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1.
Tumour metastasis in the lymphatics is a crucial step in the progression of breast cancer. The dynamics by which breast cancer cells (BCCs) travel in the lymphatics remains poorly understood. The goal of this work is to develop a model capable of predicting the shear stresses metastasising BCCs experience using numerical and experimental techniques. This paper models the fluidic transport of large particles (\(\eta =d_{\mathrm{p}}/W=0.1-0.4\) where \(d_{\mathrm{p}}\) is the particle diameter and W is the channel width) subjected to lymphatic flow conditions (\({ Re}=0.04\)), in a \(100\times 100\,\upmu \hbox {m}\) microchannel. The feasibility of using the dynamic fluid body interaction (DFBI) method to predict particle motion was assessed, and particle tracking experiments were performed. The experiments found that particle translational velocity decreased from the undisturbed fluid velocity with increasing particle size (5–14% velocity lag for \(\eta =0.1-0.3\)). DFBI simulations were found to better predict particle behaviour than theoretical predictions; however, mesh restrictions in the near-wall region (\(0.2\,\mathrm{W}>y>0.8\,\mathrm{W}\)) result in computationally expensive models. The simulations were in good agreement with the experiments (\(<12\%\) difference) across the channel (\(0.2\,\mathrm{W}\le y\le 0.8\,\mathrm{W}\)), with differences up to 25% in the near-wall region. Particles experience a range of shear stresses (0.002–0.12 Pa) and spatial shear gradients (\(0.004-0.137\,\hbox {Pa}/\upmu \hbox {m}\)) depending on their size and radial position. The predicted shear gradients are far in excess of values associated with BCC apoptosis (\(0.004-0.023\,\hbox {Pa}/\upmu \hbox {m}\)). Increasing our understanding of the shear stress magnitudes and gradients experienced by BCCs could be leveraged to elucidate whether a particular BCC size or location exists that encourages metastasis within the lymphatics.  相似文献   

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3.
Mechanical properties of a single cell and its mechanical response under stimulation play an important role in regulating interactions between cell and extracellular matrix and affecting mechanotransduction. Osteocytes exhibit solid-like viscoelastic behavior in response to the interstitial fluid shear resulting from tissue matrix deformation. This study intends to quantitatively describe the mechanical behavior of osteocytes combining in vitro experiment and fluid–structure interaction (FSI) finite element (FE) model. The cell is configured in the FSI FE model using the observed data from quasi-3D images. Instead of simply assigning the cellular viscoelastic parameters by statistical data, the mechanical parameters are determined by an iterative algorithm comparing the experimental and the computational results from the FE model. The viscoelastic parameters of osteocytes are obtained as: the equilibrium elasticity modulus \(k_{1}=0.15\pm 0.038\,\hbox {kPa}\), instantaneous elasticity modulus \((k_{1}+k_{2})=0.77\pm 0.23\,\hbox {kPa}\), viscosity coefficient \(\eta =1.38\pm 0.33\,\hbox {kPa}\,\hbox {s}\). A novel index to quantify the cell adhesion is also put forward. In addition, an interesting competition phenomenon is revealed on the cell surface concerning stress and strain, i.e., the place with high stress has low strain and that with low stress has high strain. The proposed method provides a novel technique to study the mechanical behavior of individual adherent cell in vitro. It is believed that this quantitative technique not only determines cell mechanical behavior but also helps elucidate the mechanism of mechanotransduction in various types of cells.  相似文献   

