented for a 2.5 years period and covers normal operating conditions and one larger storm event. A reduction of the pile-soil stiffness was observed during the storm...... events, followed by a complete regain to a pre-storm level when the storm subsided. In additional, no long term variations of the pile-soil stiffness was observed. The wind turbine is located in dense to very dense sand deposits.......The soil-structure stiffness of monopile foundations for offshore wind turbines has a high impact on the fatigue loading during normal operating conditions. Thus, a robust design must consider the evolution of pile-soil stiffness over the lifetime of the wind farm. This paper present and discuss...

In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Holland, Jason P; Bell, Stephen G; Wong, Luet-Lok; Dilworth, Jonathan R [Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA (United Kingdom); Giansiracusa, Jeffrey H [Department of Mathematics, Mathematical Institute, University of Oxford, 24-29 St Giles' , Oxford, OX1 3LB (United Kingdom)], E-mail: hollanj3@mskcc.org, E-mail: jasonpholland@gmail.com

2009-04-07

The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [{sup 60/62/64}Cu(II)ATSM] and [{sup 60/62/64}Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO{sub 2}-dependent in vitro cellular uptake and retention of [{sup 64}Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k{sub 1} = 9.8 {+-} 0.59 x 10{sup -4} s{sup -1} and k{sub 2} = 2.9 {+-} 0.17 x 10{sup -3} s{sup -1}), intracellular reduction (k{sub 3} = 5.2 {+-} 0.31 x 10{sup -2} s{sup -1}), reoxidation (k{sub 4} = 2.2 {+-} 0.13 mol{sup -1} dm{sup 3} s{sup -1}) and proton-mediated ligand dissociation (k{sub 5} = 9.0 {+-} 0.54 x 10{sup -5} s{sup -1}). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have

Stiff Hands

Science.gov (United States)

... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Stiff Hands Email to a friend * required fields ...

Helical growth trajectories in plant roots interacting with stiff barriers

Science.gov (United States)

Gerbode, Sharon; Noar, Roslyn; Harrison, Maria

2009-03-01

Plant roots successfully navigate heterogeneous soil environments with varying nutrient and water concentrations, as well as a variety of stiff obstacles. While it is thought that the ability of roots to penetrate into a stiff lower soil layer is important for soil erosion, little is known about how a root actually responds to a rigid interface. We have developed a laser sheet imaging technique for recording the 3D growth dynamics of plant roots interacting with stiff barriers. We find that a root encountering an angled interface does not grow in a straight line along the surface, but instead follows a helical trajectory. These experiments build on the pioneering studies of roots grown on a tilted 2D surface, which reported ``root waving,'' a similar curved pattern thought to be caused by the root's sensitivity to both gravity and the rigid surface on which it is grown. Our measurements extend these results to the more physiologically relevant case of 3D growth, where the spiral trajectory can be altered by tuning the relative strengths of the gravity and touch stimuli, providing some intuition for the physical mechanism driving it.

Abnormal pulmonary artery stiffness in pulmonary arterial hypertension: in vivo study with intravascular ultrasound.

Directory of Open Access Journals (Sweden)

Edmund M T Lau

Full Text Available BACKGROUND: There is increasing recognition that pulmonary artery stiffness is an important determinant of right ventricular (RV afterload in pulmonary arterial hypertension (PAH. We used intravascular ultrasound (IVUS to evaluate the mechanical properties of the elastic pulmonary arteries (PA in subjects with PAH, and assessed the effects of PAH-specific therapy on indices of arterial stiffness. METHOD: Using IVUS and simultaneous right heart catheterisation, 20 pulmonary segments in 8 PAH subjects and 12 pulmonary segments in 8 controls were studied to determine their compliance, distensibility, elastic modulus and stiffness index β. PAH subjects underwent repeat IVUS examinations after 6-months of bosentan therapy. RESULTS: AT BASELINE, PAH SUBJECTS DEMONSTRATED GREATER STIFFNESS IN ALL MEASURED INDICES COMPARED TO CONTROLS: compliance (1.50±0.11×10(-2 mm(2/mmHg vs 4.49±0.43×10(-2 mm(2/mmHg, p<0.0001, distensibility (0.32±0.03%/mmHg vs 1.18±0.13%/mmHg, p<0.0001, elastic modulus (720±64 mmHg vs 198±19 mmHg, p<0.0001, and stiffness index β (15.0±1.4 vs 11.0±0.7, p = 0.046. Strong inverse exponential associations existed between mean pulmonary artery pressure and compliance (r(2 = 0.82, p<0.0001, and also between mean PAP and distensibility (r(2 = 0.79, p = 0.002. Bosentan therapy, for 6-months, was not associated with any significant changes in all indices of PA stiffness. CONCLUSION: Increased stiffness occurs in the proximal elastic PA in patients with PAH and contributes to the pathogenesis RV failure. Bosentan therapy may not be effective at improving PA stiffness.

A Stewart isolator with high-static-low-dynamic stiffness struts based on negative stiffness magnetic springs

Science.gov (United States)

Zheng, Yisheng; Li, Qingpin; Yan, Bo; Luo, Yajun; Zhang, Xinong

2018-05-01

In order to improve the isolation performance of passive Stewart platforms, the negative stiffness magnetic spring (NSMS) is employed to construct high static low dynamic stiffness (HSLDS) struts. With the NSMS, the resonance frequencies of the platform can be reduced effectively without deteriorating its load bearing capacity. The model of the Stewart isolation platform with HSLDS struts is presented and the stiffness characteristic of its struts is studied firstly. Then the nonlinear dynamic model of the platform including both geometry nonlinearity and stiffness nonlinearity is established; and its simplified dynamic model is derived under the condition of small vibration. The effect of nonlinearity on the isolation performance is also evaluated. Finally, a prototype is built and the isolation performance is tested. Both simulated and experimental results demonstrate that, by using the NSMS, the resonance frequencies of the Stewart isolator are reduced and the isolation performance in all six directions is improved: the isolation frequency band is increased and extended to a lower-frequency level.

Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.

Science.gov (United States)

Stenmark, Kurt R; Fagan, Karen A; Frid, Maria G

2006-09-29

Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

Structural-mechanical model of wax crystal networks—a mesoscale cellular solid approach

International Nuclear Information System (INIS)

Miyazaki, Yukihiro; Marangoni, Alejandro G

2014-01-01

Mineral waxes are widely used materials in industrial applications; however, the relationship between structure and mechanical properties is poorly understood. In this work, mineral wax-oil networks were characterized as closed-cell cellular solids, and differences in their mechanical response predicted from structural data. The systems studied included straight-chain paraffin wax (SW)-oil mixtures and polyethylene wax (PW)-oil mixtures. Analysis of cryogenic-SEM images of wax-oil networks allowed for the determination of the length (l) and thickness (t) of the wax cell walls as a function of wax mass fraction (Φ). A linear relationship between t/l and Φ (t/l ∼ Φ 0.89 ) suggested that wax-oil networks were cellular solids of the closed-cell type. However, the scaling behavior of the elastic modulus with the volume fraction of solids did not agree with theoretical predictions, yielding the same scaling exponent, μ = 0.84, for both waxes. This scaling exponent obtained from mechanical measurements could be predicted from the scaling behavior of the effective wax cell size as a function of wax mass fraction in oil obtained by cryogenic scanning electron microscopy. Microscopy studies allowed us to propose that wax-oil networks are structured as an ensemble of close-packed spherical cells filled with oil, and that it is the links between cells that yield under simple uniaxial compression. Thus, the Young’s moduli for the links between cells in SW and PW wax systems could be estimated as E L (SW) = 2.76 × 10 9 Pa and E L (PW) = 1.64 × 10 9 Pa, respectively. The structural parameter responsible for the observed differences in the mechanical strength between the two wax-oil systems is the size of the cells. Polyethylene wax has much smaller cell sizes than the straight chain wax and thus displays a higher Young’s modulus and yield stress. (papers)

