Investigating the potential for reversal of myofibroblast activation in human cardiac fibroblasts in 2D culture

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): BHF MRC Introduction Cardiac fibroblasts (cFbs) are responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signalling processes. Prolonged and excessive activation of cFbs, via stimulation by transforming growth factor β (TGF-β), causes conversion of cFbs into myofibroblasts. Myofibroblasts are believed to cause pathological cardiac remodelling and to contribute to heart failure and arrhythmias. Reversion of myofibroblasts into cFbs has been demonstrated in rodent cells; it has yet to be explored in human cells. Purpose To characterise the effects of long-term 2D standard culture on the activation status of human cFbs. To identify the potential for human myofibroblasts to dedifferentiate back to cFbs. Methods Primary human cFbs were cultured in Corning Costar flasks (Young’s modulus E = ∼3GPa) for up to 10 passages. Cells were subsequently plated onto dishes with a Young’s modulus of ∼3GPa, 25kPa and 2kPa in the presence or absence of TGF-β (10ng/ml) and/or TGF-β receptor I inhibitor SD208 (10nM) for up to 4 days. The proliferative capacity of the cells was assessed using the CyQUANT NF® assay. Cells were assessed for mRNA and protein expression of myofibroblast activation markers α-smooth muscle actin (α-SMA) and collagen-1 by qPCR and western blotting. The localised distribution of α-SMA was assessed by confocal microscopy. Results Human cardiac fibroblasts robustly expressed α-SMA. Proliferation was significantly decreased at 2kPa compared to higher Young’s moduli (mean percentage change over 2 days: 2kPa = 115.1, 25kPa = 191.4, 3GPa = 205.9, p < 0.0001). qPCR analysis revealed no significant changes in expression of myofibroblast gene markers α-SMA and collagen 1 at either ∼3GPa, 25kPa or 2kPa Young’s Moduli in the presence or absence of TGF-β treatment (median fold change (interquartile range [IQR]) versus control: TGF-β(α-SMA, 3GPa) = 1.226 (0.820); TGF-β(Collagen 1, 3GPa) = 1.636 (1.403); TGF-β(α-SMA, 25kPa) = 1.069 (7.030); TGF-β(Collagen 1, 25kPa) = 1.103 (0.411); TGF-β(α-SMA, 2kPa) = 0.800 (5.021); TGF-β(Collagen 1, 2kPa) = 1.629 (7.092); n = 2-3). These data was confirmed by western blotting (median relative protein expression (IQR) versus control: TGF-β(α-SMA, 3GPa) = 1.012 (0.500); TGF-β(Collagen 1, 3GPa) = 1.008 (1.466); TGF-β(α-SMA, 25kPa) = 1.321 (2.282); TGF-β(Collagen 1, 25kPa) = 0.944 (1.125); TGF-β(α-SMA, 2kPa) = 1.142 (0.705); TGF-β(Collagen 1, 2kPa) = 0.283 (1.127), p > 0.05; n = 2-3). TGF-β or SD208 treatment did not affect α-SMA expression when assessed by confocal microscopy. Conclusions Long-term culture of human cFbs in 2D format leads to a robust and persistent activation of myofibroblasts that is unresponsive to TGF-ß activation or inhibition. Ongoing work is focussed on investigating whether human myofibroblast de-differentiation is possible.

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Transverse Young's Moduli and Cell Shapes in Coniferous Early Wood

Holzforschung ◽

10.1515/hf.2002.001 ◽

2002 ◽

Vol 56 (1) ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

Ugai Watanabe ◽

Minoru Fujita ◽

Misato Norimoto

Keyword(s):

