The design of the next generation of β-stabilized γ-TiAl based alloys as structural materials for high-temperature applications in aircraft engines requires the precise knowledge of the mobility of ...defects in the ordered βo phase. To reach this goal a Mo-rich prototype alloy has been specifically produced and investigated. The mobility of defects, between 600K and 1635K, has been studied by mechanical spectroscopy. The internal friction spectra show a relaxation peak P1 (at 1130K for 1Hz) superimposed to a high-temperature background. We demonstrate that the relaxation peak is taking place inside the βo phase and measure an activation energy of EP1 = 3.55 ± 0.05eV. An atomistic model is additionally proposed to explain this relaxation peak, which is attributed to a Zener-like mechanism of stress-induced Mo-Mo dipoles reorientation by exchange with a vacancy, and consequently the measured activation energy corresponds to the one for Mo diffusion in the βo phase.
The directional spectral emissivity of a Ti–48Al–2Nb–2Cr alloy (in at.%), 4822 alloy, and a Ti-43.5Al–4Nb–1Mo-0.1B alloy (in at.%),TNM alloy, used in the aeronautical industry, are measured between ...150 and 850 °C. The differences in the emissivity values between both alloys at the lowest temperatures, indicates that the βo phase, only present in TNM, exhibit higher emissivity values. By numerical integration of the measured data, the total directional and hemispherical emissivity have been calculated. At 850 °C the total hemispherical emissivity in vacuum are nearly identical with 0.274 ± 0.006 for the 4822 alloy and 0.273 ± 0.007 for the TNM alloy. The lower emissivity change with temperature measured in TNM alloys is related with the deconvolution of βo phase by diffusion processes. Afterwards, near-normal spectral emissivity measurements are performed in both alloys during isothermal oxidation treatments at 750 °C and 850 °C for 120 h. The emissivity data reveal that the TNM alloy exhibits higher oxidation resistance especially at 750 °C. In parallel, microstructural characterization has been performed before the measurements, after the directional emissivity measurements prior to oxidation and after isothermal oxidations. The formed oxide scale is composed of four layers that coincide with those reported in the literature: an outer layer of TiO2 contiguous with a layer of Al2O3, followed by a TiO2/Al2O3 mixed layer and finally a thin layer of Nb-rich nitride. This mixed layer governs the interferential part of the alloys’ emissivity spectra, which, in combination with the background, determines the overall radiative behavior of the alloys under service conditions.
In the present work we have studied a high temperature Ru-50Nb (at.%) shape memory alloy using a mechanical spectrometer able to work in the temperature range from 473 to 1723K. We have investigated ...two internal friction peaks, as well as the dynamic modulus variation, linked to the martensitic transformations in the range from 573K to 1473K. In addition, we have evidenced another internal friction peak PLT at lower temperature than the transformation peaks, which apparently exhibits the behaviour of a thermally activated relaxation peak. However, we show that this peak is not a relaxation one because it exhibits a strongly time-dependent behaviour. We have carefully analysed this peak and discussed its microscopic origin, concluding that it is related to the interaction of some structural defects with martensite interfaces.
Cardiovascular risk increases in women after menopause. Unfavorable lipid‐lipoprotein changes due to a lack of estrogens may have an important role in this context. Estrogen actions are mainly ...mediated by their binding to two estrogen receptors (ERs) whose signaling may be conditioned by different factors. Calcium, vitamin D, and genistein, among others, cause a beneficial effect on serum lipid profile by its modulation. Some genetic factors can also determine this signal. We determined the possible additive effect of genistein on calcium and vitamin D supplementation regarding serum lipid profile changes and whether ER polymorphisms may mediate in this effect.
We performed a prospective, double blind study in which women were randomized in two groups: one group received calcium and vitamin D and the other group received calcium, vitamin D and genistein. Subsequently, we studied rs9340799, rs928554, and rs4986938 ER polymorphisms in both groups.
Our results showed that being a carrier of the variant allele G of rs928554 polymorphism was associated with a greater decrease in triglyceride levels and that the homozygous AA genotype of rs9340799 polymorphism was associated with a greater decrease in total cholesterol, low‐density lipoprotein cholesterol, and triglyceride levels after calcium, vitamin D, and genistein supplementation.
This is the first report showing an association between polymorphisms in ER genes and an improvement of the serum lipid profile after taking calcium, vitamin D, and genistein supplementation in postmenopausal women. It reinforces the hypothesis that genetic factors are crucial in ER signalling.
Mesenchymal stem cells (MSC) secrete neuroprotective molecules that may be useful as an alternative to cell transplantation itself. Our purpose was to develop different pharmaceutical compositions ...based on conditioned medium (CM) of adipose MSC (aMSC) stimulated by and/or combined with nicotinamide (NIC), vasoactive intestinal peptide (VIP), or both factors; and to evaluate in vitro their proliferative and neuroprotective potential. Nine pharmaceutical compositions were developed from 3 experimental approaches: (1) unstimulated aMSC-CM collected and combined with NIC, VIP, or both factors (NIC+VIP), referred to as the aMSC-CM combined composition; (2) aMSC-CM collected just after stimulation with the mentioned factors and containing them, referred to as the aMSC-CM stimulated-combined composition; and (3) aMSC-CM previously stimulated with the factors, referred to as the aMSC stimulated composition. The potential of the pharmaceutical compositions to increase cell proliferation under oxidative stress and neuroprotection were evaluated in vitro by using a subacute oxidative stress model of retinal pigment epithelium cells (line ARPE-19) and spontaneous degenerative neuroretina model. Results showed that oxidatively stressed ARPE-19 cells exposed to aMSC-CM stimulated and stimulated-combined with NIC or NIC+VIP tended to have better recovery from the oxidative stress status. Neuroretinal explants cultured with aMSC-CM stimulated-combined with NIC+VIP had better preservation of the neuroretinal morphology, mainly photoreceptors, and a lower degree of glial cell activation. In conclusion, aMSC-CM stimulated-combined with NIC+VIP contributed to improving the proliferative and neuroprotective properties of the aMSC secretome. Further studies are necessary to evaluate higher concentrations of the drugs and to characterize specifically the aMSC-secreted factors related to neuroprotection. However, this study supports the possibility of improving the potential of new effective pharmaceutical compositions based on the secretome of MSC plus exogenous factors or drugs without the need to inject cells into the eye, which can be very useful in retinal pathologies.