Identification of stiffness variations in supporting substances of a human canine tooth with a bracket-beam-piezoelectric sensor and its electromechanical impedance

Directory of Open Access Journals (Sweden)

Hector A. Tinoco

2017-06-01

Full Text Available In this paper, an experimental method is described to identify the stiffness variations produced by drillings done in different supporting substances of a human canine tooth. To measure the supporting substances parameters through of a canine, a sensor-actuator system was developed. The sensor-actuator device was composed of a stainless steel bracket bonded to a steel wire attached to two piezoelectric transducers, with a concentrated mass attached to the end of the wire. To excite the device, high frequency voltage (between 5 and 10 KHz was applied through the piezo-transducers, which affects the tooth by means of the vibration of the wire. High frequency mechanical vibrations allowed the appraisal of the mechanical response from the supporting substances. Mechanical responses associated with the stiffness of the support were quantified with the electrical impedance of the piezo-transducers. The device was coupled to the crown of a canine tooth simulating a condition of fixing as in the bone, the tooth was fastened by the root portion inside the supporting substance. Four supporting substances were characterized for the tests. After establishing base values of the stiffness of each supporting substance, the stiffness variations were assessed in two stages (two drillings; these were made perpendicularly to the longitudinal axis of the tooth, Results show that it is possible to assess stiffness variations with the proposed methodology as well as to quantify the stiffness differences, by means of variation indexes.

Ciona intestinalis notochord as a new model to investigate the cellular and molecular mechanisms of tubulogenesis.

Science.gov (United States)

Denker, Elsa; Jiang, Di

2012-05-01

Biological tubes are a prevalent structural design across living organisms. They provide essential functions during the development and adult life of an organism. Increasing progress has been made recently in delineating the cellular and molecular mechanisms underlying tubulogenesis. This review aims to introduce ascidian notochord morphogenesis as an interesting model system to study the cell biology of tube formation, to a wider cell and developmental biology community. We present fundamental morphological and cellular events involved in notochord morphogenesis, compare and contrast them with other more established tubulogenesis model systems, and point out some unique features, including bipolarity of the notochord cells, and using cell shape changes and cell rearrangement to connect lumens. We highlight some initial findings in the molecular mechanisms of notochord morphogenesis. Based on these findings, we present intriguing problems and put forth hypotheses that can be addressed in future studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

International Nuclear Information System (INIS)

Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

2004-01-01

A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

A novel energy-efficient rotational variable stiffness actuator

NARCIS (Netherlands)

Rao, S.; Carloni, Raffaella; Stramigioli, Stefano

This paper presents the working principle, the design and realization of a novel rotational variable stiffness actuator, whose stiffness can be varied independently of its output angular position. This actuator is energy-efficient, meaning that the stiffness of the actuator can be varied by keeping

[Russian/German contacts in discussion on cellular mechanisms of aging and lifespan (author's transl)].

Science.gov (United States)

Duplenko, J K

1980-01-01

This is a brief review of the discussions which took place in natural literature at the end of XIX, and the beginning of XX century concerning the problems of cellular mechanism of aging, animal lifespan, death of metazoa and immortality of protozoa. The participation of German and Russian natural scientists in the discussion of cardinal gerontological questions is specially considered. The close relationship between the gerontological conceptions and the evolutionary ideas is emphasized. The author has established historical continuity of the above conceptions and modern evolutionary approaches to the predetermination of species' lifespan and mechanisms of aging.

Cellular and molecular mechanisms of alcohol-induced osteopenia.

Science.gov (United States)

Luo, Zhenhua; Liu, Yao; Liu, Yitong; Chen, Hui; Shi, Songtao; Liu, Yi

2017-12-01

Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.

Biochemical and cellular mechanisms of low-dose effects

International Nuclear Information System (INIS)

Feinendegen, L.E.; Booz, J.; Muehlensiepen, H.

1988-01-01

The question of health effects from small radiation doses remains open. Individual cells, when being hit by single elemental doses - in low-dose irradiation - react acutely and temporarily by altering control of enzyme activity, as is demonstrated for the case of thymidine kinase. This response is not constant in that it provides a temporary protection of enzyme activity against a second irradiation, by a mechanism likely to be via improved detoxification of intracellular radicals. It must be considered that in the low-dose region radiation may also exert protection against other challenges involving radicals, causing a net beneficial effect by temporarily shielding the hit cell against radicals produced by metabolism. Since molecular alterations leading to late effects are considered a consequence of the initial cellular response, late effects from small radiation doses do not necessarily adhere to a linear dose-effect relationship. The reality of the linear relationship between the risk of late effects from high doses to small doses is an assumption, for setting dose limits, but it must not be taken for predicting health detriment from low doses. (author)

Mechanical characterization of disordered and anisotropic cellular monolayers

Science.gov (United States)

Nestor-Bergmann, Alexander; Johns, Emma; Woolner, Sarah; Jensen, Oliver E.

2018-05-01

We consider a cellular monolayer, described using a vertex-based model, for which cells form a spatially disordered array of convex polygons that tile the plane. Equilibrium cell configurations are assumed to minimize a global energy defined in terms of cell areas and perimeters; energy is dissipated via dynamic area and length changes, as well as cell neighbor exchanges. The model captures our observations of an epithelium from a Xenopus embryo showing that uniaxial stretching induces spatial ordering, with cells under net tension (compression) tending to align with (against) the direction of stretch, but with the stress remaining heterogeneous at the single-cell level. We use the vertex model to derive the linearized relation between tissue-level stress, strain, and strain rate about a deformed base state, which can be used to characterize the tissue's anisotropic mechanical properties; expressions for viscoelastic tissue moduli are given as direct sums over cells. When the base state is isotropic, the model predicts that tissue properties can be tuned to a regime with high elastic shear resistance but low resistance to area changes, or vice versa.

In vivo Evaluation of Patellar Tendon Stiffness in Individuals with Patellofemoral Pain Syndrome

Directory of Open Access Journals (Sweden)

Hsin-Yi Liu

2008-01-01

Full Text Available The objective of this study was to utilise an ultrasonic technique to assess the effect of patellofemoral pain syndrome (PFPS on the mechanical properties of the patellar tendon. Seven subjects with PFPS and seven matched control subjects volunteered to participate in this study. Subjects were asked to perform isometric maximal voluntary contractions of the knee extensors while their knee extension torque was monitored and the displacement of the patellar tendon was recorded with an ultrasonic system. Our results showed significantly lower tendon stiffness (by ∼30% in the PFPS subjects. Although tendon secant modulus was lower by 34% in the PFPS subjects, the difference was not statistically significant. Therefore, we conclude that the ultrasonic technique was able to detect a decrease in the structural stiffness of the patellar tendon associated with PFPS. The decrease in tendon stiffness was moderately correlated with the length of symptoms in these individuals.

Stiffness and the automatic selection of ODE codes

International Nuclear Information System (INIS)

Shampine, L.F.

1984-01-01

The author describes the basic ideas behind the most popular methods for the numerical solution of ordinary differential equations (ODEs). He takes up the qualitative behavior of solutions of ODEs and its relation ot the propagation of numerical error. Codes for ODEs are intended either for stiff problems or for non-stiff problems. The difference is explained. Users of codes do not have the information needed to recognize stiffness. A code, DEASY, which automatically recognizes stiffness and selects a suitable method is described

Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption.