Young’S Modulus ◽

Young's Modulus ◽

Bending Moment ◽

Cell Models ◽

Young’S Moduli ◽

Cell Shapes ◽

The Difference ◽

Square Cells ◽

Experimental Values ◽

The Relationship

Summary The relationship between transverse Young's moduli and cell shapes in coniferous early wood was investigated using cell models constructed by two dimensional power spectrum analysis. The calculated values of tangential Young's modulus qualitatively explained the relationship between experimental values and density as well as the difference in experimental values among species. The calculated values of radial Young's modulus for the species having hexagonal cells agreed well with the experimental values, whereas, for the species having square cells, the calculated values were much larger than the experimental values. This result was ascribed to the fact that the bending moment on the radial cell wall of square cell models was calculated to be small. It is suggested that the asymmetrical shape of real wood cells or the behavior of nodes during ell deformation is an important factor in the mechanism of linear elastic deformation of wood cells.

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A study into the structure and physical properties of the Cr18Ni9-grade steel following long-term irradiation as part of the BN-600 reactor internals

Nuclear Energy and Technology ◽

10.3897/nucet.6.50863 ◽

2020 ◽

Vol 6 (1) ◽

pp. 1-6

Author(s):

Irina A. Portnykh ◽

Aleksandr V. Kozlov ◽

Valery L. Panchenko ◽

Vyacheslav S. Shikhalev

Keyword(s):

Physical Properties ◽

Young’S Modulus ◽

Structural Changes ◽

Young's Modulus ◽

Void Size ◽

Initial State ◽

Porosity Distribution ◽

Grade Steel ◽

Reactor Internals

The microstructures and physical properties of the austenitic Cr18Ni9-grade steel after 22 and 33 years of operation as part of the reactor internals were tested for assessing the conditions of the BN-600 reactor non-replaceable components (internals) and the potential of their subsequent use in predicting the reactor ultimate life. The paper presents histograms of the porosity distribution depending on the void size, in samples taken from portions that were subjected to neutron irradiation with displacement rates ranging from 1.0×10–9 to 4.3×10–8 dpa/s at temperatures from 370 to 440 °C. The elasticity characteristics were measured by resonance-type ultrasonic technique for the samples taken from the same portions of material. It was demonstrated that swelling calculated using the histograms of the porosity distribution depending on the void size has the maximum value at ~415 °C and after 33 years of irradiation reaches values of ~3%. Long-term variations of Young’s modulus demonstrate non-monotonous dependence on the damage dose. The maximum relative variation of Young’s modulus after 22 and 33 years of operation does not exceed 2% and 6%, respectively, of the values corresponding to the initial state. It was shown that along with the irradiation-induced swelling the changes in the physical properties are also affected in the process of irradiation by other structural changes and, in particular, by the formation of secondary phases. As shown by the results of the studies, operation of the BN-600 reactor internals made of Cr18Ni9-grade steel can be extended beyond 33 years of service. The comparison of the results obtained for the material after 22 and 33 years of operation contains information required for describing subsequent changes of the structure and properties of the Cr18Ni9 internals. The obtained results can be used for forecasting the reactor ultimate life within the framework of existing and developed models.

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Experimental Investigation on Mechanical Properties of In Situ Cemented Paste Backfill Containing Coal Gangue and Fly Ash

Advances in Civil Engineering ◽

10.1155/2020/7964267 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Xinguo Zhang ◽

Shichuan Zhang

Keyword(s):

