Effects of non-steroidal antiinflammatory drugs and dexamethasone on the activity and expression of matrix metalloproteinase-1, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by bovine articular chondrocytes

AbstractObjective To determine the in-vitro effects of several non-steroidal antiinflammatory drugs and the glucocorticoid dexamethasone on the IL-1 altered expression and activity of MMP-1, MMP-3 and TIMP-1 by bovine articular chondrocytes.Design Bovine chondrocytes were cultured in alginate gel beads. Cells were treated with IL-1α in the presence of vehicle or drugs at various concentrations. After 48h mRNA expression of MMP-1, MMP-3, and of the tissue inhibitor of metalloproteinases (TIMP-1) was analysed by RT-PCR-ELISA. The protein synthesis of TIMP-1 and MMP-3 was determined by immunoprecipitation. The activity of enzymes and inhibitors was measured by functional assays.Results IL-1 increased the expression and activity of MMPs. In contrast, TIMP activity remained unchanged although TIMP-1 expression was down-regulated. All tested NSAIDs and dexamethasone inhibited collagenase activity induced by IL-1. Transcript levels of MMP-1, however, were only reduced by indomethacin, meloxicam, naproxen and dexamethasone. Proteoglycanase activity was only reduced by indomethacin, meloxicam and dexamethasone. These effects were pre-translational as confirmed by immunoprecipitation. The IL-1 decreased expression of TIMP-1 was further reduced by dexamethasone, which resulted in a significant loss of TIMP activity. No effects on TIMP activity or TIMP-1 biosynthesis were observed after treatment of chondrocytes with NSAIDs.Conclusion Our studies clearly demonstrate that marked differences exist between individual NSAIDs with respect to their ability to modulate the imbalance between proteases and inhibitors during OA and RA, suggesting that the respective modes of action are independent of the inhibition of cyclooxygenases. Due to their co-regulation of MMPs and TIMP(s) glucocorticoids should be carefully studied for their overall effect on ECM proteolysis

Novel Quaternary Dilute Magnetic Semiconductor (Ga,Mn)(Bi,As): Magnetic and Magneto-Transport Investigations

Magnetic and magneto-transport properties of thin layers of the (Ga,Mn)(Bi,As) quaternary dilute magnetic semiconductor grown by the low-temperature molecular-beam epitaxy technique on GaAs substrates have been investigated. Ferromagnetic Curie temperature and magneto-crystalline anisotropy of the layers have been examined by using magneto-optical Kerr effect magnetometry and low-temperature magneto-transport measurements. Postgrowth annealing treatment has been shown to enhance the hole concentration and Curie temperature in the layers. Significant increase in the magnitude of magnetotransport effects caused by incorporation of a small amount of Bi into the (Ga,Mn)As layers revealed in the planar Hall effect (PHE) measurements, is interpreted as a result of enhanced spin-orbit coupling in the (Ga,Mn)(Bi,As) layers. Two-state behaviour of the planar Hall resistance at zero magnetic field provides its usefulness for applications in nonvolatile memory devices.Comment: 10 pages, 3 figures, to be published in the Proceedings of ICSM-2016 conferenc

Thickness dependence of magnetic properties of (Ga,Mn)As

We report on a monotonic reduction of Curie temperature in dilute ferromagnetic semiconductor (Ga,Mn)As upon a well controlled chemical-etching/oxidizing thinning from 15 nm down to complete removal of the ferro- magnetic response. The effect already starts at the very beginning of the thinning process and is accompanied by the spin reorientation transition of the in-plane uniaxial anisotropy. We postulate that a negative gradient along the growth direction of self-compensating defects (Mn interstitial) and the presence of surface donor traps gives quantitative account on these effects within the p-d mean field Zener model with adequate mod- ifications to take a nonuniform distribution of holes and Mn cations into account. The described here effects are of practical importance for employing thin and ultrathin layers of (Ga,Mn)As or relative compounds in concept spintronics devices, like resonant tunneling devices in particular.Comment: 4 pages, 4 figures and supplementary information 2 pages, 1 figur

