Stiffness Profile Research Articles

Forward modeling of Rayleigh surface waves for analytical characterization of dominant dispersion trends

AbstractForward modeling is of critical importance for inversion analysis of surface wave methods to obtain shear‐wave velocity (VS) profiles of soil sites. The dynamic stiffness matrix (DSM) method can provide forward modeling of Rayleigh surface waves to simulate complex wave propagation in layered soil sites. However, contamination from body waves and interference of multiple Rayleigh wave modes can reduce the accuracy of theoretical dispersion curves, especially at irregular soil sites with embedded low‐velocity or high‐velocity layers. An analytical method is developed herein to combine the techniques of the multichannel analysis of surface waves method with the DSM method to improve the accuracy of the theoretical dispersion analysis for soil sites. The proposed method implements multichannel analysis of the analytical displacement responses to capture dominant dispersion trends. Comparison of the results obtained with the new method against those from the transfer matrix method and the literature indicates that the new method can (1) effectively minimize the effects of contamination caused by body waves and interference from several Rayleigh wave modes, and (2) generate accurate dominant dispersion trends for soil sites with various stiffness profiles, especially for the high‐frequency dispersion characteristics of the profiles with embedded low‐velocity layers.

Design strategy for optimizing the bandwidth of the hardening vibration generator with customized response

For popular nonlinear vibration energy harvesting systems, such as the Duffing type or the piecewise type, the stiffness profile generally follows a specific explicit expression. The response is thus determined by the coefficients of the stiffness expression and the performance trade-off between high- and low- frequency ranges always exists. To break the restriction, the non-typical nonlinear system whose stiffness profile is arbitrarily variable without an explicit expression is a promising approach. This paper proposes a novel design strategy for the hardening system to optimize the bandwidth. A customized response composed of the starting segment and the flat transition segment is firstly sketched for a target frequency range. The first segment is adopted from a linear oscillator with the rapidly increasing response while the second segment is a straight line connecting the response peak at the high cut-off frequency to the starting segment at the low-end frequency. By finding out the flattest straight line for the transition segment, the high-frequency response is ensured and the low-frequency response is maximized at the same time. Experimental tests on an elaborated prototype show that the designed generator can achieve the optimized response as desired. The superior performance due to the performance enhancement in the low-frequency range is confirmed by comparison with literature generators.

Contribution of glycosaminoglycans to the structural and mechanical properties of tendons – A multiscale study

Tendinopathy of the Achilles tendon contributes to a large range of disorders, including mechanical damage and degenerative diseases. Glycosaminoglycans (GAGs), are thought to play a role in the mechanical strength of tendons by forming cross-links between collagen molecules and allowing the transmission of forces between fibrils. This study assessed the response of GAG-depleted tendons to damage induced by fatigue loading, investigating the mechanical damage (stiffness, hysteresis and maximum load), macrostructural changes (tenocyte morphology, fiber anisotropy and waviness) assessed by confocal imaging and nanostructural changes (fibril D-periodicity length) within the same non-viable intact tendons. Changes in fiber waviness and tenocyte shape are strongly correlated to mechanical and nano-structural (D-periodicity elongation) properties in both Control and GAG-depleted tendons. This study supports firstly, the vital role GAGs play as mechanical connectors facilitating the load transfer between the fibrils and their hydrophilic role in facilitating fibril sliding. Secondly, that observed changes in tenocyte shape and fiber waviness correlate with tendon stiffness and other mechanical profiles.

Effects of confining‐pressure dependent Lame moduli on the frequency‐dependent amplification of a poro‐viscoelastic soil layer under horizontal cyclic loading

AbstractIn this paper, a series of Biot theory‐based analytical solutions are proposed to study the dynamic response of a viscoelastic two‐phase porous medium subjected to horizontal cyclic loading. To investigate the effect of material dynamic properties' depth (or confining‐pressure) dependency, two types of soil stiffness profiles are adopted, along with the constant Lame elastic and loss moduli with depth: the moduli that are linearly increasing with depth and the moduli that are nonlinearly increasing with depth. The influence of the loading frequency, retardation time (or viscous damping), and a newly introduced model parameter that expresses the effect of soil cohesion on the moduli are numerically examined. When the retardation time is small and the dynamic response is periodic, it is demonstrated that the ground surface displacement versus loading frequency is greatly affected by the Lame moduli's depth‐dependency; the peak‐to‐peak period becomes shorter and the amplitude decay tends to be minimal, considering the depth‐dependency, particularly in the linearly increasing condition with depth. In addition, the cohesion‐related parameter affects not only the periodic displacement amplitude but also the phase characteristics. Furthermore, the effect of the Lame moduli's depth‐dependency is investigated on the amplification factor distribution with depth under horizontal loading.

