Évaluation de polymorphismes de p22phox, RAGE et ALOX12 dans la survenue de la néphropathie diabétique chez le type 1 (projet NEPHRODIANOX)

Le stress oxydant est un des mécanismes clefs dans la physiopathologie de la néphropathie diabétique chez le patient type 1. Nous avons évalué l association de polymorphismes de trois gènes impliqués dans cette voie : C242T de CYBA (p22phox), -374T/A et -429T/C de RAGE, et Arg261Gln d ALOX12, dans le délai de survenue de la néphropathie microalbuminurique chez le patient diabétique de type 1. 162 patients type 1, ancienneté moyenne du diabète de 32,9 +/- 9 ans, inclus au CHU de Grenoble. 53 patients présentaient une microalbuminurie (> 30 mg/L) et 109 indemnes de néphropathie. Nous avons determiné pour chaque patient son statut vis-à-vis de chacun des polymorphysmes étudiés, et évalué leurs associations à la survenue de la microalbuminurie dans un modèle de cox. Le modèle de cox en analyse multi-variée retrouve quatre facteurs associés au délai de survenue de la néphroapthie diabétique : RAGE 374AA (HR 4.19 [1.84-9.58] (p=0.001)), p22phox TT+TC (HR 2.1 [1.16-3.8], p= 0.015), mais égalment le sexe masculin (HR 1.92 [1.07-3.43], p=0.028) et le diagnostique du diabète à l âge pédiatrique (HR 1.85 [1.03-3.32], p=0.039). Nous retrouvons également une association avec le délai de survenue de l IRCT (p= 0.028 pour p22phox TC+TT, et p=0.033 pour RAGE 374AA). Le polymorphisme C242T de p22phox semble indépendant de la rétinopathie. Conclusion : les polymorphismes C242T de p22phox et -374T/A de RAGE sont associés à une survenue plus précoce de la microalbuminurie dans une population de diabétiques de type 1 française. L indépendance de la rétinopathie ainsi que l association avec la survenue de l IRCT nous fournissent des arguments supplémentaires leur implication.Background: Oxidative stress is a key component of type 1 diabetic nephropathy. Therefore, we investigated the association between polymorphisms of three genes implicated in this pathway: C242T of CYBA (p22phox), -374T/A and -429T/C of RAGE, as Arg261Gln of ALOX 12, in the delay of microalbuminuria onset in type 1 diabetic patients. Methods: 162 diabetic type 1 patients with 32.9 +/- 9 years of diabetes duration were included at the Grenoble University Hospital. 53 presented a history of persistent microalbuminuria (> 30 mg/l) and 109 did not. Delay between microalbuminuria and diabetes diagnosis, as end stage renal disease (ESRD) onset and bio-clinical data, were recorded. Polymorphism status was determined and its association to microalbumuria was assessed with a Cox regression model. Results: All polymorphisms respect the Hardy Weinberg equilibrium. At univariate level, C242T dominant model (13.6% TT, 45.7% TC, 41.7% CC) and -374T/A (5.6% AA, 35.2% TA, 59% TT) were significantly correlated with microalbuminuria (p=0.038, 0.0021 respectively). The Cox regression model validated four significant variables: RAGE 374AA (HR 4.19 [1.84-9.58] (p=0.001)), p22phox TT+TC (HR 2.1 [1.16-3.8], p= 0.015), associated with male sex (HR 1.92 [1.07-3.43], p=0.028) and diabetes diagnosis at pediatric age (HR 1.85 [1.03-3.32], p=0.039). The same association was found with ESRD (p= 0.028 for p22phox TC+TT, and p=0.033 for RAGE 374AA). The C242T polymorphism was independent of retinopathy onset (66.7% of CC patients versus 63.6% of CT+TT p=0.6 for superiority and p=0.043 for non inferiority). Finally we suspected an increasing risk with polymorphism associations but it did not reach significant level. Conclusions: p22phox C242T, and RAGE-374T/A correlate with microalbuminuria onset in a type 1 diabetic French population. The same correlation with ESRD onset provides argument for the involvement of a genetic predisposition involving renal oxidative stress for diabetic nephropathy independently of retinopathy for C242T.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Gaussian Boson Sampling with Pseudo-Photon-Number Resolving Detectors and Quantum Computational Advantage

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ~ 600 years using exact methods, whereas our quantum computer, Jiuzhang 3.0, takes only 1.27 us to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier ~ 3.1*10^10 years.Comment: submitted on 10 Apri

Statistical particle stress in aeolian sand movement-derivation and validation

The statistical particle stress (SPS) is a result of group particle movement, which is not referred directly from E–L (Euler–Lagrange) calculations. This paper derives SPS in Eulerian regime and proves that in aeolian sand movement, as the height increases the gas stress also increases while the SPS decreases; however, the sum of gas stress and SPS keeps to be a constant value, which equals to the gas stress in particle absent region. This paper also suggests that SPS predominates in the momentum transportation of particle phase

High flux polyamide thin film composite forward osmosis membranes prepared from porous substrates made of polysulfone and polyethersulfone blends

High water flux polyamide thin film composite (TFC) forward osmosis (FO) membranes with porous supporting substrate layers made from polysulfone (PSf) and polyethersulfone (PES) blends of varied PSf/PES ratio were prepared. The impact of PSf/PES ratio on the porous structure of the supporting substrates and resulting properties of TFC-FO membranes formed were investigated. There were three distinguished sections observed in the cross-sections of the substrates, a top dense skin section, a central porous section, and a bottom open section according to SEM images. With the joint favoring effects from maximum open bottom section percentage in the cross-section and maximum surface roughness, membrane samples made from substrates with a PSf/PES ratio of 2/3 exhibit a highest water flux of 27.6 L/m(2) h for 2 M NaCl draw solution from a de-ionized water feed solution. And their water flux reached 12.7 L/m(2) h under PRO mode and 10.6 L/m(2) h under FO mode from an ocean seawater feed solution containing 3.5 wt.% of NaCl. This high flux is related to the existence of heavily populated cone shaped protrusions observed on the surfaces of formed TFC-FO membranes, resulting from amplification in initial surface roughness of the porous substrate during the active layer forming interfacial co-polymerization process. (C) 2014 Elsevier B.V. All rights reserved