4.
In this work, we use an in-vitro mechanical test to explore the resistance of biaxially stretched vena cava tissue against deep perforation and a methodology which integrates experimental and numerical modeling to identify constitutive fracture properties of the vena cava. Six sheep vena cava were harvested just after killing, and cyclic uniaxial tension tests in longitudinal and circumferential directions and biaxial deep penetration tests were performed. After that, we use a nonlinear finite element model to simulate in vitro penetration of the cava tissue in order to fit the fracture properties under penetration of the vena cava by defining a cohesive fracture zone. An iterative process was developed in order to fit the fracture properties of the vena cava using the previously obtained experimental results. The proposed solutions were obtained with fracture energy of 0.22 or 0.33 N/mm. In comparison with the experimental data, the simulation using \(\delta _{0}=0.01\,\hbox {mm}\), \(\delta _{r}=0.35\,\hbox {mm}\), and \(K=220\, \hbox {N}/\hbox {mm}^{3}\) parameters (\(F_{\hbox {max}}=0.92\)) is in good agreement with results from penetration experiments of cava tissue. It is noticeable that the parameter estimation process of the fracture behavior is more accurate than the estimation process of the elastic behavior for the toe region of the curve.  相似文献   

5.
The present study aimed to investigate the association of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north Indian population. In the present case–control study, CAD patients (\(n = 200\)) and age-matched, sex-matched and ethnicity-matched healthy controls (\(n = 200\)) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) polymorphisms of GSTP1 gene was significantly different between cases and controls (\(P = 0.005\) and 0.024, respectively). Binary logistic regression analysis showed significant association of A/G (odds ratio (OR): 1.6, 95% CI: 1.08–2.49, \(P = 0.020\)) and G/G (OR: 3.1, 95% CI: 1.41–6.71, P \(=\) 0.005) genotypes of GSTP1 \(\hbox {g}.313\hbox {A}{\!>\!}\hbox {G}\), and C/T (OR: 5.8, 95% CI: 1.26–26.34, \(P = 0.024\)) genotype of GSTP1 \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) with CAD. The A/G and G/G genotypes of \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) and C/T genotype of \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) conferred 6.5-fold increased risk for CAD (OR: 6.5, 95% CI: 1.37–31.27, \(P = 0.018\)). Moreover, the recessive model of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) is the best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95% CI: 1.11–4.92, \(P = 0.020\)). In conclusion, statistically significant associations of GSTP1 \(\hbox {g}.313\hbox {A}{>}\hbox {G}\) (A/G, G/G) and \(\hbox {g}.341\hbox {C}{>}\hbox {T}\) (C/T) genotypes with CAD were observed.  相似文献   

6.
Aberrant NSD2 methyltransferase activity is implicated as the oncogenic driver in multiple myeloma, suggesting opportunities for novel therapeutic intervention. The methyltransferase activity of NSD2 resides in its catalytic SET domain, which is conserved among most lysine methyltransferases. Here we report the backbone \(\hbox {H}^{\mathrm{N}}\), N, C\(^{\prime }\), \(\hbox {C}^\alpha\) and side-chain \(\hbox {C}^\beta\) assignments of a 25 kDa NSD2 SET domain construct, spanning residues 991–1203. A chemical shift analysis of C\(^{\prime }\), \(\hbox {C}^\alpha\) and \(\hbox {C}^\beta\) resonances predicts a secondary structural pattern that is in agreement with homology models.  相似文献   

7.
Myocardial stiffness is a valuable clinical biomarker for the monitoring and stratification of heart failure (HF). Cardiac finite element models provide a biomechanical framework for the assessment of stiffness through the determination of the myocardial constitutive model parameters. The reported parameter intercorrelations in popular constitutive relations, however, obstruct the unique estimation of material parameters and limit the reliable translation of this stiffness metric to clinical practice. Focusing on the role of the cost function (CF) in parameter identifiability, we investigate the performance of a set of geometric indices (based on displacements, strains, cavity volume, wall thickness and apicobasal dimension of the ventricle) and a novel CF derived from energy conservation. Our results, with a commonly used transversely isotropic material model (proposed by Guccione et al.), demonstrate that a single geometry-based CF is unable to uniquely constrain the parameter space. The energy-based CF, conversely, isolates one of the parameters and in conjunction with one of the geometric metrics provides a unique estimation of the parameter set. This gives rise to a new methodology for estimating myocardial material parameters based on the combination of deformation and energetics analysis. The accuracy of the pipeline is demonstrated in silico, and its robustness in vivo, in a total of 8 clinical data sets (7 HF and one control). The mean identified parameters of the Guccione material law were \(C_1=3000\pm 1700\,\hbox {Pa}\) and \(\alpha =45\pm 25\) (\(b_f=25\pm 14\), \(b_{ft}=11\pm 6\), \(b_{t}=9\pm 5\)) for the HF cases and \(C_1=1700\,\hbox {Pa}\) and \(\alpha =15\) (\(b_f=8\), \(b_{ft}=4\), \(b_{t}=3\)) for the healthy case.  相似文献   