Innovative elastomeric shear leg mount concepts for quasi-zero stiffness isolation

Passive vibration isolation may be a cost-effective solution to isolate a supported system containing a source and/or receiver from the supporting structure. The standard linear theory suggests a low-stiffness joint to create a mobility mismatch in the transmission path, but this solution may lead to large amplitude motions in the supported system. To achieve both motion control and isolation with the same mount and without compromising either objective, an innovative, nonlinear mount concept is proposed. Taking advantage of geometric nonlinearity for large displacements, a quasi-zero stiffness is generated by exploiting the interaction between the nonlinear mechanisms that govern the motion of a number of inclined shear legs. For example, a three-regime stiffness profile is created, including a medium-stiffness preload regime, a quasi-zero stiffness isolation regime, and a high-stiffness motion control regime. This concept offers significant benefits compared with a more conventional compromise approach in that low-amplitude vibrations are exceptionally isolated while large amplitude transient motions are controlled. Illustrative computational examples will be presented to support the underlying linear and nonlinear design principles. Limiting cases will be discussed as well.

A Shift in Tissue Stiffness During Hippocampal Maturation Correlates to the Pattern of Neurogenesis and Composition of the Extracellular Matrix.

Aging changes the mechanical properties of brain tissue, such as stiffness. It has been proposed that the maintenance and differentiation of neural stem cells (NSCs) are regulated in accordance with extracellular stiffness. Neurogenesis is observed in restricted niches, including the dentate gyrus (DG) of the hippocampus, throughout mammalian lifetimes. However, profiles of tissue stiffness in the DG in comparison with the activity of NSCs from the neonatal to the matured brain have rarely been addressed so far. Here, we first applied ultrasound-based shear-wave elasticity imaging (SWEI) in living animals to assess shear modulus as in vivo brain stiffness. To complement the assay, atomic force microscopy (AFM) was utilized to determine the Young’s modulus in the hippocampus as region-specific stiffness in the brain slice. The results revealed that stiffness in the granule cell layer (GCL) and the hilus, including the subgranular zone (SGZ), increased during hippocampal maturation. We then quantified NSCs and immature neural cells in the DG with differentiation markers, and verified an overall decrease of NSCs and proliferative/immature neural cells along stages, showing that a specific profile is dependent on the subregion. Subsequently, we evaluated the amount of chondroitin sulfate proteoglycans (CSPGs), the major extracellular matrix (ECM) components in the premature brain by CS-56 immunoreactivity. We observed differential signal levels of CSPGs by hippocampal subregions, which became weaker during maturation. To address the contribution of the ECM in determining tissue stiffness, we manipulated the function of CSPGs by enzymatic digestion or supplementation with chondroitin sulfate, which resulted in an increase or decrease of stiffness in the DG, respectively. Our results illustrate that stiffness in the hippocampus shifts due to the composition of ECM, which may affect postnatal neurogenesis by altering the mechanical environment of the NSC niche.