Science.gov (United States)

Inouye, Joshua M; Valero-Cuevas, Francisco J

2016-02-01

Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms

Multi-fingered haptic palpation utilizing granular jamming stiffness feedback actuators

International Nuclear Information System (INIS)

Li, Min; Sareh, Sina; Seneviratne, Lakmal D; Wurdemann, Helge A; Althoefer, Kaspar; Ranzani, Tommaso; Dasgupta, Prokar

2014-01-01

This paper describes a multi-fingered haptic palpation method using stiffness feedback actuators for simulating tissue palpation procedures in traditional and in robot-assisted minimally invasive surgery. Soft tissue stiffness is simulated by changing the stiffness property of the actuator during palpation. For the first time, granular jamming and pneumatic air actuation are combined to realize stiffness modulation. The stiffness feedback actuator is validated by stiffness measurements in indentation tests and through stiffness discrimination based on a user study. According to the indentation test results, the introduction of a pneumatic chamber to granular jamming can amplify the stiffness variation range and reduce hysteresis of the actuator. The advantage of multi-fingered palpation using the proposed actuators is proven by the comparison of the results of the stiffness discrimination performance using two-fingered (sensitivity: 82.2%, specificity: 88.9%, positive predicative value: 80.0%, accuracy: 85.4%, time: 4.84 s) and single-fingered (sensitivity: 76.4%, specificity: 85.7%, positive predicative value: 75.3%, accuracy: 81.8%, time: 7.48 s) stiffness feedback. (paper)

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory.

Science.gov (United States)

Hasselmo, Michael E; Giocomo, Lisa M; Brandon, Mark P; Yoshida, Motoharu

2010-12-31

Understanding the mechanisms of episodic memory requires linking behavioral data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. Copyright © 2010 Elsevier B.V. All rights reserved.

Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.

Science.gov (United States)

Narayanan, Kannan Badri; Ali, Manaf; Barclay, Barry J; Cheng, Qiang Shawn; D'Abronzo, Leandro; Dornetshuber-Fleiss, Rita; Ghosh, Paramita M; Gonzalez Guzman, Michael J; Lee, Tae-Jin; Leung, Po Sing; Li, Lin; Luanpitpong, Suidjit; Ratovitski, Edward; Rojanasakul, Yon; Romano, Maria Fiammetta; Romano, Simona; Sinha, Ranjeet K; Yedjou, Clement; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Ryan, Elizabeth P; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Salem, Hosni K; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Kim, Seo Yun; Bisson, William H; Lowe, Leroy; Park, Hyun Ho

2015-06-01

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Cellular and Molecular Mechanisms of Immuno-suppression by Human Type 1 Regulatory T cells

Directory of Open Access Journals (Sweden)

Silvia eGregori

2012-02-01

Full Text Available The immuno-regulatory mechanisms of IL-10-producing type 1 regulatory T (Tr1 cells have been widely studied over the years. However, several recent discoveries have shed new light on the cellular and molecular mechanisms that human Tr1 cells use to control immune responses and induce tolerance. In this review we outline the well-known and newly discovered regulatory properties of human Tr1 cells and provide an in-depth comparison of the known suppressor mechanisms of Tr1 cells with FOXP3+ Treg. We also highlight the role that Tr1 cells play in promoting and maintaining tolerance in autoimmunity, allergy, and transplantation.

Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

Science.gov (United States)

Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

2016-03-01

Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

Stiffness Evolution in Frozen Sands Subjected to Stress Changes

KAUST Repository

Dai, Sheng; Santamarina, Carlos

2017-01-01

Sampling affects all soils, including frozen soils and hydrate-bearing sediments. The authors monitor the stiffness evolution of frozen sands subjected to various temperature and stress conditions using an oedometer cell instrumented with P-wave transducers. Experimental results show the stress-dependent stiffness of freshly remolded sands, the dominant stiffening effect of ice, creep after unloading, and the associated exponential decrease in stiffness with time. The characteristic time for stiffness loss during creep is of the order of tens of minutes; therefore it is inevitable that frozen soils experience sampling disturbances attributable to unloading. Slow unloading minimizes stiffness loss; conversely, fast unloading causes a pronounced reduction in stiffness probably attributable to the brittle failure of ice or ice-mineral bonding.

Stiffness Evolution in Frozen Sands Subjected to Stress Changes

KAUST Repository

Dai, Sheng

2017-04-21

Sampling affects all soils, including frozen soils and hydrate-bearing sediments. The authors monitor the stiffness evolution of frozen sands subjected to various temperature and stress conditions using an oedometer cell instrumented with P-wave transducers. Experimental results show the stress-dependent stiffness of freshly remolded sands, the dominant stiffening effect of ice, creep after unloading, and the associated exponential decrease in stiffness with time. The characteristic time for stiffness loss during creep is of the order of tens of minutes; therefore it is inevitable that frozen soils experience sampling disturbances attributable to unloading. Slow unloading minimizes stiffness loss; conversely, fast unloading causes a pronounced reduction in stiffness probably attributable to the brittle failure of ice or ice-mineral bonding.

Smoothly varying in-plane stiffness heterogeneity evaluated under uniaxial tensile stress

Science.gov (United States)

J.M. Considine; F. Pierron; K.T. Turner; P. Lava; X. Tang

2017-01-01

Identification of spatially varying stiffness is a challenging, but important, research topic in the mechanics of materials and can provide the necessary information for material suitability, damage, and process control, especially for high‐value applications. One homogeneous and 3 heterogeneous virtual field method (VFM) formulations were used to create a methodology...

Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

Science.gov (United States)

Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

2015-02-25

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Experimental Challenges to Stiffness as a Transport Paradigm

Science.gov (United States)

Luce, T. C.

2017-10-01

Transport in plasmas is treated experimentally as a relationship between gradients and fluxes in analogy to the random-walk problem. Gyrokinetic models often predict strong increases in local flux for small increases in local gradient when above a threshold, holding all other parameters fixed. This has been named `stiffness'. The radial scalelength is then expected to vary little with source strength as a result of high stiffness. To probe the role of ExB shearing on stiffness in the DIII-D tokamak, two neutral beam injection power scans in H-mode plasmas were specially crafted-one with constant, low torque and one with increasing torque. The ion heat, electron heat, and ion toroidal momentum transport do not show expected signatures of stiffness, while the ion particle transport does. The ion heat transport shows the clearest discrepancy; the normalized heat flux drops with increasing inverse ion temperature scalelength. ExB shearing affects the transport magnitude, but not the scalelength dependence. Linear gyrofluid (TGLF) and nonlinear gyrokinetic (GYRO) predictions show stiff ion heat transport around the experimental profiles. The ion temperature gradient required to match the ion heat flux with increasing auxiliary power is not correctly described by TGLF, even when parameters are varied within the experimental uncertainties. TGLF also underpredicts transport at smaller radii, but overpredicts transport at larger radii. Independent of the theory/experiment comparison, it is not clear that the theoretical definition of stiffness yields any prediction about parameter scans such as the power scans here, because the quantities that must be held fixed to quantify stiffness are varied. A survey of recent literature indicated that profile resilience is routinely attributed to stiffness, but simple model calculations show profile resilience does not imply stiffness. Taken together, these observations challenge the use of local stiffness as a paradigm for explaining

Brain tissue stiffness is a sensitive marker for acidosis.

Science.gov (United States)

Holtzmann, Kathrin; Gautier, Hélène O B; Christ, Andreas F; Guck, Jochen; Káradóttir, Ragnhildur Thóra; Franze, Kristian

2016-09-15

Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts

International Nuclear Information System (INIS)

Klemm, Anna H.; Diez, Gerold; Alonso, Jose-Luis; Goldmann, Wolfgang H.

