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91.
Thierry Giordano 《Planning Theory & Practice》2013,14(4):480-504
The South African government has named the transition towards a greener economy one of its priorities. Meanwhile it has developed a new multilevel integrated planning process, and announced a massive public infrastructure investment plan. The converging point of these three dynamics should be the integration of green infrastructure principles into the different plans as the foundation of the green transition. This paper uses a policy integration analytical framework to assess whether this convergence is in fact taking shape. It analyses the level of integration of green infrastructure principles into the different plans and suggests options to move the green infrastructure agenda forward. 相似文献
92.
Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold‐Hopping Approach
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Dr. Bibia Heidmann Dr. John Gatfield Dr. Catherine Roch Dr. Alexander Treiber Dr. Simone Tortoioli Dr. Christine Brotschi Dr. Jodi T. Williams Dr. Martin H. Bolli Dr. Stefan Abele Dr. Thierry Sifferlen Dr. François Jenck Dr. Christoph Boss 《ChemMedChem》2016,11(19):2132-2146
Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold‐hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time‐dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P‐glycoprotein (Pgp)‐mediated efflux. Compound 80 c [{(1S,6R)‐3‐(6,7‐difluoroquinoxalin‐2‐yl)‐3,8‐diazabicyclo[4.2.0]octan‐8‐yl}(4‐methyl‐[1,1′‐biphenyl]‐2‐yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium‐release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep‐promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant. 相似文献
93.
Wenbo Yu Véronique Gauthier‐Brunet Thierry Cabioc'h Sylvain Dubois 《Journal of the American Ceramic Society》2014,97(7):2308-2313
Ti, TiC, Al and AlN powders were mixed to synthesize Ti2Al(CxNy) (x + y < 1) solid solutions, Ti2AlCx (x < 1) and Ti2AlN‐related end‐members by hot isostatic pressing at 1400°C/80 MPa for 4 h. For the pure carbides, it is demonstrated that single‐phased samples can only be obtained when about 15% of substoichiometry on the carbon site is applied. Such a result likely implies that Ti2AlCx can only exist in a narrow range of carbon composition. Ti2AlN nitride can be synthesized with y = 1. Assuming that vacancy content varies linearly from 0 to 0.15 going from Ti2AlN to Ti2AlC0.85 in the solid solutions, element concentrations have been calculated to synthesize different solid solutions. Thus, it is demonstrated that single‐phased and fully dense Ti2Al(C0.23N0.71), Ti2Al(C0.45N0.45), and Ti2Al(C0.66N0.22) carbonitrides can be synthesized. 相似文献
94.
Jie Li Lyes Bennamoun Laurent Fraikin Thierry Salmon Dominique Toye Raphael Schreinemachers 《Drying Technology》2014,32(14):1706-1717
Convective drying of wastewater sludges and sawdust/sludge mixtures was studied. The first part of this work was an experimental study performed in a cross-flow convective dryer using 500 g of wet material extruded through a disk with circular dies of 12 mm. The results showed that the sawdust addition has a positive impact on the drying process from a mass ratio of 2/8, on a dry basis, with observed drying rates higher than the original sludge. The second part of this work consisted of developing a drying model in order to identify the internal diffusion coefficient and convective mass transfer coefficient from the experimental data. A comparison was made between fitted drying curves, well represented by the Newton's model, and the analytical solutions of the diffusion equation applied to a finite cylinder. Variations of dimensional characteristics, such as the volume and exchange surface of the sample bed, were obtained by X-ray tomography. This technique allowed us to confirm that shrinkage, which is an important phenomenon occurring during sludge and sawdust/sludge mixture drying, must be taken into account. The results showed that both the internal diffusion coefficient and convective mass transfer coefficient were affected by mixing and sawdust addition. The internal diffusion coefficient changed from 7.77 × 10?9 m2/s for the original sludge to 7.01 × 10?9 m2/s for the mixed sludge and then increased to 8.35 × 10?9 m2/s for the mixture of a mass ratio of 4/6. The convective mass transfer coefficient changed from 9.70 × 10?8 m/s for the original sludge to 8.67 × 10?8 m/s for the mixed sludge and then increased to 12.09 × 10?8 m/s for the mixture of a mass ratio of 4/6. These results confirmed that sawdust addition was beneficial to the sludge drying process as the mass transfer efficiency between the air and material increased. Reinforcing the texture of sludge by adding sawdust can increase the drying rate and decrease the drying time, and then the heat energy supply will be reduced significantly. The study also showed that neglecting shrinkage phenomenon resulted in an overestimation for the internal diffusion coefficient for the convective drying of sludges and sawdust/sludge mixtures. 相似文献
95.