8.
The intervertebral disc is a complex fibro-cartilaginous material, consisting of a pressurized nucleus pulposus surrounded by the annulus fibrosus, which has an angle-ply structure. Disc injury and degeneration are noted by significant changes in tissue structure and function, which significantly alters stress distribution and disc joint stiffness. Differences in fibre orientation are thought to contribute to changes in disc torsion mechanics. Therefore, the objective of this study was to evaluate the effect of collagen fibre orientation on internal disc mechanics under compression combined with axial rotation. We developed and validated a finite element model (FEM) to delineate changes in disc mechanics due to fibre orientation from differences in material properties. FEM simulations were performed with fibres oriented at \(\pm 30^{\circ }\) throughout the disc (uniform by region and fibre layer). The initial model was validated by published experimental results for two load conditions, including \(0.48\,\hbox {MPa}\) axial compression and \(10\,\hbox {Nm}\) axial rotation. Once validated, fibre orientation was rotated by \(4^{\circ }\) or \(8^{\circ }\) towards the horizontal plane, resulting in a decrease in disc joint torsional stiffness. Furthermore, we observed that axial rotation caused a sinusoidal change in disc height and radial bulge, which may be beneficial for nutrient transport. In conclusion, including anatomically relevant fibre angles in disc joint FEMs is important for understanding stress distribution throughout the disc and will be important for understanding potential causes for disc injury. Future models will include regional differences in fibre orientation to better represent the fibre architecture of the native disc.  相似文献   

9.
Boundary conditions (BCs) and sample size affect the measured elastic properties of cancellous bone. Samples too small to be representative appear stiffer under kinematic uniform BCs (KUBCs) than under periodicity-compatible mixed uniform BCs (PMUBCs). To avoid those effects, we propose to determine the effective properties of trabecular bone using an embedded configuration. Cubic samples of various sizes (2.63, 5.29, 7.96, 10.58 and 15.87 mm) were cropped from \(\mu \hbox {CT}\) scans of femoral heads and vertebral bodies. They were converted into \(\mu \hbox {FE}\) models and their stiffness tensor was established via six uniaxial and shear load cases. PMUBCs- and KUBCs-based tensors were determined for each sample. “In situ” stiffness tensors were also evaluated for the embedded configuration, i.e. when the loads were transmitted to the samples via a layer of trabecular bone. The Zysset–Curnier model accounting for bone volume fraction and fabric anisotropy was fitted to those stiffness tensors, and model parameters \(\nu _{0}\) (Poisson’s ratio) \(E_{0}\) and \(\mu _{0}\) (elastic and shear moduli) were compared between sizes. BCs and sample size had little impact on \(\nu _{0}\). However, KUBCs- and PMUBCs-based \(E_{0}\) and \(\mu _{0}\), respectively, decreased and increased with growing size, though convergence was not reached even for our largest samples. Both BCs produced upper and lower bounds for the in situ values that were almost constant across samples dimensions, thus appearing as an approximation of the effective properties. PMUBCs seem also appropriate for mimicking the trabecular core, but they still underestimate its elastic properties (especially in shear) even for nearly orthotropic samples.  相似文献   

10.
We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)\(\hbox {HCO}_3^-\) cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral \(\hbox {Na}^+\)/H\(^+\) exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K\(^+\) and \(\hbox {Cl}^-\) channels and \(\hbox {Na}^+\)\(\hbox {HCO}_3^-\) cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, \(\hbox {Na}^+\)\(\hbox {HCO}^-_3\) cotransporters are more efficient than basolateral K\(^+\) and \(\hbox {Cl}^-\) channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular \(\hbox {Na}^+\) reabsorption, that is, to limit the net \(\hbox {Na}^+\) flux decrease during a hyposmotic challenge or the net \(\hbox {Na}^+\) flux increase during a hyperosmotic challenge.  相似文献   