A design strategy of bio-inspired defensive structures with stiffness programmability for reusable impact-resistance protection

As a natural defensive structure, insect cuticle exhibits fascinating impact resistance properties in their body protection due to their spatial hierarchical architecture and the stiffness distribution along their thickness designed by nature. In this study, inspired by the pattern of insect cuticle, we present a novel design strategy of graded elastic ring systems with programmable stiffness gradients to enhance the protective properties. By studying the influence of the elastic modulus, radius and thickness of rings on the impact response of the bio-inspired graded ring systems, the optimal solution of programing the stiffness gradient can be obtained. The mechanical analyses of the single-column ring systems and the bio-inspired ring array architectures with different stiffness gradients under impact loading show that both the distributions of stiffness gradients along the impact direction and the concavity and convexity of the stiffness profiles have a great influence on preventing stress wave propagation and improving impact-tolerance. Compared with convex stiffness gradients, the concave stiffness gradients significantly improve the protective properties as well as reduce the peak value of collision force applied to inner structures. In concave stiffness gradients, the results show that the bio-inspired ring array architectures with exponential (EXP) stiffness gradient have been identified to result in the minimum values of stress, collision force and impulse under impact loading. The strategy proposed in this paper greatly improves the impact resistance property and defensive effect compared with that of the case without protection. The knowledge gained from this work will inspire the designs of novel advanced reusable and lightweight protective structures with improved impact resistance capability by programming reasonable stiffness distributions.

Modeling Nonlinear-Inelastic Seismic Response of Tall Buildings with Soil–Structure Interaction

Soil-structure interaction (SSI) effects are of interest for the seismic analysis and the design of tall buildings on shallow foundations, particularly when both the structure and soil undergo inelastic demands. The objective of this paper is to evaluate the interaction of nonlinear soil-structure systems using the direct fully-coupled approach for modeling SSI. Numerical simulations of linear and nonlinear tall buildings, combined with either fixed-base conditions at the ground level or an explicit soil domain, are performed. The soil domain was modeled assuming either linear elastic isotropic or multiple yield surface plane strain continuum constitutive models. An archetype 30-story building supported on a mat foundation was modeled using nonlinear link elements to control geometry, stiffness, and strength. Structural stiffness and mass profiles were algorithmically generated to satisfy prescribed modal characteristics of tall buildings and achieve a more realistic response. The influence of nonlinear material responses for both structure and supporting soils subjected to selected earthquake time histories is quantified using drifts, accelerations, displacements, hysteretic energy, and transfer functions. Nonlinear analyses considering SSI largely influenced the computed seismic structural response presented in this paper, showing a significant decrease of the seismic demands when compared to those demands obtained with linear SSI models, which impacts the structural behavior and has practical implications in seismic-resistant designs.

Zero reflections by a 1D Acoustic Black Hole termination using thermally controlled damping

The design of lightweight and stiff structures with attractive vibration damping properties is a major issue in mechanical engineering. The insertion of Acoustic Black Holes (ABH) in a beam is a technique that consists in locally reducing its thickness at the end and coating it with a visco-elastic film. The reflection coefficient of the resulting system decreases with frequency and displays typical arches which can exactly reach zero when the amount of losses is well adjusted, reaching the critical coupling condition. However, the precise amount of added damping is very difficult to tune by using classical visco-elastic layers. It is here proposed to control it by using a thermal active system acting in a shape memory polymer (SMP). In this manner, the damping and stiffness profiles become tunable via a given thermal gradient which leads to create an enhanced ABH (eABH) that can be tuned in real time, so that the critical coupling can be reached. The objective of the paper is to demonstrate numerically and experimentally the capability of an eABH to achieve exact zero reflections using precise control of temperature gradients.

A comparison of leg stiffness in running between typically developing children and children with cerebral palsy

BackgroundLeg stiffness is important during running to increase velocity and maximise efficiency by facilitating use of the stretch-shortening cycle. Children with cerebral palsy who have neuromuscular impairments may have altered leg stiffness. The aim of this study was to describe leg stiffness during running in typically developing children and those with cerebral palsy in Gross Motor Function Classification Scale levels I and II at a range of speeds. MethodsThis cross-sectional study examined kinematic data collected from typically developing children (n = 21) and children with cerebral palsy (Gross Motor Function Classification Scale level I n = 25, Gross Motor Function Classification Scale level II n = 13) during jogging, running and sprinting. Derived variables were resultant ground reaction force, change in leg length and three-dimensional leg stiffness. Linear mixed models were developed for statistical analysis. FindingsChildren with cerebral palsy had reduced stiffness when jogging (Gross Motor Function Classification Scale level I affected t = 3.81 p < 0.01; non-affected t = 2.19 p = 0.03; Gross Motor Function Classification Scale level II affected t = 2.04 p = 0.04) and running (Gross Motor Function Classification Scale level I affected t = 3.23 p < 0.01) compared to typically developing children. Affected legs were less stiff than non-affected legs only in Gross Motor Function Classification Scale level I during running (t = 2.26 p = 0.03) and sprinting (t = 2.95 p < 0.01). InterpretationChildren with cerebral palsy have atypical leg stiffness profiles which differ according to functional classification.