Mechanical Properties ◽

Tensile Strength ◽

Fly Ash ◽

Young’S Modulus ◽

Young's Modulus ◽

Friction Angle ◽

Coal Gangue ◽

Cemented Paste Backfill ◽

Paste Backfill

Cemented paste backfill containing coal gangue and fly ash (CGFACPB) is an emerging backfill technique for coal mines that allows environmentally hazardous coal gangue and fly ash to be reused in the underground goaf. Meanwhile, CGFACPB can provide an efficient ground support and reduce the surface subsidence. Due to the difference of consolidation environment between the laboratory and the field, the mechanical properties of the cemented paste backfill vary significantly. In this paper, the core specimens were collected from an underground coal mine where the CGFACPB was used for coal mining, and the mechanical properties of the collected specimens were investigated. The cores were obtained from the underground coal mine, and then the standard cylinders or discs were prepared in laboratory. The uniaxial compressive strength (UCS), Young’s modulus, and Poisson’s ratio were determined by the compression tests, and the tensile strength was achieved by the Brazilian test. Then the internal friction angle and cohesion were calculated using the improved Mohr–Coulomb strength criterion. The results showed the development of UCS can be divided into four stages, and the final long-term stable value was about 5.1 MPa. The development of Young’s modulus had similar trend. Young’s modulus had a range from 550 MPa to 750 MPa and the mean value of 675 MPa. Poisson’s ratio gradually increased with the underground curing duration and eventually approached the stable value of 0.18. The failure type of compression samples was mainly single-sided shear failure. The development of tensile strength can be divided into two stages, and the stable value of the tensile strength was about 1.05 MPa. The development of cohesion can be divided into four stages, and the stable value was about 1.75 MPa. The stable value of the internal friction angle was about 25°. This study can provide significant references for not only the long-term stability evaluation of CGFACPB in the field but also the design of optimal recipe of the cemented paste backfill (CPB).

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Young's modulus estimation in food samples: effect of experimental parameters

Mechanics & Industry ◽

10.1051/meca/2020025 ◽

2020 ◽

Vol 21 (4) ◽

pp. 404

Author(s):

Ankita Sinha ◽

Atul Bhargav

Keyword(s):

Young’S Modulus ◽

Texture Analysis ◽

Young's Modulus ◽

Food Products ◽

Food Samples ◽

Texture Measurement ◽

Test Standards ◽

Young’S Moduli ◽

Rate Dependent ◽

Sample Shape

Texture is an important attribute in the quality assessment of processed food products. Recently, Young's modulus is identified as one of the most important indicators of food texture. However, there is much ambiguity in the literature about quantification and standards for texture analysis. In this paper, the sensitivity of Young's modulus (and thus texture) towards the applied deformation rate, sample shape and size, moisture content is studied experimentally for potato and sweet potato samples. We found that Young's moduli vary by as much as 54% depending on the rate of applied strain, indicating the need for test standards. The strain rate dependent behaviour exhibits the viscoelastic nature of the potato samples, which was further validated by stress relaxation and cyclic tests. Based on our experimental iterations and associated finding of the work, we propose the need for a standardised procedure for measuring Young's modulus and texture analysis. We expect this work to serve as a crucial step toward standardised texture measurement during thermal processing of food products.

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Heating Effects on The Young's Modulus of Films Sputtered onto Micromachined Resonators

MRS Proceedings ◽

10.1557/proc-518-33 ◽

1998 ◽

Vol 518 ◽

Cited By ~ 16

Author(s):

H. Kahn ◽

M.A. Huff ◽

A.H. Heuer

Keyword(s):

Temperature Dependence ◽

Young’S Modulus ◽

Young's Modulus ◽

Single Crystal Silicon ◽

Crystal Silicon ◽

Resonant Structures ◽

Young’S Moduli ◽

Heating Effects ◽

Sputter Deposited ◽

Dc Current

AbstractSurface-micromachined polysilicon lateral resonant structures were fabricated and used to determine the temperature dependence of the Young's modulus of the polysilicon. This is done by passing a dc current through the beams during resonance testing, resulting in Joule-heating. The temperatures are calibrated by increasing the dc current until the melting point of silicon is attained. The calculated Young's moduli agree well with reported values for single crystal silicon.In addition, metal films were sputter-deposited onto the polysilicon resonators, and similar experiments performed on the composite devices to determine the temperature dependence of the modulus of the sputtered films. Ni films demonstrate a linear decrease in Young's modulus with temperature. TiNi films demonstrate two distinct modulus values with an intermediate transition region, due to the temperature-induced reversible phase transformation exhibited by TiNi.