Accumulation of senescent cells has been associated with pro-inflammatory effects with deleterious consequences in different human diseases. The purpose of this study was to analyze cell senescence ...in human synovial tissues (ST), and its impact on the pro-inflammatory function of synovial fibroblasts (SF).
The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal ST from variably aged donors. The proportion of p16(+) senescent cells in normal ST from older donors was higher than from younger ones. Although older RA and OA ST showed proportions of senescent cells similar to older normal ST, senescence was increased in younger RA ST compared to age-matched normal ST. The percentage of senescent SA-β-gal(+) SF after 14 days in culture positively correlated with donor's age. Initial exposure to H
O
or TNFα enhanced SF senescence and increased mRNA expression of
,
,
and
and proteins secretion. Senescent SF show a heightened
,
and
mRNA and IL-6 and IL-8 protein expression response upon further challenge with TNFα. Treatment of senescent SF with the senolytic drug fenofibrate normalized
,
and
mRNA expression.
Accumulation of senescent cells in ST increases in normal aging and prematurely in RA patients. Senescence of cultured SF is accelerated upon exposure to TNFα or oxidative stress and may contribute to the pathogenesis of synovitis by increasing the production of pro-inflammatory mediators.
Intermetallic γ-TiAl based alloys have found applications in the low-pressure turbine of aircraft engines as well as in the turbocharger unit of automotive engines. However, these light-weight alloys ...must still be improved, through micro-alloying and tailoring the microstructure, to increase their creep resistance and consequently their maximum working temperature. In this work, a fully nano-lamellar advanced γ-TiAl based alloy doped with small amounts of C and Si is investigated in order to gain a deeper understanding of the atomic mobility mechanisms taking place at high temperature, thus controlling the creep properties. The study was approached through internal friction measurements up to 1223 K. We demonstrate that C has a notable influence on Ti diffusion in α2 phase, leading to an increase of the activation energy for Ti diffusion, which is assessed at ΔETi(α2)=0.32 eV per at% C. An atomic model for the relaxation process is proposed capable to explain this phenomenon. An additional internal friction peak, which, up to now, remained hidden by the high temperature background, was observed in this nano-lamellar TiAl alloy and analyzed through a careful de-convolution of the internal friction spectra. This new relaxation process, with activation energy of 3.70 eV, is attributed to the short distance diffusion of Al atoms in the γ-TiAl lattice. A novel concept of stress-induced cell-lattice reorientation is proposed to explain this relaxation. Finally, a new experimental method to analyze the high temperature internal friction background, which is closely related to the creep behavior, was developed to study the fully nano-lamellar microstructure, whose high temperature background exhibits the highest activation energy ever measured in a γ-TiAl based alloy.
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Increased glycolysis and HIF-1α activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O
environments, elevated rates of glycolysis support critical ...cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1α to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1α was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1α target genes in hypoxia demonstrated the presence of functional HIF-1α in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a HIF-1α target even in normoxia. HIF-1α silencing induced apoptotic cell death in cultured SF and, similarly, treatment with glycolytic, but not with OXPHOS inhibitors, induced SF death. Finally, in vivo HIF-1α targeting by siRNA showed a significant reduction in the viability of human SF engrafted into a murine air pouch. Our results demonstrate that SF are highly dependent on glycolytic metabolism and that HIF-1α plays a regulatory role in glycolysis even under aerobic conditions. Local targeting of HIF-1α provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases.
•SNP in oxidative stress-related genes are crucial in osteoporotic bone fracture.•rs4077561 TXNRD1 SNP was the principal genetic risk factor associated with fracture.•Genetic factors are crucial in ...the etiopathogenesis of osteoporosis complications.
The most widely accepted etiopathogenesis hypothesis of the origin of osteoporosis and its complications is that they are a consequence of bone aging and other environmental factors, together with a genetic predisposition. Evidence suggests that oxidative stress is crucial in bone pathologies associated with aging. The aim of this study was to determine whether genetic variants in oxidative stress-related genes modified the risk of osteoporotic fracture. We analysed 221 patients and 354 controls from the HORTEGA sample after 12–14 years of follow up. We studied the genotypic and allelic distribution of 53 SNPs in 24 genes involved in oxidative stress. The results showed that being a carrier of the variant allele of the SNP rs4077561 within TXNRD1 was the principal genetic risk factor associated with osteoporotic fracture and that variant allele of the rs1805754 M6PR, rs4964779 TXNRD1, rs406113 GPX6, rs2281082 TXN2 and rs974334 GPX6 polymorphisms are important genetic risk factors for fracture. This study provides information on the genetic factors associated with oxidative stress which are involved in the risk of osteoporotic fracture and reinforces the hypothesis that genetic factors are crucial in the etiopathogenesis of osteoporosis and its complications.
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