Effect of different forefoot rocker radii on lower-limb joint biomechanics in healthy individuals

IntroductionPrevious studies showed that rocker shoes with a stiff forefoot rocker profile significantly reduce peak plantar flexion moment at the ankle (PFM) and peak ankle dorsiflexion (DF). Both parameters are related to Achilles tendon and Plantar Fascia unloading. The shape of an outsole with a forefoot rocker is described with multiple rocker design parameters. The aim of this research is, to determine the relation between different forefoot rocker radii on peak DF and peak PFM at a self-selected walking speed. Methods10 participants walked in standard shoes and three experimental pairs of shoes with different forefoot rocker radii. Lower extremity kinematics and kinetics were collected while walking on an instrumented treadmill at preferred walking speed and analysed with Statistical Parametric Mapping (SPM) (α = .05; post-hoc α = .05/6). ResultsPeak value analyses showed significant decreases in peak DF, peak PFM, and peak ankle power generation for the rocker conditions. No relevant significant differences were found in spatio-temporal parameters and total work at the ankle joint. SPM showed a significant decrease (% gait cycle) in DF (40–69 %), PFM (7–15 %; 41–68 %; 69–81 %), ankle power (10–15 %; 32–51 %; 55–64 %; 64–67 %; 72–80 %) and foot-to-horizontal angle (FHA) (0–4 %; 40–62 %; 92–100 %) and an increased shank-to-vertical angle (SVA) (44–84 %) for the rocker conditions. ConclusionThe results of this study suggest that rocker shoes with a proximally placed apex significantly reduce DF and PFM during the third rocker compared with control shoes. This effect is mainly explained by a change in the FHA. Smaller radii cause the largest reductions in DF and PFM, so therefore, a uniform standardisation of the forefoot rocker radius is essential.

A mapping method of dynamic response and stiffness characteristics for realizing a customized nonlinear oscillator

With nonlinear systems extensively studied for applications in vibration isolation, energy harvesting, etc., most of the studies focused on the response of the nonlinear oscillator defined by some explicit equations, namely the typical oscillator. Rare studies or approaches are devoted to the non-typical nonlinear oscillator for which the stiffness profile is possible defined by an arbitrary curve without an explicit function. This paper proposes a novel design method for both typical and non-typical monostable hardening oscillators, especially for the latter one in order to achieve some arbitrarily specified response. The key idea is to construct a series of linear equivalent oscillators to reproduce the response of the nonlinear oscillator. A trial stiffness characteristic expression of the linear equivalent oscillators has been given as a function of several particular variables. It has been verified that the linear equivalent oscillators can obtain the response for some typical nonlinear oscillators. Moreover, the method can be also used in a reversed way to identify the stiffness characteristics from a given response for either typical or non-typical systems. In particular, this parameter identification feature can be utilized to design a customized oscillator with arbitrarily specified hardening response. By constructing the linear equivalent oscillators to reproduce the desired response, the linear equivalent stiffness expression can be determined, while the customized nonlinear stiffness characteristics can be obtained accordingly. Experiments on an elaborated example have validated effectiveness of the proposed method. It shows that the mapping method can be used to determine the proper stiffness characteristics for customized hardening response beyond the scope of typical nonlinear oscillators.