2009-01-01

Cytoskeletal reorganization is an ongoing process when cells adhere, move or invade extracellular substrates. The cellular force generation and transmission are determined by the intactness of the actomyosin-(focal adhesion complex)-integrin connection. We investigated the intracellular course of action in mouse embryonic fibroblasts deficient in the focal adhesion proteins vinculin and focal adhesion kinase (FAK) and the nuclear matrix protein p53 using magnetic tweezer and nanoparticle tracking techniques. Results show that the lack of these proteins decrease cellular stiffness and affect cell rheological behavior. The decrease in cellular binding strength was higher in FAK- to vinculin-deficient cells, whilst p53-deficient cells showed no effect compared to wildtype cells. The intracellular cytoskeletal activity was lowest in wildtype cells, but increased in the following order when cells lacked FAK+p53 > p53 > vinculin. In summary, cell mechanical processes are differently affected by the focal adhesion proteins vinculin and FAK than by the nuclear matrix protein, p53.

Damage severity estimation from the global stiffness decrease

International Nuclear Information System (INIS)

Nitescu, C; Gillich, G R; Manescu, T; Korka, Z I; Abdel Wahab, M

2017-01-01

In actual damage detection methods, localization and severity estimation can be treated separately. The severity is commonly estimated using fracture mechanics approach, with the main disadvantage of involving empirically deduced relations. In this paper, a damage severity estimator based on the global stiffness reduction is proposed. This feature is computed from the deflections of the intact and damaged beam, respectively. The damage is always located where the bending moment achieves maxima. If the damage is positioned elsewhere on the beam, its effect becomes lower, because the stress is produced by a diminished bending moment. It is shown that the global stiffness reduction produced by a crack is the same for all beams with a similar cross-section, regardless of the boundary conditions. One mathematical relation indicating the severity and another indicating the effect of removing damage from the beam. Measurements on damaged beams with different boundary conditions and cross-sections are carried out, and the location and severity are found using the proposed relations. These comparisons prove that the proposed approach can be used to accurately compute the severity estimator. (paper)

Neural Network Optimization of Ligament Stiffnesses for the Enhanced Predictive Ability of a Patient-Specific, Computational Foot/Ankle Model.

Science.gov (United States)

Chande, Ruchi D; Wayne, Jennifer S

2017-09-01

Computational models of diarthrodial joints serve to inform the biomechanical function of these structures, and as such, must be supplied appropriate inputs for performance that is representative of actual joint function. Inputs for these models are sourced from both imaging modalities as well as literature. The latter is often the source of mechanical properties for soft tissues, like ligament stiffnesses; however, such data are not always available for all the soft tissues nor is it known for patient-specific work. In the current research, a method to improve the ligament stiffness definition for a computational foot/ankle model was sought with the greater goal of improving the predictive ability of the computational model. Specifically, the stiffness values were optimized using artificial neural networks (ANNs); both feedforward and radial basis function networks (RBFNs) were considered. Optimal networks of each type were determined and subsequently used to predict stiffnesses for the foot/ankle model. Ultimately, the predicted stiffnesses were considered reasonable and resulted in enhanced performance of the computational model, suggesting that artificial neural networks can be used to optimize stiffness inputs.

The Effect of Shoe Insole Stiffness on Leg Stiffness during Stance Phase of Running in Two Different Speeds ‎among Active Men

Directory of Open Access Journals (Sweden)

Zeinab Tazike-Lemeski

2016-08-01

Full Text Available Introduction: The effect of shoe insoles with different characteristics and in different running speeds on lower-limb stiffness is still ‎controversial. The aim of this study was to investigate the effect of two types of insoles (soft and semi-rigid in two ‎different running speeds on leg stiffness during stance phase of running among active men.‎ Materials and Methods: ‎15 male students without any background of lower extremity injury were selected. Subjects were asked to run with ‎two controlled velocities of 3.0 ± 0.2 and 5.0 ± 0.1 m/s in control and insole conditions (soft and semi-rigid on a ‎force plate, placed on the middle of 15-meter runway. The cinematics and cinetics of motion were measured and ‎calculated using 5 video cameras and one force plate. The leg stiffness was achieved via dividing the vertical ‎ground reaction force by leg compression. Two-factor repeated measures ANOVA was used to test the hypothesis at ‎the significance level of P £ 0.050.‎ Results: There was a significant difference between the two types of insoles on leg stiffness. In fact, semi-rigid insole significantly increased leg stiffness (P < 0.001. However, this discrepancy was not related to the running speed (P = 0.999. In addition, there was no significant difference between the two different speeds on leg stiffness (P = 0.632. Conclusion: It seems that the increase in shoe insole stiffness may increase the leg stiffness. Furthermore, the effect of insole ‎stiffness is not related to the running speed, and leg stiffness will remains constant in low to medium running speeds.‎

A novel approach to study effects of asymmetric stiffness on parametric instabilities of multi-rotor-system

Science.gov (United States)

Jain, Anuj Kumar; Rastogi, Vikas; Agrawal, Atul Kumar

2018-01-01

The main focus of this paper is to study effects of asymmetric stiffness on parametric instabilities of multi-rotor-system through extended Lagrangian formalism, where symmetries are broken in terms of the rotor stiffness. The complete insight of dynamic behaviour of multi-rotor-system with asymmetries is evaluated through extension of Lagrangian equation with a case study. In this work, a dynamic mathematical model of a multi-rotor-system through a novel approach of extension of Lagrangian mechanics is developed, where the system is having asymmetries due to varying stiffness. The amplitude and the natural frequency of the rotor are obtained analytically through the proposed methodology. The bond graph modeling technique is used for modeling the asymmetric rotor. Symbol-shakti® software is used for the simulation of the model. The effects of the stiffness of multi-rotor-system on amplitude and frequencies are studied using numerical simulation. Simulation results show a considerable agreement with the theoretical results obtained through extended Lagrangian formalism. It is further shown that amplitude of the rotor increases inversely the stiffness of the rotor up to a certain limit, which is also affirmed theoretically.

Strength and stiffness reduction factors for infilled frames with openings

Science.gov (United States)

Decanini, Luis D.; Liberatore, Laura; Mollaioli, Fabrizio

2014-09-01

Framed structures are usually infilled with masonry walls. They may cause a significant increase in both stiffness and strength, reducing the deformation demand and increasing the energy dissipation capacity of the system. On the other hand, irregular arrangements of the masonry panels may lead to the concentration of damage in some regions, with negative effects; for example soft story mechanisms and shear failures in short columns. Therefore, the presence of infill walls should not be neglected, especially in regions of moderate and high seismicity. To this aim, simple models are available for solid infills walls, such as the diagonal no-tension strut model, while infilled frames with openings have not been adequately investigated. In this study, the effect of openings on the strength and stiffness of infilled frames is investigated by means of about 150 experimental and numerical tests. The main parameters involved are identified and a simple model to take into account the openings in the infills is developed and compared with other models proposed by different researchers. The model, which is based on the use of strength and stiffness reduction factors, takes into account the opening dimensions and presence of reinforcing elements around the opening. An example of an application of the proposed reduction factors is also presented.

Programmable Self-Locking Origami Mechanical Metamaterials.

Science.gov (United States)

Fang, Hongbin; Chu, Shih-Cheng A; Xia, Yutong; Wang, Kon-Well

2018-04-01

Developing mechanical metamaterials with programmable properties is an emerging topic receiving wide attention. While the programmability mainly originates from structural multistability in previously designed metamaterials, here it is shown that nonflat-foldable origami provides a new platform to achieve programmability via its intrinsic self-locking and reconfiguration capabilities. Working with the single-collinear degree-4 vertex origami tessellation, it is found that each unit cell can self-lock at a nonflat configuration and, therefore, possesses wide design space to program its foldability and relative density. Experiments and numerical analyses are combined to demonstrate that by switching the deformation modes of the constituent cell from prelocking folding to postlocking pressing, its stiffness experiences a sudden jump, implying a limiting-stopper effect. Such a stiffness jump is generalized to a multisegment piecewise stiffness profile in a multilayer model. Furthermore, it is revealed that via strategically switching the constituent cells' deformation modes through passive or active means, the n-layer metamaterial's stiffness is controllable among 2 n target stiffness values. Additionally, the piecewise stiffness can also trigger bistable responses dynamically under harmonic excitations, highlighting the metamaterial's rich dynamic performance. These unique characteristics of self-locking origami present new paths for creating programmable mechanical metamaterials with in situ controllable mechanical properties. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Extracellular Environment's Effect on Cellular Processes: An In Vitro Study of Mechanical and Chemical Cues on Human Mesenchymal Stem Cells and C17.2 Neural Stem Cells

Science.gov (United States)

Casey, Meghan E.