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EXPERIMENTAL STUDY ON COMPRESSIVE YOUNG’S MODULI AND TENSILE YOUNG’S MODULUS OF FLY ASH CONCRETE

Proceedings of International Structural Engineering and Construction ◽

10.14455/isec.res.2018.98 ◽

2018 ◽

Vol 5 (2) ◽

Author(s):

Yoichi Mimura ◽

Vanissorn Vimonsatit ◽

Yuki Watanabe ◽

Itaru Horiguchi ◽

Isamu Yoshitake

Keyword(s):

Fly Ash ◽

Young’S Modulus ◽

Young's Modulus ◽

Tangent Modulus ◽

Early Age ◽

Secant Modulus ◽

Tensile Stresses ◽

Fly Ash Concrete ◽

Young’S Moduli ◽

Initial Tangent Modulus

Initial cracks due to volume changes at an early age affect the durability of concrete structures, so numerical simulations are often conducted in order to predict cracks. Such prediction requires some mechanical properties of early age concrete. Tensile Young's modulus is directly dependent on the prediction of tensile stress and is one of the important input data for FEM analysis. However, direct tension test for tensile Young's modulus needs a unique apparatus and specimen, and such test is not suitable for evaluating Young's modulus at early ages of concrete. The present study compared tensile Young's modulus with compressive Young's moduli of Fly ash concrete. Compressive Young's moduli used in this study were secant modulus and initial tangent modulus. In addition, linear modulus taken from a regression line of a compressive stress-strain curve in the range of stresses less than the splitting tensile strength was also evaluated. It is found that the secant modulus, which is generally used as Young's modulus in Japan was clearly smaller than the tensile Young's modulus, which means that, tensile stresses evaluated using a secant modulus might be underestimated. On the other hand, linear modulus and initial tangent modulus were almost equal to the tensile Young's modulus. This result indicates that tensile stresses can be evaluated using Young's modulus obtained from a compression test with general apparatus and specimens.

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Nanosized Magnesium Oxide With Engineered Expansive Property for Enhanced Cement-System Performance

SPE Journal ◽

10.2118/180038-pa ◽

2017 ◽

Vol 22 (05) ◽

pp. 1681-1689 ◽

Cited By ~ 2

Author(s):

Narjes Jafariesfad ◽

Mette Rica Geiker ◽

Pål Skalle

Keyword(s):

Heat Treatment ◽

Young’S Modulus ◽

Magnesium Oxide ◽

Young's Modulus ◽

Oil Well ◽

Cement Slurry ◽

Expansive Agent ◽

Cement System ◽

Zonal Isolation

Summary The bulk shrinkage of cement sheaths in oil wells can result in loss of long-term zonal isolation. Expansive additives are used to mitigate bulk shrinkage. To compensate effectively for bulk shrinkage during the late plastic phase and the hardening phase of the cement system, the performance of the expansive additive needs to be regulated considering the actual cement system and placement conditions. This paper presents an introductory investigation on the potential engineering of nanosized magnesium oxide (MgO) (NM) through heat treatment for use as an expansive agent in oilwell-cement systems. In this study, the bulk shrinkage of a cement system was mitigated by introducing NM with designed reactivity to the fresh cement slurry. The reactivity of NM was controlled by heat treatment. A dilatometer with corrugated molds was used to measure the linear strain of samples cured at 40°C and atmospheric pressure. The effect of NMs differing in reactivity on tensile properties of cement systems cured for 3 days at 40°C was examined by use of the flattened Brazilian test. The reactivity of the NM played a key role in controlling the bulk shrinkage of the cement system. Addition of only 2% NM by weight of cement (BWOC) with appropriate reactivity was sufficient to maintain expansion of the cement system. Adding NM to the cement system also resulted in improved mechanical flexibility. The NM with highest reactivity caused the largest reduction in Young's modulus at 3 days and, in general, the ratio of tensile strength to Young's modulus improved through the addition of NM to the cement system. Our work demonstrates that controlling the reactivity of the additive is a promising method to mitigate bulk shrinkage of cement systems and thereby to sustain the mechanical properties of the cement sheath in the oil well at an acceptable level.