Effects of tunable stiffness on the hydrodynamics and flow features of a passive pitching panel

Three-dimensional numerical simulations are carried out to study the hydrodynamic performance and flow features of a bio-inspired underwater propulsor. The propulsor is constituted by a passive pitching panel. The leading edge of the panel is prescribed under a periodic heaving motion while the panel pitches passively due to the employing of a stiffness-lumped torsional spring at the leading edge. Effects of the torsional spring stiffness have been put emphases on. A real-time tunable stiffness strategy is presented and employed in the study. We first study the passive pitching effects on the hydrodynamics and flow features of the panel using a series of constant stiffness and then we study the tunable stiffness effects using cosinusoidal curve based waveforms, in which the effects of phase difference (φ) between the stiffness profile and the oscillation motion and as well as the effects of stiffness fluctuation amplitude (Gk) are investigated, respectively. The stiffness profile beneficial for propulsion efficiency is further applied to cases with different oscillation amplitudes. A high-fidelity immersed boundary method based direct numerical simulation (DNS) solver is employed to acquire the fluid dynamics and to simulate the flow. The panel passive pitching motion is solved by coupling the DNS flow solver and the Euler rigid body dynamic equation. Results show that for the constant stiffness cases, the panel generates sinusoidal-like pitching motion, and in certain stiffness range, flexibility could benefit efficiency while holding some extent of stiffness could enhance the thrust. For the tunable stiffness cases, it is found that both the mean thrust and propulsive efficiency improved when the stiffness change is in-phase with the heaving motion (φ=0°). The largest mean thrust is found at φ=120°. The wake profile shows that in the constant stiffness cases and φ=120° case, the panel in each cycle generates a pair of elongated and twisted vortex tubes, the vortex tubes in each pair interconnected with each other and induces unprofitable interactions. While in the φ=0° case the panel generates a pair of round and closed vortex loops in each cycle and the vortex loops separated directly after they have been detached from the panel and thus avoided the unprofitable vortex interactions. The stiffness fluctuation amplitude (Gk) effects study (all employing the in-phase stiffness profile) shows that all the three tested cases (Gk=0.25G0,0.5G0,0.75G0) acquired thrust and efficiency enhancement while the Gk=0.5G0 case acquired the largest efficiency benefit and the Gk=0.75G0 case had the largest thrust. Wake profiles show entire vortex loops may not be formed when Gk is small while larger Gk may affect the arrangement of the vortex loops thus may generate unprofitable vortex interactions. The results of cases with motions with variable oscillating amplitudes (A∗) show employing the real-time altering stiffness profile (φ=0°,Gk=0.5G0) improves the propulsion performance in a certain range of A∗ (0.4≤A∗≤0.8). Results from this paper demonstrated the potential of using real-time tunable stiffness in the design of passive pitching propulsors of underwater vehicles that pursue higher performance.

The effect of variable stiffness of tuna-like fish body and fin on swimming performance

The work in this paper focuses on the examination of the effect of variable stiffness distributions on the kinematics and propulsion performance of a tuna-like swimmer. This is performed with the use of a recently developed fully coupled fluid-structure interaction solver. The two different scenarios considered in the present study are the stiffness varied along the fish body and the caudal fin, respectively. Our results show that it is feasible to replicate the similar kinematics and propulsive capability to that of the real fish via purely passive structural deformations. In addition, propulsion performance improvement is mainly dependent on the better orientation of the force near the posterior part of swimmers towards the thrust direction. Specifically, when a variable body stiffness scenario is considered, the bionic body stiffness profile results in better performance in most cases studied herein compared with a uniform stiffness commonly investigated in previous studies. Given the second scenario, where the stiffness is varied only in the spanwise direction of the tail, similar tail kinematics to that of the live scombrid fish only occurs in association with the heterocercal flexural rigidity profile. The resulting asymmetric tail conformation also yields performance improvement at intermediate stiffness in comparison to the cupping and uniform stiffness.

PISA design model for monopiles for offshore wind turbines: application to a stiff glacial clay till