Stem cells are widely used in the area of tissue engineering. The ability of cells to interact with materials on the nano- and micro- level is important in the success of the biomaterial. It is well-known that cells respond to their micro- and nano-environments through a process termed chemo-mechanotransduction. It is important to establish standard protocols for cellular experiments, as chemical modifications to maintenance environments can alter long-term research results. In this work, the effects of different media compositions on human mesenchymal stem cells (hMSCs) throughout normal in vitro maintenance are investigated. Changes in RNA regulation, protein expression and proliferation are studied via quantitative polymerase chain reaction (qPCR), immunocytochemistry (ICC) and cell counts, respectively. Morphological differences are also observed throughout the experiment. Results of this study illustrate the dynamic response of hMSC maintenance to differences in growth medium and passage number. These experiments highlight the effect growth medium has on in vitro experiments and the need of consistent protocols in hMSC research. A substantial opportunity exists in neuronal research to develop a material platform that allows for both the proliferation and differentiation of stem cells into neurons and the ability to quantify the secretome of neuronal cells. Anodic aluminum oxide (AAO) membranes are fabricated in a two-step anodization procedure where voltage is varied to control the pore size and morphology of the membranes. C17.2 neural stem cells are differentiated on the membranes via serum-withdrawal. Cellular growth is characterized by scanning electron microscopy (SEM), ICC and qPCR. ImageJ software is used to obtain phenotypic cell counts and neurite outgrowth lengths. Results indicate a highly tunable correlation between AAO nanopore sizes and differentiated cell populations. By selecting AAO membranes with specific pore size ranges, control of neuronal

Cellular Mechanisms Underlying Behavioral State-Dependent Bidirectional Modulation of Motor Cortex Output

Directory of Open Access Journals (Sweden)

Julia Schiemann

2015-05-01

Full Text Available Neuronal activity in primary motor cortex (M1 correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1 a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons, and (2 a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.

High dynamic stiffness mechanical structures with nanostructured composite coatings deposited by high power impulse magnetron sputtering

Czech Academy of Sciences Publication Activity Database

Fu, Q.; Lorite, G.S.; Rashid, M.M.U.; Neuhaus, G.; Čada, Martin; Hubička, Zdeněk; Pitkänen, O.; Selkälä, T.; Uusitalo, J.; Glanz, C.; Kolaric, I.; Kordas, G.; Nicolescu, C.M.; Toth, G.

2016-01-01

Roč. 98, Mar (2016), 24-33 ISSN 0008-6223 EU Projects: European Commission(XE) 608800 - HIPPOCAMP Institutional support: RVO:68378271 Keywords : stiffness * HiPIMS * CuCN * loss modulus Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 6.337, year: 2016

Ultrasound elastography: the new frontier in direct measurement of muscle stiffness.

Science.gov (United States)

Brandenburg, Joline E; Eby, Sarah F; Song, Pengfei; Zhao, Heng; Brault, Jeffrey S; Chen, Shigao; An, Kai-Nan

2014-11-01

The use of brightness-mode ultrasound and Doppler ultrasound in physical medicine and rehabilitation has increased dramatically. The continuing evolution of ultrasound technology has also produced ultrasound elastography, a cutting-edge technology that can directly measure the mechanical properties of tissue, including muscle stiffness. Its real-time and direct measurements of muscle stiffness can aid the diagnosis and rehabilitation of acute musculoskeletal injuries and chronic myofascial pain. It can also help monitor outcomes of interventions affecting muscle in neuromuscular and musculoskeletal diseases, and it can better inform the functional prognosis. This technology has implications for even broader use of ultrasound in physical medicine and rehabilitation practice, but more knowledge about its uses and limitations is essential to its appropriate clinical implementation. In this review, we describe different ultrasound elastography techniques for studying muscle stiffness, including strain elastography, acoustic radiation force impulse imaging, and shear-wave elastography. We discuss the basic principles of these techniques, including the strengths and limitations of their measurement capabilities. We review the current muscle research, discuss physiatric clinical applications of these techniques, and note directions for future research. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cosserat modeling of cellular solids

NARCIS (Netherlands)

Onck, P.R.

Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

Science.gov (United States)

Kurdi, Ahmed T; Glavey, Siobhan V; Bezman, Natalie A; Jhatakia, Amy; Guerriero, Jennifer L; Manier, Salomon; Moschetta, Michele; Mishima, Yuji; Roccaro, Aldo; Detappe, Alexandre; Liu, Chia-Jen; Sacco, Antonio; Huynh, Daisy; Tai, Yu-Tzu; Robbins, Michael D; Azzi, Jamil; Ghobrial, Irene M

2018-04-13

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcγR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Copyright ©2018, American Association for Cancer Research.

Zeno's paradox in quantum cellular automata

Energy Technology Data Exchange (ETDEWEB)

Groessing, G [Atominst. der Oesterreichischen Universitaeten, Vienna (Austria); Zeilinger, A [Inst. fuer Experimentalphysik, Univ. Innsbruck (Austria)

1991-07-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.).

Zeno's paradox in quantum cellular automata

International Nuclear Information System (INIS)

Groessing, G.; Zeilinger, A.

1991-01-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.)

The stable stiffness triangle - drained sand during deformation cycles

DEFF Research Database (Denmark)

Sabaliauskas, Tomas; Ibsen, Lars Bo

2017-01-01

Cyclic, drained sand stiffness was observed using the Danish triaxial appa- ratus. New, deformation dependant soil property (the stable stiffness triangle) was detected. Using the the stable stiffness triangle, secant stiffness of drained sand was plausible to predict (and control) even during ir...... findings can find application in off-shore, seismic and other engi- neering practice, or inspire new branches of research and modelling wherever dynamic, cyclic or transient loaded sand is encountered....

Matrix rigidity regulates cancer cell growth and cellular phenotype.

Directory of Open Access Journals (Sweden)

Robert W Tilghman

2010-09-01

Full Text Available The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness of the microenvironment and how this response varies among cancer cell lines.In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased, and "rigidity independent" (those which grow equally on both soft and stiff substrates. Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug.These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models.

Matrix Rigidity Regulates Cancer Cell Growth and Cellular Phenotype

Science.gov (United States)

Tilghman, Robert W.; Cowan, Catharine R.; Mih, Justin D.; Koryakina, Yulia; Gioeli, Daniel; Slack-Davis, Jill K.; Blackman, Brett R.; Tschumperlin, Daniel J.; Parsons, J. Thomas

2010-01-01

Background The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness) of the microenvironment and how this response varies among cancer cell lines. Methodology/Principal Findings In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: “rigidity dependent” (those which show an increase in cell growth as extracellular rigidity is increased), and “rigidity independent” (those which grow equally on both soft and stiff substrates). Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug. Conclusions/Significance These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models. PMID:20886123

Impact attenuation properties of jazz shoes alter lower limb joint stiffness during jump landings.