11.
The castor bean tick, Ixodes ricinus (L.) (Ixodida: Ixodidae), is the principal vector of pathogens causing tick-borne encephalitis or Lyme borreliosis in Europe. It is therefore of general interest to make an estimate of the density of I. ricinus for the whole year at the beginning of the tick season. There are two necessary conditions for making a successful prediction: a long homogeneous time series of observed tick density and a clear biological relationship between environmental predictors and tick density. A 9-year time series covering the period 2009–2017 of nymphal I. ricinus flagged at monthly intervals in southern Germany has been used. With the hypothesis that I. ricinus density is triggered by the fructification of the European beech 2 years before, the mean annual temperature of the previous year, and the current mean winter temperature (December–February), a forecast of the annual nymphal tick density has been made. Therefore, a Poisson regression model was generated resulting in an explained variance of 93.4% and an error of \(\hbox {RMSE} = 21\) ticks per \(100\,\hbox {m}^2\) (annual \(\hbox {MEAN} = 260\) collected ticks/\(100\,\hbox {m}^2\)). An independent verification of the forecast for the year 2017 resulted in 187 predicted versus 180 observed nymphs per \(100\,\hbox {m}^2\). For the year 2018 a relatively high number of 443 questing I. ricinus nymphs per \(100\,\hbox {m}^2\) is forecasted, i.e., a “good” tick year.  相似文献   

12.
Respiratory viral infections are common in the general population and one of the most important causes of asthma aggravation and exacerbation. Despite many studies, it is not well understood how viral infections cause more severe symptoms and exacerbations in asthmatics. We develop a mathematical model of two types of macrophages that play complementary roles in fighting viral infection: classically \((\hbox {CA}\)-\(\hbox {M}\Phi )\) and alternatively activated macrophages \((\hbox {AA}\)-\(\hbox {M}\Phi )\). \(\hbox {CA}\)-\(\hbox {M}\Phi \) destroy infected cells and tissues to remove viruses, while \(\hbox {AA}\)-\(\hbox {M}\Phi \) repair damaged tissues. We show that a higher viral load or longer duration of infection provokes a stronger immune response from the macrophage system. By adjusting the parameters, we model the differences in response to respiratory viral infection in normal and asthmatic subjects and show how this skews the system toward a response that generates more severe symptoms in asthmatic patients.  相似文献   

13.
Identifying the best performing hybrid without a field test was essential to save resources and time. In this study, the genetic divergence was estimated using morphological and expressed sequence tag (EST)-derived simple sequence repeats (SSR) markers. Cluster analysis showed that APMS6A and RPHR 1005 belong to groups I and II, respectively, and the hybrid combination recorded the highest mean grain yield of 32.25 g among generated 40 \(\hbox {F}_{1}\hbox {s}\) with standard heterosis of 8.4% over hybrid check, KRH2. The coefficient of marker polymorphism (CMP) value was calculated based on EST-SSR markers; it ranged from 0.40 to 0.80, and a higher CMP value of 0.80 was obtained for the parental combination APMS6A \(\times \) RPHR1005. We predicted heterosis for 40 \(\hbox {F}_{1}\hbox {s}\) based on correlation between CMP and standard heterosis in different traits with standard varietal and hybrid checks indicating positive correlation and significant value for grain yield per plant (\(r=0.58\)**), productivity per day (\(r=0.54\)**), productive tillers (\(r=0.34\)*) and panicle weight (\(r=0.42\)**). This study revealed that the relationship of molecular marker heterozygosity, along with the combining ability, high mean value of different traits, grouping of parental lines based on morphological and molecular characterization is helpful to identify heterotic patterns in rice.  相似文献   

