772 research outputs found

    Entangled single-wire NiTi material: a porous metal with tunable superelastic and shape memory properties

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    NiTi porous materials with unprecedented superelasticity and shape memory were manufactured by self-entangling, compacting and heat treating NiTi wires. The versatile processing route used here allows to produce entanglements of either superelastic or ferroelastic wires with tunable mesostructures. Three dimensional (3D) X-ray microtomography shows that the entanglement mesostructure is homogeneous and isotropic. The thermomechanical compressive behavior of the entanglements was studied using optical measurements of the local strain field. At all relative densities investigated here (∌\sim 25 - 40%\%), entanglements with superelastic wires exhibit remarkable macroscale superelasticity, even after compressions up to 25%\%, large damping capacity, discrete memory effect and weak strain-rate and temperature dependencies. Entanglements with ferroelastic wires resemble standard elastoplastic fibrous systems with pronounced residual strain after unloading. However, a full recovery is obtained by heating the samples, demonstrating a large shape memory effect at least up to 16% strain.Comment: 31 pages, 10 figures, submitted to Acta Materiali

    Fabrication of Net-Shape Functionally Graded Composites by Electrophoretic Deposition and Sintering: Modeling and Experimentation

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    It is shown that electrophoretic deposition (EPD) sintering is a technological sequence that is capable of producing net-shape bulk functionally graded materials (FGM). By controlling the shape of the deposition electrode, components of complex shapes can be obtained. To enable sintering net-shape capabilities, a novel optimization algorithm and procedure for the fabrication of net-shape functionally graded composites by EPD and sintering has been developed. The initial shape of the green specimen produced by EPD is designed in such a way that the required final shape is achieved after sintering-imposed distortions. The optimization is based on a special innovative iteration procedure that is derived from the solution of the inverse sintering problem: the sintering process is modeled in the “backward movie” regime using the continuum theory of sintering incorporated into a finite-element code. The experiments verifying the modeling approach include the synthesis by EPD of Al2O3/ZrO2 3-D (FGM) structures. In order to consolidate green parts shaped by EPD, post-EPD sintering is used. The fabricated deposits are characterized by optical and scanning electron microscopy. The experimentally observed shape change of the FGM specimen obtained by EPD and sintering is compared with theoretical predictions

    Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.

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    High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA(A) receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA(A) receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA(A) receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA(A)-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA(A) receptors, has been related to psychiatric disorders including schizophrenia and depression

    Profile of French community-dwelling older adults supplemented with vitamin D: findings and lessons

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    INTRODUCTION: The vast majority of older French adults exhibit some degree of hypovitaminosis D. The objective of this cross-sectional study was to determine the rate and the reasons for vitamin D prescription among older French adult community dwellers. METHODS: Vitamin D supplementation was systematically assessed among 1876 French community dwellers aged ≄ 65 years. Theoretical indications for vitamin D supplementation were collected, ie, the causes of hypovitaminosis D (older age, male gender, kidney failure, undernutrition, polymorbidity) or its clinical complications (vertebral or non-vertebral fractures, gait disturbances, history of falls, muscle weakness, and cognitive impairment). RESULTS: In total, 13.8% of the subjects (n=258) had vitamin D supplementation. They were more often malnourished (P=0.002), exhibited polymorbidity (P<0.001) and muscle weakness (P<0.001), and had a history of vertebral fractures (P<0.001), non-vertebral fractures (P<0.001), and accidental falls (P<0.001). Vitamin D supplementation was explained by the number of complications of hypovitaminosis D (odds ratio [OR]=1.61, P<0.001) including vertebral fractures (adjusted OR=1.49, P=0.007), non-vertebral fractures (adjusted OR=1.74, P=0.026), accidental falls (adjusted OR=1.44, P=0.015), and muscle weakness (adjusted OR=3.96, P<0.001), but not by the number of causes of hypovitaminosis D (P=0.464). CONCLUSION: Even if vitamin D supplementation is selected well for appropriate patients, the rate of supplementation remains insufficient in France, and probably comes too late, ie, at the stage of complications of hypovitaminosis D. These findings should encourage physicians to supplement vitamin D more often and sooner in their elderly patients

    Fracture incidence after 3 years of aromatase inhibitor therapy

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    BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women

    Enteroendocrine K-cells exert complementary effects to control bone quality and mass in mice

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    International audienceThe involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K-cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K-cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecula number and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K-cells, suggesting that other K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity

    The Role of Protein Kinase A Regulation of the E6 PDZ-Binding Domain during the Differentiation-Dependent Life Cycle of Human Papillomavirus Type 18

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    Human papillomavirus (HPV) E6 proteins of high-risk alpha types target a select group of PSD95/DLG1/ZO1 (PDZ) domain-containing proteins by using a C-terminal PDZ-binding motif (PBM), an interaction that can be negatively regulated by phosphorylation of the E6 PBM by protein kinase A (PKA). Here, we have mutated the canonical PKA recognition motif that partially overlaps with the E6 PBM in the HPV18 genome (E6153PKA) and compared the effect of this mutation on the HPVl8 life cycle in primary keratinocytes with the wild-type genome and with a second mutant genome that lacks the E6 PBM (E6ΔPDZ). Loss of PKA recognition of E6 was associated with increased growth of the genome-containing cells relative to cells carrying the wild-type genome, and upon stratification, a more hyperplastic phenotype, with an increase in the number of S-phase competent cells in the upper suprabasal layers, while the opposite was seen with the E6ΔPDZ genome. Moreover, the growth of wild-type genome-containing cells was sensitive to changes in PKA activity, and these changes were associated with increased phosphorylation of the E6 PBM. In marked contrast to E6ΔPDZ genomes, the E6153PKA mutation exhibited no deleterious effects on viral genome amplification or expression of late proteins. Our data suggest that the E6 PBM function is differentially regulated by phosphorylation in the HPV18 life cycle. We speculate that perturbation of protein kinase signaling pathways could lead to changes in E6 PBM function, which in turn could have a bearing on tumor promotion and progression
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