102 research outputs found

    \u3cem\u3eIn situ\u3c/em\u3e pressure study of Rb\u3csub\u3e4\u3c/sub\u3eC\u3csub\u3e60\u3c/sub\u3e insulator to metal transition by Compton scattering

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    Compton scattering has been shown to be a powerful tool for studying the ground state electronic density in real materials. Using synchrotron radiation, we have studied pressure effects on Rb4C60 by measuring the Compton profiles below and above the insulator to metal transition at 0.8 GPa. The experimental results are compared with the corresponding calculated results, obtained from new ab initio energy band structure calculations. These results allow us to quantitatively evaluate contributions to the Compton profiles resulting from the contraction of the unit cell as well as from the contraction of the C60 molecule itself. In this paper, we point out an unexpected contraction of the volume of the C60 molecule, leading to a major effect on the electronic density of the Rb4C60 compound

    Lung Fibrosis after Chemotherapy Containing Docetaxel in a Patient Treated for Breast Cancer

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    Docetaxel has proven effective in many solid tumors, including breast cancer. Hypersensitivity reactions are the most common toxicity associated with docetaxel. However, acute interstitial pneumonia is rarely reported in the literature. We report the case of a woman born in 1969, treated for invasive ductal carcinoma of the left breast and who presented 6 years later with an invasive ductal carcinoma locally advanced in the right breast. Neo-adjuvant chemotherapy based on docetaxel was indicated. Fifteen days after the third course, she had a stage IV dyspnea with a dry cough. Chest radiography showed a bilateral diffuse interstitial infiltrate appearance labeled as an acute interstitial lung disease secondary to docetaxel. The outcome was good after a high dose of corticosteroids. Clinicians should be aware of the risk of interstitial lung disease with docetaxel and introduce a special monitoring of lung function

    Hybrid approach for energy aware management of multi-cloud architecture integrating user machines

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    International audienceThe arrival and development of remotely accessible services via the cloud has transfigured computer technology. However, its impact on personal computing remains limited to cloud-based applications. Meanwhile, acceptance and usage of telephony and smartphones have exploded. Their sparse administration needs and general user friendliness allows all people, regardless of technology literacy, to access, install and use a large variety of applications.We propose in this paper a model and a platform to offer personal computing a simple and transparent usage similar to modern telephony. In this model, user machines are integrated within the classical cloud model, consequently expanding available resources and management targets. In particular, we defined and implemented a modular architecture including resource managers at different levels that take into account energy and QoS concerns. We also propose simulation tools to design and size the underlying infrastructure to cope with the explosion of usage. Functionalities of the resulting platform are validated and demonstrated through various utilization scenarios. The internal scheduler managing resource usage is experimentally evaluated and compared with classical method-ologies, showing a significant reduction of energy consumption with almost no QoS degradation

    Evidence for distinct polymer chain orientations in KC60 and RbC60

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    The KC60 and RbC60 polymer phases exhibit contrasting electronic properties while powder diffraction studies have revealed no definite structural difference. We have performed single crystal X-ray diffraction and diffuse scattering studies of these compounds. It is found that KC60 and RbC60 possess different chain orientations about their axes, which are described by distinct space groups Pmnn and I2/m, respectively. Such a structural difference will be of great importance to a complete understanding of the physical properties.Comment: To be published in Phys. Rev. Let

    Homocysteine metabolism pathway is involved in the control of glucose homeostasis: a cystathionine beta synthase deficiency study in mouse

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    Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/-) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/- mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/- mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis

    Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2)

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    Aims/hypothesis Rapamycin (sirolimus) is one of the primary immunosuppressants for islet transplantation. Yet there is evidence that the long-term treatment of islet-transplant patients with rapamycin may be responsible for subsequent loss of islet graft function and viability. Therefore, the primary objective of this study was to elucidate the molecular mechanism of rapamycin toxicity in beta cells. Methods Experiments were performed on isolated rat and human islets of Langerhans and MIN6 cells. The effects of rapamycin and the roles of mammalian target of rapamycin complex 2 (mTORC2)/protein kinase B (PKB) on beta cell signalling, function and viability were investigated using cell viability assays, insulin ELISA assays, kinase assays, western blotting, pharmacological inhibitors, small interfering (si)RNA and through the overproduction of a constitutively active mutant of PKB

    Genomic copy number variation in Mus musculus.

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    BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously. RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR). CONCLUSION: The analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies

    Glucose Amplifies Fatty Acid-Induced Endoplasmic Reticulum Stress in Pancreatic Ξ²-Cells via Activation of mTORC1

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    BACKGROUND: Palmitate is a potent inducer of endoplasmic reticulum (ER) stress in beta-cells. In type 2 diabetes, glucose amplifies fatty-acid toxicity for pancreatic beta-cells, leading to beta-cell dysfunction and death. Why glucose exacerbates beta-cell lipotoxicity is largely unknown. Glucose stimulates mTORC1, an important nutrient sensor involved in the regulation of cellular stress. Our study tested the hypothesis that glucose augments lipotoxicity by stimulating mTORC1 leading to increased beta-cell ER stress. PRINCIPAL FINDINGS: We found that glucose amplifies palmitate-induced ER stress by increasing IRE1alpha protein levels and activating the JNK pathway, leading to increased beta-cell apoptosis. Moreover, glucose increased mTORC1 activity and its inhibition by rapamycin decreased beta-cell apoptosis under conditions of glucolipotoxicity. Inhibition of mTORC1 by rapamycin did not affect proinsulin and total protein synthesis in beta-cells incubated at high glucose with palmitate. However, it decreased IRE1alpha expression and signaling and inhibited JNK pathway activation. In TSC2-deficient mouse embryonic fibroblasts, in which mTORC1 is constitutively active, mTORC1 regulated the stimulation of JNK by ER stressors, but not in response to anisomycin, which activates JNK independent of ER stress. Finally, we found that JNK inhibition decreased beta-cell apoptosis under conditions of glucolipotoxicity. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings suggest that mTORC1 mediates glucose amplification of lipotoxicity, acting through activation of ER stress and JNK. Thus, mTORC1 is an important transducer of ER stress in beta-cell glucolipotoxicity. Moreover, in stressed beta-cells mTORC1 inhibition decreases IRE1alpha protein expression and JNK activity without affecting ER protein load, suggesting that mTORC1 regulates the beta-cell stress response to glucose and fatty acids by modulating the synthesis and activity of specific proteins involved in the execution of the ER stress response. This novel paradigm may have important implications for understanding beta-cell failure in type 2 diabetes
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