Offshore wind turbines in shallow coastal waters are typically supported on monopile foundations. Although three-dimensional (3D) finite-element methods are available for the design of monopiles in this context, much of the routine design work is currently conducted using simplified one-dimensional (1D) models based on the p–y method. The p–y method was originally developed for the relatively large embedded length-to-diameter ratio (L/D) piles that are typically employed in offshore oil and gas structures. Concerns exist, however, that this analysis approach may not be appropriate for monopiles with the relatively low values of L/D that are typically adopted for offshore wind turbine structures. This paper describes a new 1D design model for monopile foundations; the model is specifically formulated for offshore wind turbine applications, although the general approach could be adopted for other applications. The model draws on the conventional p–y approach, but extends it to include additional components of soil reaction that act on the pile. The 1D model is calibrated using a set of bespoke 3D finite-element analyses of monopile performance, for pile characteristics and loading conditions that span a predefined design space. The calibrated 1D model provides results that match those obtained from the 3D finite-element calibration analysis, but at a fraction of the computational cost. Moreover, within the calibration space, the 1D model is capable of delivering high-fidelity computations of monopile performance that can be used directly for design purposes. This 1D modelling approach is demonstrated for monopiles installed in a stiff, overconsolidated glacial clay till with a typical North Sea strength and stiffness profile. Although the current form of the model has been developed for homogeneous soil and monotonic loading, it forms a basis from which extensions for soil layering and cyclic loading can be developed. The general approach can be applied to other foundation and soil–structure interaction problems, in which bespoke calibration of a simplified model can lead to more efficient design.

Soil flow mechanisms of full-flow penetrometers in layered clays through particle image velocimetry analysis in centrifuge test

This paper reports the soil flow mechanisms observed in centrifuge tests around full-flow (T-bar and ball) penetrometers in layered clays. The layered clay samples consisted of soft–stiff, stiff–soft, soft–stiff–soft, and stiff–soft–stiff soil profiles. Particle image velocimetry (PIV), also known as digital image correlation (DIC), allowed accurate resolution of the flow mechanism around the faces of the T-bar and half-ball penetrated adjacent to a transparent window. For the T-bar, overall, a full symmetrical rotational flow around the T-bar dominated the behavior. A novel “trapped cavity mechanism” was revealed in stiff clay layers, with the evolution of the trapped cavity being tracked. No soil plug was trapped at the base of the advancing T-bar regardless of penetration from stiff to soft layer or the reverse. For the ball, two key features of the soil flow mechanism were identified, including (i) a combination of vertical flow, cavity expansion type flow, and rotational flow for a fully embedded ball and (ii) a stiff soil plug trapped at the base of the ball advancing in a stiff–soft clay deposit. For both penetrometers, a squeezing mechanism mobilized as they approached a soft–stiff layer interface.

Effectiveness of a steel ring-frame for the seismic strengthening of masonry walls with new openings

The creation of new openings in masonry walls is a frequent intervention in existing buildings. Depending on their size and position, these interventions may cause a significant decrease of the wall’s original in-plane strength and stiffness, thus compromising the building seismic resistance. Therefore, in masonry buildings, strengthening techniques may be required to (i) restore as much as possible the loss of stiffness and strength, (ii) be reversible and (iii) respect the compatibility between materials, particularly in the case of historical buildings. In an attempt to comply with these requirements, engineering practitioners often introduce very stiff steel profiles forming a ring-frame inside the opening for fully restoring the stiffness and resistance without substantially increasing the building's weight. However, the effectiveness of this technique is typically quantified using linear elastic analysis and a simple sum of the flexural and shear stiffness of the masonry panels and the steel ring-frame. The present work aims to improve the knowledge and better understanding of the effectiveness of this traditional steel ring-frame technique, through experimental and numerical methods. The experimental program was designed to provide a full assessment of the effects of introducing a new door opening in brick masonry walls, from the cutting process to the application of in-plane cyclic lateral deformations. The steel ring-frame was designed using numerical tools and consisted of four profiles welded together and tied to the surrounding masonry wall by means of steel dowels dry-driven into calibrated holes of the brick. Results show that the steel ring-frame system restores the original solid wall’s in-plane strength and ductility, but not the lateral stiffness, despite the use of large steel profiles.