Cubic anisotropy in high homogeneity thin (Ga,Mn)As layers

Historically, comprehensive studies of dilute ferromagnetic semiconductors, e.g., $p$-type (Cd,Mn)Te and (Ga,Mn)As, paved the way for a quantitative theoretical description of effects associated with spin-orbit interactions in solids, such as crystalline magnetic anisotropy. In particular, the theory was successful in explaining {\em uniaxial} magnetic anisotropies associated with biaxial strain and non-random formation of magnetic dimers in epitaxial (Ga,Mn)As layers. However, the situation appears much less settled in the case of the {\em cubic} term: the theory predicts switchings of the easy axis between in-plane $\langle 100\rangle$ and $\langle 110\rangle$ directions as a function of the hole concentration, whereas only the $\langle 100\rangle$ orientation has been found experimentally. Here, we report on the observation of such switchings by magnetization and ferromagnetic resonance studies on a series of high-crystalline quality (Ga,Mn)As films. We describe our findings by the mean-field $p$-$d$ Zener model augmented with three new ingredients. The first one is a scattering broadening of the hole density of states, which reduces significantly the amplitude of the alternating carrier-induced contribution. This opens the way for the two other ingredients, namely the so-far disregarded single-ion magnetic anisotropy and disorder-driven non-uniformities of the carrier density, both favoring the $\langle 100\rangle$ direction of the apparent easy axis. However, according to our results, when the disorder gets reduced a switching to the $\langle 110\rangle$ orientation is possible in a certain temperature and hole concentration range.Comment: 12 pages, 9 figure

Graphene on Pt(111): Growth and substrate interaction

In situ low-energy electron microscopy (LEEM) of graphene growth combined with measurements of the graphene structure and electronic band structure has been used to study graphene on Pt (111). Growth by carbon segregation produces macroscopic monolayer graphene domains extending continuously across Pt (111) substrate steps and bounded by strongly faceted edges. LEEM during cooling from the growth temperature shows the propagation of wrinkles in the graphene sheet, driven by thermal stress. The lattice mismatch between graphene and Pt (111) is accommodated by moiré structures with a large number of different rotational variants, without a clear preference for a particular interface geometry. Fast and slow growing graphene domains exhibit moiré structures with small [e.g., (3X3) G, (6X6) R2G, and (2X2) R4] and large unit cells [e.g., (44 x44) R15G, (52x52) R14G, and (8x8) G], respectively. A weak substrate coupling, suggested by the growth and structural properties of monolayer graphene on Pt (111), is confirmed by maps of the band structure, which is close to that of isolated graphene aside from minimal hole doping due to charge transfer from the metal. Finally, the decoupled graphene monolayer on Pt (111) appears impenetrable to carbon diffusion, which self-limits the graphene growth at monolayer thickness. Thicker graphene domains, which can form at boundaries between monolayer domains, have been used to characterize the properties of few-layer graphene on Pt (111)

Graphene on Pt(111): Growth and substrate interaction

In situ low-energy electron microscopy (LEEM) of graphene growth combined with measurements of the graphene structure and electronic band structure has been used to study graphene on Pt (111). Growth by carbon segregation produces macroscopic monolayer graphene domains extending continuously across Pt (111) substrate steps and bounded by strongly faceted edges. LEEM during cooling from the growth temperature shows the propagation of wrinkles in the graphene sheet, driven by thermal stress. The lattice mismatch between graphene and Pt (111) is accommodated by moiré structures with a large number of different rotational variants, without a clear preference for a particular interface geometry. Fast and slow growing graphene domains exhibit moiré structures with small [e.g., (3X3) G, (6X6) R2G, and (2X2) R4] and large unit cells [e.g., (44 x44) R15G, (52x52) R14G, and (8x8) G], respectively. A weak substrate coupling, suggested by the growth and structural properties of monolayer graphene on Pt (111), is confirmed by maps of the band structure, which is close to that of isolated graphene aside from minimal hole doping due to charge transfer from the metal. Finally, the decoupled graphene monolayer on Pt (111) appears impenetrable to carbon diffusion, which self-limits the graphene growth at monolayer thickness. Thicker graphene domains, which can form at boundaries between monolayer domains, have been used to characterize the properties of few-layer graphene on Pt (111)

On the gradient of the yield plateau in structural carbon steels

New design methodologies are being developed to allow stocky steel members to attain and exceed the full plastic condition. For theoretical validation, such methods require a characterisation of the uniaxial stress-strain behaviour of structural steel beyond an idealised elastic-plastic representation. However, the strain hardening properties of carbon steels are not currently guaranteed by the standards or by any steel manufacturer. Assumptions must thus be made on what values of these properties are appropriate, often based on limited information in the form of individual stress-strain curves. There is very little consistency in the choices made. This paper first illustrates, using an example elastic-plastic finite element calculation, that a stocky tubular structure can attain the full plastic condition at slendernesses comparable with those defined in current standards and supported by experiment when using only a very modest level of strain hardening, initiated at first yield. It is then hypothesised that the yield plateau in the stress-strain curve for structural carbon steels, classically treated as flat and with zero tangent modulus, actually has a small but statistically significant positive finite gradient. Finally, a robust set of linear regression analyses of yield plateau gradients extracted from 225 tensile tests appears to support this hypothesis, finding that the plateau gradient is of the order of 0.3% of the initial elastic modulus, consistent with what the finite element example suggests is sufficient to reproduce the full plastic condition at experimentally-supported slendernesses