Pierre-Jean Ferron Brendan Le Dar Julie Bronsard Clara Steichen Elodie Babina Romain Pelletier Thierry Hauet Isabelle Morel Karin Tarte Florian Reizine Bruno Clment Bernard Fromenty Thomas Gicquel 《International journal of molecular sciences》2022,23(1)
Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ. 相似文献
96.
Valeska Ormazabal Estefanía Nova-Lampeti Daniela Rojas Felipe A. Zúiga Carlos Escudero Paola Lagos Alexa Moreno Yanara Pavez Camila Reyes Milly Yez Mabel Vidal Guillermo Cabrera-Vives Katherine Oporto Claudio Aguayo 《International journal of molecular sciences》2022,23(2)
Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions. 相似文献
97.
Laís Reis-das-Mercês Tatiana Vinasco-Sandoval Rafael Pompeu Aline Cruz Ramos Ana K. M. Anaissi Samia Demachki Paulo Pimentel de Assumpo Amanda F. Vidal ndrea Ribeiro-dos-Santos Leandro Magalhes 《International journal of molecular sciences》2022,23(2)
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice. 相似文献
98.
99.
Florian Rocher Tarek Alouane Graldine Philippe Marie-Laure Martin Philippe Label Thierry Langin Ludovic Bonhomme 《International journal of molecular sciences》2022,23(3)
Fusarium graminearum, the main causal agent of Fusarium Head Blight (FHB), is one of the most damaging pathogens in wheat. Because of the complex organization of wheat resistance to FHB, this pathosystem represents a relevant model to elucidate the molecular mechanisms underlying plant susceptibility and to identify their main drivers, the pathogen’s effectors. Although the F. graminearum catalog of effectors has been well characterized at the genome scale, in planta studies are needed to confirm their effective accumulation in host tissues and to identify their role during the infection process. Taking advantage of the genetic variability from both species, a RNAseq-based profiling of gene expression was performed during an infection time course using an aggressive F. graminearum strain facing five wheat cultivars of contrasting susceptibility as well as using three strains of contrasting aggressiveness infecting a single susceptible host. Genes coding for secreted proteins and exhibiting significant expression changes along infection progress were selected to identify the effector gene candidates. During its interaction with the five wheat cultivars, 476 effector genes were expressed by the aggressive strain, among which 91% were found in all the infected hosts. Considering three different strains infecting a single susceptible host, 761 effector genes were identified, among which 90% were systematically expressed in the three strains. We revealed a robust F. graminearum core effectome of 357 genes expressed in all the hosts and by all the strains that exhibited conserved expression patterns over time. Several wheat compartments were predicted to be targeted by these putative effectors including apoplast, nucleus, chloroplast and mitochondria. Taken together, our results shed light on a highly conserved parasite strategy. They led to the identification of reliable key fungal genes putatively involved in wheat susceptibility to F. graminearum, and provided valuable information about their putative targets. 相似文献
100.
Gilles Dusserre Anaïs Farrugia Thierry Cutard 《International Journal of Applied Ceramic Technology》2020,17(4):1802-1810
Geopolymer-based glass-ceramic matrix composites can be processed at room temperature and a heat treatment below 100°C leads to matrix hardening thanks to the geopolymerization mechanisms. The stabilization of the matrix into glass-ceramics is achieved via a post-curing at high temperature. This paves the way of the utilization of cost-effective liquid composite molding processes, for which all the necessary equipment is already available for processing temperature ranges related to polymer matrix composites, provided that the rheological behavior of the precursor is suitable to conveniently permeate the fibrous preform. The paper describes the thixotropic rheological behavior of a reference suspension at processing temperature (10°C-20°C) and its evolution along aging at −18°C. The changes are interpreted in terms of geopolymerization mechanisms (dissolution and polycondensation) and suspension rheology (predominance of hydrodynamic effects at high shear rate). On this basis, a phenomenological modeling framework, combining two Krieger-Dougherty equations, is proposed to build a relationship between the effective viscosity of the suspension and the phenomena involved during aging (dissolution of aluminosilicate particles) and shearing (microstructure scalar variable). 相似文献