Science.gov (United States)

Fong Yan, Alycia; Smith, Richard M; Hiller, Claire E; Sinclair, Peter J

2017-05-01

To quantify the impact attenuation properties of the jazz shoes, and to investigate the in-vivo effect of four jazz shoe designs on lower limb joint stiffness during a dance-specific jump. Repeated measures. A custom-built mechanical shoe tester similar to that used by athletic shoe companies was used to vertically impact the forefoot and heel region of four different jazz shoe designs. Additionally, dancers performed eight sautés in second position in bare feet and the shoe conditions. Force platforms and 3D-motion capture were used to analyse the joint stiffness of the midfoot, ankle, knee and hip during the jump landings. Mechanical testing of the jazz shoes revealed significant differences in impact attenuation characteristics among each of the jazz shoe designs. Gross knee and midfoot joint stiffness were significantly affected by the jazz shoe designs in the dancers' jump landings. The tested jazz shoe designs altered the impact attenuating capacity of jump landing technique in dancers. The cushioned jazz shoes are recommended particularly for injured dancers to reduce impact on the lower limb. Jazz shoe design should consider the impact attenuation properties of the forefoot region, due to the toe-strike landing technique in dance movement. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Pipe elbow stiffness coefficients including shear and bend flexibility factors for use in direct stiffness codes

International Nuclear Information System (INIS)

Perry, R.F.

1977-01-01

Historically, developments of computer codes used for piping analysis were based upon the flexibility method of structural analysis. Because of the specialized techniques employed in this method, the codes handled systems composed of only piping elements. Over the past ten years, the direct stiffness method has gained great popularity because of its systematic solution procedure regardless of the type of structural elements composing the system. A great advantage is realized with a direct stiffness code that combines piping elements along with other structural elements such as beams, plates, and shells, in a single model. One common problem, however, has been the lack of an accurate pipe elbow element that would adequately represent the effects of transverse shear and bend flexibility factors. The purpose of the present paper is to present a systematic derivation of the required 12x12 stiffness matrix and load vectors for a three dimensional pipe elbow element which includes the effects of transverse shear and pipe bend flexibility according to the ASME Boiler and Pressure Vessel Code, Section III. The results are presented analytically and as FORTRAN subroutines to be directly incorporated into existing direct stiffness codes. (Auth.)

The effect of Nordic hamstring strength training on muscle architecture, stiffness, and strength.

Science.gov (United States)

Seymore, Kayla D; Domire, Zachary J; DeVita, Paul; Rider, Patrick M; Kulas, Anthony S

2017-05-01

Hamstring strain injury is a frequent and serious injury in competitive and recreational sports. While Nordic hamstring (NH) eccentric strength training is an effective hamstring injury-prevention method, the protective mechanism of this exercise is not understood. Strength training increases muscle strength, but also alters muscle architecture and stiffness; all three factors may be associated with reducing muscle injuries. The purpose of this study was to examine the effects of NH eccentric strength training on hamstring muscle architecture, stiffness, and strength. Twenty healthy participants were randomly assigned to an eccentric training group or control group. Control participants performed static stretching, while experimental participants performed static stretching and NH training for 6 weeks. Pre- and post-intervention measurements included: hamstring muscle architecture and stiffness using ultrasound imaging and elastography, and maximal hamstring strength measured on a dynamometer. The experimental group, but not the control group, increased volume (131.5 vs. 145.2 cm 3 , p hamstring strength. The NH intervention was an effective training method for muscle hypertrophy, but, contrary to common literature findings for other modes of eccentric training, did not increase fascicle length. The data suggest that the mechanism behind NH eccentric strength training mitigating hamstring injury risk could be increasing volume rather than increasing muscle length. Future research is, therefore, warranted to determine if muscle hypertrophy induced by NH training lowers future hamstring strain injury risk.

Characterizing the Mechanical Properties of Running-Specific Prostheses

Science.gov (United States)

Beck, Owen N.; Taboga, Paolo; Grabowski, Alena M.

2016-01-01

The mechanical stiffness of running-specific prostheses likely affects the functional abilities of athletes with leg amputations. However, each prosthetic manufacturer recommends prostheses based on subjective stiffness categories rather than performance based metrics. The actual mechanical stiffness values of running-specific prostheses (i.e. kN/m) are unknown. Consequently, we sought to characterize and disseminate the stiffness values of running-specific prostheses so that researchers, clinicians, and athletes can objectively evaluate prosthetic function. We characterized the stiffness values of 55 running-specific prostheses across various models, stiffness categories, and heights using forces and angles representative of those measured from athletes with transtibial amputations during running. Characterizing prosthetic force-displacement profiles with a 2nd degree polynomial explained 4.4% more of the variance than a linear function (prunning 3 m/s and 6 m/s (10°-25°) compared to neutral (0°) (pRunning-specific prostheses should be tested under the demands of the respective activity in order to derive relevant characterizations of stiffness and function. In all, our results indicate that when athletes with leg amputations alter prosthetic model, height, and/or sagittal plane alignment, their prosthetic stiffness profiles also change; therefore variations in comfort, performance, etc. may be indirectly due to altered stiffness. PMID:27973573

Cellular and Molecular Mechanisms in Perioperative Hepatic Protection: A Review of Current Interventions

Directory of Open Access Journals (Sweden)

Zahra Talebi

2017-05-01

Full Text Available Liver is one of the most important organs needing great concern during the perioperative period. There are a number of different mechanisms that interact with liver cells and might affect their integrity and cell live. Though these mechanisms are not all the same, there is a great common point: all affect the metabolic pathways of the liver. Ischemia, anesthetic drug effects and other perioperative insults may affect the liver. Disturbance in an organ’s blood flow is an inherent part of diverse surgical procedures, which leads to lack of oxygen and nutrient supply. These ischemic periods can be particularly long in case of liver surgeries, such as resection of large hepatic tumors, management of hepatic trauma and liver transplant. Once the blood flow and oxygen supply are restored, the interruption of blood flow affects the oxygen dependent cells in liver, which require mitochondrial oxidative phosphorylation for their metabolism. Molecular mechanisms such as Redox status, ionic interchange disturbances as well as different mediators and cells like KC, SEC, dendritic cells, leukocytes, and lymphocytes, are involved in the process ultimately leading to cell death by apoptosis and necrosis. This review provides an overview on the cellular and molecular mechanisms involved in liver injuries, categorizing these mechanisms in 3 different classes: preoperative mechanisms, intraoperative mechanisms and postoperative mechanisms. Each of them are discussed in a different part of the manuscript

Direct measurement of the intrinsic ankle stiffness during standing

NARCIS (Netherlands)

Vlutters, Mark; Vlutters, M.; Boonstra, Tjitske; Schouten, Alfred Christiaan; van der Kooij, Herman

2015-01-01

Ankle stiffness contributes to standing balance, counteracting the destabilizing effect of gravity. The ankle stiffness together with the compliance between the foot and the support surface make up the ankle-foot stiffness, which is relevant to quiet standing. The contribution of the intrinsic

Crack modelling for the assessment of stiffness loss of reinforced concrete structures under mechanical loading - determination of the permeability of the micro-cracked body

International Nuclear Information System (INIS)

Bongue Boma, M.

2007-12-01

We propose a model describing the evolution of mechanical and permeability properties of concrete under slow mechanical loading. Calling upon the theory of continua with microstructure, the kinematic of the domain is enriched by a variable characterising size and orientation of the crack field. We call upon configurational forces to deal with crack propagation and we determine the balance equations governing both strain and propagation. The geometry of the microstructure is representative of the porous media: the permeability is obtained from the resolution of Stokes equations in an elementary volume. An example has been treated: we considered simple assumptions (uniform crack field, application of linear fracture mechanics...) and we determined the behaviour of a body under tensile loading. Strain, crack propagation and stiffness loss are completely assessed. Finally the evolution of permeability is plotted: once activated, crack propagation is the main cause of water tightness loss. (author)

Operator-Based Preconditioning of Stiff Hyperbolic Systems

International Nuclear Information System (INIS)

Reynolds, Daniel R.; Samtaney, Ravi; Woodward, Carol S.