14.
A micro-finite element-based method to estimate the bone loading history based on bone architecture was recently presented in the literature. However, a thorough investigation of the parameter sensitivity and plausibility of this method to predict joint loads is still missing. The goals of this study were (1) to analyse the parameter sensitivity of the joint load predictions at one proximal femur and (2) to assess the plausibility of the results by comparing load predictions of ten proximal femora to in vivo hip joint forces measured with instrumented prostheses (available from www.orthoload.com). Joint loads were predicted by optimally scaling the magnitude of four unit loads (inclined \(-20^{\circ }\) to \(100^{\circ }\) with respect to the vertical axis) applied to micro-finite element models created from high-resolution computed tomography scans (\(30.3~\upmu \)m voxel size). Parameter sensitivity analysis was performed by varying a total of nine parameters and showed that predictions of the peak load directions (range 10\(^{\circ }\)\(30^{\circ }\)) are more robust than the predicted peak load magnitudes (range 2344.8–4689.5 N). Comparing the results of all ten femora with the in vivo loading data of ten subjects showed that peak loads are plausible both in terms of the load direction (in vivo: \(18.2\pm 2.0^{\circ }\), predicted: \(20.0^{\circ }\)) and magnitude (in vivo: \(2707.6\pm 443.3~\hbox {N}\), predicted: \(3372.2\pm 597.9~\hbox {N}\)). Overall, this study suggests that micro-finite element-based joint load predictions are both plausible and robust in terms of the predicted peak load direction, but predicted load magnitudes should be interpreted with caution.  相似文献   

15.
Changes in land use affect the terrestrial carbon stock through changes in the land cover. Research on land use and analysis of variations in carbon stock have practical applications in the optimization of land use and the mitigation of climate change effects. This study was conducted in Baixiang and Julu counties in the Taihang Piedmont by employing the trend analysis method to characterize the variation in county land use and carbon stock. The findings show that in both counties, agricultural and unused land areas decreased while built-up land area increased, and the reduction in cropland was the main reason behind the agricultural land reduction. An inflection point appeared on the cropland curves of Julu, because the cropland area decreased by 1576.97 hm\(^{2}\) from 2004 to 2006. Cropland area in Baixiang decreased from 1996 to 1998 by a total of 129.89 hm\(^{2}\) and then remained relatively stable after 1998. The total carbon storage and variation in land use in the two counties displayed similar trends. Total carbon reserves in Julu increased by 2.76 \(\times \) 10\(^{4}\) tC (carbon equivalent), while those in Baixiang decreased by 0.63 \(\times \) 10\(^{4}\) tC. Carbon stock of built-up land in Julu and Baixiang increased by 2.44 \(\times \) 10\(^{4}\) and 1.22 \(\times \) 10\(^{4}\) tC, respectively.  相似文献   

16.
Okra’s (Abelmoschus esculentus (L.) Moench) commercial cultivation is threatened in the tropics due to high incidence of yellow vein mosaic virus (YVMV) disease. Okra geneticists across the world tried to understand the inheritance pattern of YVMV disease tolerance without much success. Therefore, the inheritance pattern of YVMV disease in okra was revisited by employing six generations (\(\hbox {P}_{1}\), \(\hbox {P}_{2}\), \(\hbox {F}_{1}\), \(\hbox {F}_{2}\), \(\hbox {BC}_{1}\) and \(\hbox {BC}_{2}\)) of four selected crosses (one tolerant \(\times \) tolerant, two tolerant \(\times \) susceptible and one susceptible \(\times \) susceptible) using two tolerant (BCO-1 and Lal Bhendi) and two susceptible (Japanese Jhar Bhendi and PAN 2127) genotypes. Qualitative genetic analysis was done on the basis of segregation pattern of tolerant and susceptible plants in \(\hbox {F}_{2}\) and backcross generations of all the four crosses. It revealed that a single dominant gene along with some minor factors governed the disease tolerant trait in both the tolerant parents used. However, it was observed that genes governing disease tolerance identified in both the tolerant variety used was different. It could be concluded that the gene governing YVMV disease tolerance in okra was genotype specific. Further, duplicate gene action as evident from an approximate ratio of 15 : 1 (tolerant : susceptible) in the \(\hbox {F}_{2}\) population in the cross of two tolerant varieties gave a scope of increasing the tolerance level of the hybrid plants when both the tolerant genes are brought together. However, generation mean analysis revealed involvement of both additive and nonadditive effects in the inheritance of disease tolerance. Thus, the present study confirms that a complicated genetic inheritance pattern is involved in the disease tolerance against YVMV trait. The major tolerance genes could be transferred to other okra varieties, but the tolerance breaking virus strains might not allow them to achieve tolerance in stable condition. Therefore, accumulation of additional genes may be needed for a sustainable tolerance phenotype in okra.  相似文献   