Specificities of phonation biomechanics in Down Syndrome children

Down Syndrome (DS) has been the aim of numerous studies, although its phonation specificities have not received much attention. DS is a genetic disorder caused by the presence of a third copy of chromosome 21, being the explanation of different behavioral and clinical anomalies: developmental disorders, hearing, speech and language impairments and neuromotor and morphological alterations of the oro-naso-pharyngeal (ONP) and laryngeal (ONL) structures. The goal of the current study is to carry on a first approach to the biomechanics of phonation in DS children from an acoustic perspective, trying to describe its specificities and to establish a link with the syndrome. A specific application designed to analyze the glottal source and its relationship to vocal fold biomechanics has been used. Nineteen biomechanical features from vocal fold dynamics have been used, related to fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, mass and stiffness profiles, unbalance, contact gaps, and tremor. On one hand, the non-normophonic corpus is composed of eight children with DS with age range between five and six years old. On the other hand, a normative or normophonic population was taken. The last group consisted of eight children with similar ages to the previous ones. The results achieved show relevant differences (p < .05) in larynx biomechanics regarding the following features: deviations in the fundamental frequency, vocal fold tension (regarding musculus vocalis), and phonation tremor. These distortions could be directly related with the neuromotor alterations known to be associated to DS and could reflect underlying factors of DS phonation features.

Acquired demyelination but not genetic developmental defects in myelination leads to brain tissue stiffness changes

Changes in axonal myelination are an important hallmark of aging and a number of neurological diseases. Demyelinated axons are impaired in their function and degenerate over time. Oligodendrocytes, the cells responsible for myelination of axons, are sensitive to mechanical properties of their environment. Growing evidence indicates that mechanical properties of demyelinating lesions are different from the healthy state and thus have the potential to affect myelinating potential of oligodendrocytes. We performed a high-resolution spatial mapping of the mechanical heterogeneity of demyelinating lesions using atomic force microscope-enabled indentation. Our results indicate that the stiffness of specific regions of mouse brain tissue is influenced by age and degree of myelination. Here we specifically demonstrate that acquired acute but not genetic demyelination leads to decreased tissue stiffness, which could influence the remyelination potential of oligodendrocytes. We also demonstrate that specific brain regions have unique ranges of stiffness in white and grey matter. Our ex vivo findings may help the design of future in vitro models to mimic the mechanical environment of the brain in healthy and diseased states. The mechanical properties of demyelinating lesions reported here may facilitate novel approaches in treating demyelinating diseases such as multiple sclerosis. Statement of SignificanceMechanical characteristics of a cell's environment can have a profound influence on its biological properties. Neuronal and glial cells are sensitive to mechanical input during development, in disease and regeneration. Sustained tensile strain can promote differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes, which are responsible for the myelination of axons. Changing myelination is an important hallmark in human aging and disease, such as multiple sclerosis. Our hypothesis is that these diseases might be characterized by altered tissue stiffness and that this has an influence on remyelination potential. Here we investigate tissue stiffness profiles of healthy, aged and disease model mice. Manipulating the tissue stiffness might be another promising approach for new treatments.

Persistent augmentation of central arterial stiffness following viral clearance by direct-acting antivirals in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with risk of cardiovascular diseases. Although direct-acting antivirals (DAA) result in rapid eradication of HCV, their long-term impact on arterial stiffness remains unclear. This study aimed to evaluate changes in parameters of central arterial stiffness from pretreatment, through sustained virological response, to one year after viral clearance. Patients with chronic HCV receiving DAA treatment were enrolled prospectively. Medical history and comorbidities of all patients were collected. Lipid profiles, liver stiffness by transient elastography and central blood pressures using pulse wave analysis of the brachial artery by cuff sphygmomanometry were measured before treatment, at viral clearance and at one year following viral clearance. Augmentation index (AIx), a parameter of aortic stiffness, was calculated as the ratio of augmentation pressure to central pulse pressure. After DAA treatment, all included patients with chronic HCV (n=102) had achieved viral clearance. Cholesterol, low-density lipoprotein (LDL) and triglyceride/high-density lipoprotein (TG/HDL) increased significantly at viral clearance and persisted at one year (all P<.001). AIx was also elevated significantly at viral clearance and persisted one year later (P<.001). Changes in AIx remained significant only in patients with increased values from baseline in either LDL (P<.01) or TG/HDL (P<.001). Central arterial stiffness and lipid profiles in patients with chronic HCV worsen immediately after viral eradication by DAA treatment and persist at one year. Worsening of lipid profiles after DAA treatment contributes to central arterial stiffness in this patient population and persists long term.