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EFFECT OF SPECIMEN SIZE ON YOUNG'S MODULUS OF ELECTRODEPOSITED Ni

Surface Review and Letters ◽

10.1142/s0218625x09012639 ◽

2009 ◽

Vol 16 (02) ◽

pp. 303-307 ◽

Cited By ~ 1

Author(s):

HONG WANG ◽

RUI LIU ◽

SHENG-PING MAO ◽

JUN TANG ◽

CONG-CHUN ZHANG ◽

...

Keyword(s):

Young’S Modulus ◽

Young's Modulus ◽

Specimen Size ◽

Young’S Moduli ◽

Different Dimensions

The Young's moduli of electrodeposited Ni with different dimensions were measured carefully in this paper. The dimensions of tensile specimens were 200, 35, or 5 μm thick and 2400, 200 or 50 μm wide. These specimens were measured with three different approaches. The measured Young's moduli of Ni decrease from 122.1 ± 4.3 to 92 ± 5.2 GPa when the thickness changes from 200 to 5 μm and width changes from 2400 to 50 μm.

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Effective Young’s Modulus of Syntactic Foams with Hollow Glass Microspheres

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.29-32.607 ◽

2010 ◽

Vol 29-32 ◽

pp. 607-612 ◽

Cited By ~ 1

Author(s):

Chang Jun He ◽

Hui Jian Li ◽

Wei Yu ◽

Xi Liang ◽

Hai Yan Peng

Keyword(s):

Young’S Modulus ◽

Young's Modulus ◽

Mechanical Analysis ◽

Particulate Composites ◽

Syntactic Foams ◽

Glass Microspheres ◽

Hollow Glass Microspheres ◽

Hollow Glass ◽

Young’S Moduli ◽

Effective Young's Moduli

. The Young’s modulus of syntactic foams were studied both the experiment and the theory. The compressive test and dynamic mechanical analysis were progressed for a few of specimens, which were made of the syntactic foams with the epoxy resin and hollow glass microspheres (HGMs). the equations for Young’s modulus of concentrated particulate composites were derived using a differential scheme of an infinitely dilute system, and were employed to prediction the Young’s modulus of syntactic foams. The computed effective Young’s moduli were compared with the experimental results, the prediction values were between the lower and upper bounds of the experimental data, and the prediction model was acceptable and can estimate the Young’s modulus of syntactic foams.

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Mechanical Properties Of Cu-Based Composites with in Situ Formed Ultrafine Filaments

MRS Proceedings ◽

10.1557/proc-12-121 ◽

1981 ◽

Vol 12 ◽

Author(s):

J. Bevk ◽

W. A. Sunder ◽

G. Dublon ◽

David E. Cohen

Keyword(s):

Mechanical Properties ◽

Tensile Strength ◽

Ultimate Tensile Strength ◽

Young’S Modulus ◽

Size Dependence ◽

Young's Modulus ◽

Plastic Properties ◽

Young’S Moduli ◽

Lattice Softening

ABSTRACTElastic and plastic properties of in situ Cu-based composites with Nb, V, and Fe filaments are reviewed. The evidence is presented for a pronounced size dependence of both the ultimate tensile strength and the Young's moduli. In composites with the smallest filaments (d∼50–200Å) and filament densities as high as 1010/cm2 dislocation density reaches values of 1013 cm/cm3. The yield stress of these samples increases dramatically over the predictions based on the “rule of mixtures” and their ultimate tensile strength approaches the estimated theoretical strength of the material (∼2.7GPa). The observed decrease of Young's modulus as a function of inverse wire diameter in the as-drawn composites is attributed to lattice softening due to high density of extended lattice defects. Upon annealing, Young's modulus increases by as much as 100% and exceeds the maximum values calculated from bulk elastic constants. Possible mechanisms leading to modulus enhancement and to related changes in magnetic and superconducting behavior of in situ composites are discussed.

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