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Most current cartilage testing devices require the preparation of excised samples and therefore do not allow intra-operative application for diagnostic purposes. The gold standard during open or arthroscopic surgery is still the subjective perception of manual palpation. This work presents a new diagnostic method of ultrasound palpation (USP) to acquire applied stress and strain data during manual palpation of articular cartilage. With the proposed method, we obtain cartilage thickness and stiffness. Moreover, repeated palpations allow the quantification of relaxation effects. USP measurements on elastomer phantoms demonstrated very good repeatability for both, stage-guided (97.2%) and handheld (96.0%) applications. The USP measurements were compared with conventional indentation experiments and revealed very good agreement on elastomer phantoms (\(r = 0.98\)) and good agreement on porcine cartilage samples (\(r = 0.76\)). Artificially degenerated cartilage samples showed reduced stiffness, weak capacity to relax after palpation and an increase of stiffness of approximately 50% with each single palpation. Intact cartilage was measured by USP directly at the patella (in situ) and after excision and removal of the subchondral bone (ex situ), leading to stiffness values of \(12.1\pm 5.5\) and \(8.5\pm 5.9\,\hbox {MPa}\) (\(p<0.05\)), respectively. The results demonstrate the potential of the USP system for cartilage testing, its sensitivity to degenerative changes and as a method for quantifying relaxation processes by means of repeated palpations. Furthermore, the differences in the results of in-situ and ex-situ measurements are of general interest, since such comparison has not been reported previously. We point out the limited comparability of ex-situ cartilage with its in-situ biomechanical behavior.  相似文献   

20.
The mechanical response of skin to external loads is influenced by anisotropy and viscoelasticity of the tissue, but the underlying mechanisms remain unclear. Here, we report a study of the main effects of tissue orientation (TO, which is linked to anisotropy) and strain rate (SR, a measure of viscoelasticity), as well as the interaction effects between the two factors, on the tensile properties of skin from a porcine model. Tensile testing to rupture of porcine skin tissue was conducted to evaluate the sensitivity of the tissue modulus of elasticity (E) and fracture-related properties, namely maximum stress \((\sigma _{U})\) and strain \((\varepsilon _{U})\) at \(\sigma _{U}\), to varying SR and TO. Specimens were excised from the abdominal skin in two orientations, namely parallel (P) and right angle (R) to the torso midline. Each TO was investigated at three SR levels, namely 0.007–0.015 \(\hbox {s}^{-1}\) (low), 0.040 \(\hbox {s}^{-1}\) (mid) and 0.065 \(\hbox {s}^{-1}\) (high). Two-factor analysis of variance revealed that the respective parameters responded differently to varying SR and TO. Significant changes in the \(\sigma _{U}\) were observed with different TOs but not with SR. The \(\varepsilon _{U}\) decreased significantly with increasing SR, but no significant variation was observed for different TOs. Significant changes in E were observed with different TOs; E increased significantly with increasing SR. More importantly, the respective mechanical parameters were not significantly influenced by interactions between SR and TO. These findings suggest that the trends associated with the changes in the skin mechanical properties may be attributed partly to differences in the anisotropy and viscoelasticity but not through any interaction between viscoelasticity and anisotropy.  相似文献   

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