2009-01-01

We introduce an operator-based scheme for preconditioning stiff components encountered in implicit methods for hyperbolic systems of partial differential equations posed on regular grids. The method is based on a directional splitting of the implicit operator, followed by a characteristic decomposition of the resulting directional parts. This approach allows for solution to any number of characteristic components, from the entire system to only the fastest, stiffness-inducing waves. We apply the preconditioning method to stiff hyperbolic systems arising in magnetohydro- dynamics and gas dynamics. We then present numerical results showing that this preconditioning scheme works well on problems where the underlying stiffness results from the interaction of fast transient waves with slowly-evolving dynamics, scales well to large problem sizes and numbers of processors, and allows for additional customization based on the specific problems under study

Biomechanics of hair cell kinocilia: experimental measurement of kinocilium shaft stiffness and base rotational stiffness with Euler–Bernoulli and Timoshenko beam analysis

Science.gov (United States)

Spoon, Corrie; Grant, Wally

2011-01-01

Vestibular hair cell bundles in the inner ear contain a single kinocilium composed of a 9+2 microtubule structure. Kinocilia play a crucial role in transmitting movement of the overlying mass, otoconial membrane or cupula to the mechanotransducing portion of the hair cell bundle. Little is known regarding the mechanical deformation properties of the kinocilium. Using a force-deflection technique, we measured two important mechanical properties of kinocilia in the utricle of a turtle, Trachemys (Pseudemys) scripta elegans. First, we measured the stiffness of kinocilia with different heights. These kinocilia were assumed to be homogenous cylindrical rods and were modeled as both isotropic Euler–Bernoulli beams and transversely isotropic Timoshenko beams. Two mechanical properties of the kinocilia were derived from the beam analysis: flexural rigidity (EI) and shear rigidity (kGA). The Timoshenko model produced a better fit to the experimental data, predicting EI=10,400 pN μm2 and kGA=247 pN. Assuming a homogenous rod, the shear modulus (G=1.9 kPa) was four orders of magnitude less than Young's modulus (E=14.1 MPa), indicating that significant shear deformation occurs within deflected kinocilia. When analyzed as an Euler–Bernoulli beam, which neglects translational shear, EI increased linearly with kinocilium height, giving underestimates of EI for shorter kinocilia. Second, we measured the rotational stiffness of the kinocilium insertion (κ) into the hair cell's apical surface. Following BAPTA treatment to break the kinocilial links, the kinocilia remained upright, and κ was measured as 177±47 pN μm rad–1. The mechanical parameters we quantified are important for understanding how forces arising from head movement are transduced and encoded by hair cells. PMID:21307074

Experimental exposure to diesel exhaust increases arterial stiffness in man

Directory of Open Access Journals (Sweden)

Newby David E

2009-03-01

Full Text Available Abstract Introduction Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness. Methods In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3 or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA, as well as at the femoral and carotid arteries for pulse wave velocity (PWV. PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP, augmentation index (AIx and time to wave reflection (Tr were calculated. Results Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02 and in AIx of 7.8% (p = 0.01, along with a 16 ms reduction in Tr (p = 0.03, 10 minutes post-exposure. Conclusion Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.

Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

Directory of Open Access Journals (Sweden)

Michael E. Hasselmo

2008-01-01

Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

Sexual Experience in Female Rodents: Cellular Mechanisms and Functional Consequences

Science.gov (United States)

Meisel, Robert L.; Mullins, Amanda J.

2007-01-01

The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions and how sexual experience alters copulatory efficiency. This review summarizes the effects of sexual experience on reward processes and copulation in female Syrian hamsters. Neural correlates of these sexual interactions include long-term cellular changes in dopamine transmission and postsynaptic signaling pathways related to neuronal plasticity (e.g., dendritic spine formation). Taken together, these studies suggest that sexual experience enhances the reinforcing properties of sexual behavior, which has the coincident outcome of increasing copulatory efficiency in a way that can increase reproductive success. PMID:16978593

Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties

International Nuclear Information System (INIS)

Miroshnikova, Y A; Sarang-Sieminski, A L; Jorgens, D M; Auer, M; Spirio, L; Weaver, V M

2011-01-01

The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context

The study of stiffness modulus values for AC-WC pavement

Science.gov (United States)

Lubis, AS; Muis, Z. A.; Iskandar, T. D.

2018-02-01

One of the parameters of the asphalt mixture in order for the strength and durability to be achieved as required is the stress-and-strain showing the stiffness of a material. Stiffness modulus is a very necessary factor that will affect the performance of asphalt pavements. If the stiffness modulus value decreases there will be a cause of aging asphalt pavement crack easily when receiving a heavy load. The high stiffness modulus asphalt concrete causes more stiff and resistant to bending. The stiffness modulus value of an asphalt mixture material can be obtained from the theoretical (indirect methods) and laboratory test results (direct methods). For the indirect methods used Brown & Brunton method, and Shell Bitumen method; while for the direct methods used the UMATTA tool. This study aims to determine stiffness modulus values for AC-WC pavement. The tests were conducted in laboratory that used 3 methods, i.e. Brown & Brunton Method, Shell Bitumen Method and Marshall Test as a substitute tool for the UMATTA tool. Hotmix asphalt made from type AC-WC with pen 60/70 using a mixture of optimum bitumen content was 5.84% with a standard temperature variation was 60°C and several variations of temperature that were 30, 40, 50, 70 and 80°C. The stiffness modulus value results obtained from Brown & Brunton Method, Shell Bitumen Method and Marshall Test which were 1374,93 Mpa, 235,45 Mpa dan 254,96 Mpa. The stiffness modulus value decreases with increasing temperature of the concrete asphalt. The stiffness modulus value from the Bitumen Shell method and the Marshall Test has a relatively similar value.The stiffness modulus value from the Brown & Brunton method is greater than the Bitumen Shell method and the Marshall Test, but can not measure the stiffness modulus value at temperature above 80°C.

The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting

Directory of Open Access Journals (Sweden)

Ryuta Koyama

2018-05-01

Full Text Available The question of whether mossy fiber sprouting is epileptogenic has not been resolved; both sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully supported. Therefore, whether mossy fiber sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber sprouting could lead to an understanding of central nervous system (CNS network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber sprouting by discussing mainly in vitro studies.

Advanced in study of cellular and molecular mechanisms of radiation effects on central nervous system

International Nuclear Information System (INIS)

Zhang Wei; Tu Yu; Wang Lili

2008-01-01

Along with radiation treatment extensively applied, radiation injury also is valued gradually. The effect of radiation to the cellular and molecular of central nervous system (CNS) is a complicated and moderately advanced process and the mechanism is remains incompletely clear yet. Inquiring into the possible mechanism of the CNS including the injury and the restoration of neuron, neuroglia cells, endotheliocyte cell and blood-brain barrier and the molecular level of change induced by radiation, so as to provide beneficial thought for preventing and curing radiation injury clinically. Some neuroprotective strategies are also addressed in the review. (authors)

Simvastatin Ameliorates Matrix Stiffness-Mediated Endothelial Monolayer Disruption.