Superior Clone Selection in a <i>Eucalyptus</i> Trial Using Forest Phenotyping Technology via UAV-Based DAP Point Clouds and Multispectral Images

The quantitative, accurate and efficient acquisition of tree phenotypes is the basis for forest “gene-phenotype-environment” studies. It also offers significant support for clarifying the genetic control mechanisms of tree traits. The application of unmanned aerial vehicle (UAV) remote sensing technology to the collection of phenotypic traits at an individual tree level quantitatively analyses tree phenology and directionally evaluates tree growth, as well as accelerating the process of forest genetics and breeding. In this study, with the help of high-resolution, high-overlap, multispectral images obtained by an UAV, combined with digital elevation models (DEMs) extracted from point clouds acquired by a backpack LiDAR, a high-throughput tree structure and spectral phenotypic traits extraction and a genetic selection were conducted in a trial of Eucalyptus clones in the State-owned Dongmen Forest Farm in the Guangxi Zhuang Autonomous Region. Firstly, we validated the accuracy of extracting the phenotypic parameters of individual tree growth based on aerial stereo photogrammetry point clouds. Secondly, on this basis, the repeatability of the tree growth traits and vegetation indices (VIs), the genetic correlation coefficients between the traits were calculated. Finally, the eucalypt clones were ranked by integrating a selection index of traits, and the superior genotypes were selected and their genetic gain predicted. The results showed a high accuracy of the tree height (H) extracted from the digital aerial photogrammetry (DAP) point cloud based on UAV images (R2 = 0.91, and RMSE = 0.56 m), and the accuracy of estimating the diameter at breast height (DBH) was R2 = 0.71, and RMSE = 0.75 cm. All the extracted traits were significantly different within the tree species and among the clones. Except for the crown width (CW), the clonal repeatability (Rc) of the traits were all above 0.9, and the individual repeatability values (Ri) were all above 0.5. The genetic correlation coefficient between the tree growth traits and VIs fluctuated from 0.3 to 0.5, while the best clones were EA14-15, EA14-09, EC184, and EC183 when the selection proportion was 10%. The purpose of this study was to construct a technical framework for phenotypic traits extraction and genetic analysis of trees based on unmanned aerial stereo photography point clouds and high-resolution multispectral images, while also exploring the application potential of this approach in the selective breeding of eucalypt clones

Development and in vitro evaluation of deacety mycoepoxydiene nanosuspension

National Basic Research Program of China (973 Program) [2009CB930300]; Major scientific and technological specialized project for Significant New Formulation of New Drugs [2009ZX09502-001]Deacety mycoepoxydiene (DM), extracted from Phomopsis sp. A123 of thalassiomycetes, is a novel and potent anti-cancer agent. Due to its physicochemical characteristics, the drug, a poorly water-soluble weak acid, shows poor solubility and dissolution characteristics. To improve the solubility and dissolution, formulation of DM as nanosuspension has been performed in this study. Nanosuspensions were developed by high-pressure homogenization (HPH) (DissoCubes (R) Technology) and transformed into dry powder by freeze-drying. The nanosuspension produced was then investigated using optical microscope, photon correlation spectroscopy (PCS), zeta potential measurement, SEM, TEM, AFM, DSC and XRD. To verify the theoretical hypothesis on the benefit of increased surface area, in vitro saturation solubility and dissolution profile were investigated. In addition, the in vitro cell cytotoxicity was examined. Results showed that a narrow size distributed nanosuspension composed of unchanged crystalline state with a mean particle size of 515 +/- 18 nm, a polydispersity index of 0.12 +/- 0.03 and a zeta potential of -23.1 +/- 3.5 mV was obtained. In the in vitro dissolution test an accelerated dissolution velocity and increased saturation solubility could be shown for the MD nanosuspension. The in vitro cytotoxicity experiments provided evidence for an enhanced efficacy of the DM nanosuspension formulation compared to free DM solution. Taken together, these results illustrate the opportunity to formulate DM in nanosuspension form as an anti-prostate cancer delivery system. (C) 2010 Published by Elsevier B.V

Carbonized Polymer Dots Enhancing Interface Stability of LiNi0.8Co0.1Mn0.1O2 Cathodes

Abstract The high energy density, low cost, and low toxicity of LiNi0.8Co0.1Mn0.1O2 (NCM811) cathodes has led to their large‐scale mass production. However, the poor interfacial stability between NCM811 and organic electrolytes impairs the long‐cycle performance of lithium ions batteries. In this study, carbonized polymer dots (CPDs) are successfully introduced onto the surface of NCM811 (NCM811@CPDs) via a simple physical mixing process. CPDs with rich surface oxygen functional groups form strong covalent bonds with transition metal (TM) ions at the NCM811 surface, distinctly restraining surface structure degradation, and transition metal ion dissolution. Furthermore, CPDs facilitate the formation of a compact and steady cathode electrolyte interface (CEI) layer during electrochemical cycling. As a result, the NCM811@1 wt% CPDs exhibit enhanced cycling performance with a capacity retention of 89.77% after 100 cycles at 0.5 C compared to 55.39% of the bare NCM811. This facile and effective surface decoration strategy provides valuable guidance for improving the stability and cycling performance of Ni‐rich cathodes