Directory of Open Access Journals (Sweden)

Marsha C Lampi

Full Text Available Arterial stiffening accompanies both aging and atherosclerosis, and age-related stiffening of the arterial intima increases RhoA activity and cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized the statin simvastatin could be used to attenuate RhoA activity and inhibit the deleterious effects of increased age-related matrix stiffness on endothelial barrier function. Using polyacrylamide gels with stiffnesses of 2.5, 5, and 10 kPa to mimic the physiological stiffness of young and aged arteries, endothelial cells were grown to confluence and treated with simvastatin. Our data indicate that RhoA and phosphorylated myosin light chain activity increase with matrix stiffness but are attenuated when treated with the statin. Increases in cell contractility, cell-cell junction size, and indirect measurements of intercellular tension that increase with matrix stiffness, and are correlated with matrix stiffness-dependent increases in monolayer permeability, also decrease with statin treatment. Furthermore, we report that simvastatin increases activated Rac1 levels that contribute to endothelial barrier enhancing cytoskeletal reorganization. Simvastatin, which is prescribed clinically due to its ability to lower cholesterol, alters the endothelial cell response to increased matrix stiffness to restore endothelial monolayer barrier function, and therefore, presents a possible therapeutic intervention to prevent atherogenesis initiated by age-related arterial stiffening.

Analysis of Dynamic Stiffness of Bridge Cap-Pile System

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Jinhui Chu

2018-01-01

Full Text Available In order to investigate the applicability of dynamic stiffness for bridge cap-pile system, a laboratory test was performed. A numerical model was also built for this type of system. The impact load was applied on the cap top and the dynamic stiffness was analysed. Then, the effect of the effective friction area between pile and soil was also considered. Finally, the dynamic stiffness relationship between the single pile and the cap-pile system was also compared. The results show that the dynamic stiffness is a sensitive index and can well reflect the static characteristics of the pile at the elastic stage. There is a significant positive correlation between the vertical dynamic stiffness index and bearing capacity of the cap-pile system in the similar formation environment. For the cap-pile system with four piles, the dynamic stiffness is about four times as large as the single pile between 10 and 20 Hz.

Stiff quantum polymers

OpenAIRE

Kleinert, H.

2009-01-01

At ultralow temperatures, polymers exhibit quantum behavior, which is calculated here for the second and fourth moments of the end-to-end distribution in the large-stiffness regime. The result should be measurable for polymers in wide optical traps.

Arterial Stiffness in Children: Pediatric Measurement and Considerations

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Savant, Jonathan D.; Furth, Susan L.; Meyers, Kevin E.C.

2014-01-01

Background Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. Methods There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for pediatric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). Conclusions The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure. PMID:26587447

Mechanisms of Plastic Deformation in Collagen Networks Induced by Cellular Forces.

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Ban, Ehsan; Franklin, J Matthew; Nam, Sungmin; Smith, Lucas R; Wang, Hailong; Wells, Rebecca G; Chaudhuri, Ovijit; Liphardt, Jan T; Shenoy, Vivek B

2018-01-23

Contractile cells can reorganize fibrous extracellular matrices and form dense tracts of fibers between neighboring cells. These tracts guide the development of tubular tissue structures and provide paths for the invasion of cancer cells. Here, we studied the mechanisms of the mechanical plasticity of collagen tracts formed by contractile premalignant acinar cells and fibroblasts. Using fluorescence microscopy and second harmonic generation, we quantified the collagen densification, fiber alignment, and strains that remain within the tracts after cellular forces are abolished. We explained these observations using a theoretical fiber network model that accounts for the stretch-dependent formation of weak cross-links between nearby fibers. We tested the predictions of our model using shear rheology experiments. Both our model and rheological experiments demonstrated that increasing collagen concentration leads to substantial increases in plasticity. We also considered the effect of permanent elongation of fibers on network plasticity and derived a phase diagram that classifies the dominant mechanisms of plasticity based on the rate and magnitude of deformation and the mechanical properties of individual fibers. Plasticity is caused by the formation of new cross-links if moderate strains are applied at small rates or due to permanent fiber elongation if large strains are applied over short periods. Finally, we developed a coarse-grained model for plastic deformation of collagen networks that can be employed to simulate multicellular interactions in processes such as morphogenesis, cancer invasion, and fibrosis. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Effects of Different Exercise Modes on Arterial Stiffness and Nitric Oxide Synthesis.

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Hasegawa, Natsuki; Fujie, Shumpei; Horii, Naoki; Miyamoto-Mikami, Eri; Tsuji, Katsunori; Uchida, Masataka; Hamaoka, Takafumi; Tabata, Izumi; Iemitsu, Motoyuki

2018-06-01

Aerobic training (AT) and high-intensity intermittent training (HIIT) reduce arterial stiffness, whereas resistance training (RT) induces deterioration of or no change in arterial stiffness. However, the molecular mechanism of these effects of different exercise modes remains unclear. This study aimed to clarify the difference of different exercise effects on endothelial nitric oxide synthase (eNOS) signaling pathway and arterial stiffness in rats and humans. In the animal study, forty 10-wk-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (CON), AT (treadmill running, 60 min at 30 m·min, 5 d·wk for 8 wk), RT (ladder climbing, 8-10 sets per day, 3 d·wk for 8 wk), and HIIT (14 repeats of 20-s swimming session with 10-s pause between sessions, 4 d·wk for 6 wk from 12-wk-old) groups (n = 10 in each group). In the human study, we confirmed the effects of 6-wk HIIT and 8-wk AT interventions on central arterial stiffness and plasma nitrite/nitrate level in untrained healthy young men in randomized controlled trial (HIIT, AT, and CON; n = 7 in each group). In the animal study, the effect on aortic pulse wave velocity (PWV), as an index of central arterial stiffness, after HIIT was the same as the decrease in aortic PWV and increase in arterial eNOS/Akt phosphorylation after AT, which was not changed by RT. A negative correlation between aortic PWV and eNOS phosphorylation was observed (r = -0.38, P HIIT- and AT-induced changes in carotid-femoral PWV (HIIT -115.3 ± 63.4 and AT -157.7 ± 45.7 vs CON 71.3 ± 61.1 m·s, each P HIIT may reduce central arterial stiffness via the increase in aortic nitric oxide bioavailability despite it being done in a short time and short term and has the same effects as AT.

Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.

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Chung-Yi Yang

Full Text Available Superparamagnetic iron oxide (SPIO nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2 = 0. 8048. For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

Cell volume change through water efflux impacts cell stiffness and stem cell fate

NARCIS (Netherlands)

Guo, Ming; Pegoraro, Adrian F.; Mao, Angelo; Zhou, Enhua H.; Arany, Praveen R.; Han, Yulong; Burnette, Dylan T.; Jensen, Mikkel H.; Kasza, Karen E.; Moore, Jeffrey R.; Mackintosh, Frederick C.; Fredberg, Jeffrey J.; Mooney, David J.; Lippincott-Schwartz, Jennifer; Weitz, David A.

2017-01-01

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its

Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

Directory of Open Access Journals (Sweden)

Jinfan Tian

2017-01-01

Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

Pre-clinical evaluation of the mechanical properties of a low-stiffness cement-injectable hip stem.

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Eldesouky, Ibrahim; Harrysson, Ola; Marcellin-Little, Denis J; West, Harvey; El-Hofy, Hassan

2017-11-01

In total hip arthroplasty (THA), the femoral stem can be fixed with or without bone cement. Cementless stem fixation is recommended for young and active patients as it eliminates the risk of loss of fixation at the bone-cement and cement-implant interfaces. Cementless fixation, however, suffers from a relatively high early revision rate. In the current research, a novel low-stiffness hip stem was designed, fabricated and tested. The stem design provided the option to inject biodegradable bone cement that could enhance initial stem stability. The stem was made of Ti6Al4V alloy. The proximal portion of the stem was porous, with cubic cells. The stem was fabricated using electron beam melting (EBM) technology and tested in compression and bending. Finite-element analysis was used to evaluate stem performance under a dynamic load representing a stair descending cycle and compare it to the performance of a solid stem with similar geometry. The von Mises stresses and maximum principal strains generated within the bone increased after porous stem insertion compared to solid stem insertion. The low-modulus stem tested in this study has acceptable mechanical properties and generates strain patterns in bone that appear compatible with clinical use.