Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes

Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteochondral junction in OA. We found that Grem-1, BMP-2, and BMP-4 immunostaining was detected in chondrocytes from the deep layer of cartilage and in subchondral bone of knee OA patients, and was positively correlated with cartilage damage. ELISA assays showed that bone released more Grem-1 and BMP-4 than cartilage, which released more BMP-2. In vitro experiments evidenced that compression stimulated the expression and the release of Grem-1 and BMP-4 by osteoblasts. Grem-1 was also overexpressed during the prehypertrophic to hypertrophic differentiation of murine articular chondrocytes. Recombinant Grem-1 stimulated Mmp-3 and Mmp-13 expression in murine chondrocytes and osteoblasts, whereas recombinant BMP-4 stimulated the expression of genes associated with angiogenesis (Angptl4 and osteoclastogenesis (Rankl and Ccl2). In conclusion, Grem-1 and BMP-4, whose expression at the osteochondral junction increased with OA progression, may favor the pathological remodeling of the osteochondral junction by inducing a catabolic and tissue remodeling program in hypertrophic chondrocytes and osteoblasts.     

Quelle(s) responsabilité(s) des intermédiaires techniques sur Internet?

The article tries to analyze the mechanisms of responsibility applicable to the technical intermediaries on the Internet, through the prism of the general tortuous liability. The main purpose is to define a method of application of the conditions of liability in the specific environment of Information Society. It is also aimed to identify the scope of the latter outside but also inside special regimes of liability on service providers or hosting entities.     

Evolution of salaries and the price of food and domestic fuels in the city of La Paz (1975-1985)

An analysis was performed on the variations of the food purchasing power of the average industry wage during the period comprised between 1975 and 1984 (increase of 7%), and of the minimum wage between November 1982 and August 1985 (decline of 73%). Development of retail prices in La Paz, for the main food groups, beverages and fuels, was analyzed over the same periods. Variations in work time, paid at average industry wage or at minimum wage, needed to acquire such foodstuffs, beverages or fuels, were also carefully studied. Similarly, development of the cost of calories and proteins was examined. Trends in accessibility of calories and proteins are described. Between 1975 and 1984 these included: a progressive decline in the number of foods that are sources of "cheap" or "very cheap" calories; the same trend was observed with regard to foods which are sources of "cheap" or "very cheap" proteins: A decline in their number and even the disappearance of any source of "very cheap" proteins, and an ever-increasing dependence on agro-industry and foreign imports (notably wheat). Finally, some proposals are made for the purpose of contributing to the establishment of food and nutrition planning. In particular, suggestion is made to automatically reevaluate the minimum wage on the basis of monetary inflation, in order to maintain at least the food purchasing power of the minimum wage. Maintaining this purchasing power greatly determines the nutritional status of the wage-earning population which purchases the most essential foodstuffs.     

Design and optimization of a high-efficiency array generator in the mid-IR with binary subwavelength grooves

We have designed a high-efficiency array generator composed of subwavelength grooves etched in a GaAs substrate for operation at 4.5?μm. The method used combines rigorous coupled wave analysis with an optimization algorithm. The optimized beam splitter has both a high efficiency (～96%) and a good intensity uniformity (～0.2%). The fabrication error tolerances are numerically calculated, and it is shown that this subwavelength array generator could be fabricated with current electron beam writers and inductively coupled plasma etching. Finally, we studied the effect of a simple and realistic antireflection coating on the performance of the beam splitter.     

Polymerization of a thermoset system into a thermoplastic matrix. Effect of the shear

This study concerns the morphology development of a blend based on a thermoplastic matrix with a reactive system undergoing polymerization. The system consists of 60 weight percent of polystyrene and 40 weight percent of a thermoset precursor with a low reactivity diamine (4,4′-methylenebis(2,6-diethylaniline)). Experiments were carried out in a temperature controlled oil bath and in an internal mixer. In the first case, the reaction induced phase separation process was conducted under quiescent conditions and, in the second case, under dynamic conditions. Although the kinetic study showed no noticeable difference between the static and dynamic experiments, the final morphologies obtained are quite different depending on shear. Whereas spherical particles (∼3 μm) are obtained under static conditions, irregular particles and larger dimensions characterize the morphology under shear. The classical phenomenon of droplet break up/coalescence is not applicable when an insoluble fraction is present. In the vicinity of the gelation time, the particles tend to aglomerate in an irreversible way and so the process of shape relaxation leading to spherical particles becomes impossible.     

The provision of urban parks: an empirical test of spatial spillovers in an urban area using geographic information systems

Green spaces provide various amenities ranging from ecological services to recreational benefits. They are strategic for municipalities both for households and business attractiveness. While the social demand for urban parks is increasing, information about their provision and guidance regarding the efficiency of local policies remain scarce. In this paper, we investigate the existence and the nature of spatial spillovers for the provision of urban parks in 93 municipalities in the urban area of Angers, France. We use geographic information systems to obtain land use data. We estimate a reaction function, with interactions between cities and their provision of urban parks. For this end, we shall apply spatial econometric techniques. We find positive autocorrelation among municipalities. A 10% rise in the level of parks in neighboring municipalities leads to a 3.6% increase ceteris paribus. From the empirical perspective, we cannot reject the hypothesis of mimetic behaviour among municipalities.     

Evaluation of the Chiral DIANANE Backbone as Ligand for Organolithium Reagents

Novel endo,endo‐2,5‐diaminonorbonane‐derived tertiary C₂‐symmetrical diamines were synthesized via the one‐pot reductive amination of enantiomerically pure norbornane‐2,5‐dione. These ligands were applied to various catalytic reactions such as asymmetric deprotonation, asymmetric bromine‐lithium exchange, and enantioselective addition of aryl‐ and allkylithium reagents to aromatic aldimines.     

Hydroxamic acids as potent inhibitors of Fe(II) and Mn(II) E. coli methionine aminopeptidase: biological activities and X-ray structures of oxazole hydroxamate-EcMetAP-Mn complexes

New series of acids and hydroxamic acids linked to five-membered heterocycles including furan, oxazole, 1,2,4- or 1,3,4-oxadiazole, and imidazole were synthesized and tested as inhibitors against the Fe(II) , Co(II) , and Mn(II) forms of E. coli methionine aminopeptidase (MetAP) and as antibacterial agents against wild-type and acrAB E. coli strains. 2-Aryloxazol-4-ylcarboxylic acids appeared as potent and selective inhibitors of the Co(II) MetAP form, with IC(50) values in the micromolar range, whereas 5-aryloxazol-2-ylcarboxylic acid regioisomers and 5-aryl-1,2,4-oxadiazol-3-ylcarboxylic acids were shown to be inefficient against all forms of EcMetAP. Regardless of the heterocycle, all the hydroxamic acids are highly potent inhibitors and are selective for the Mn(II) and Fe(II) forms, with IC(50) values between 1 and 2 μM. One indole hydroxamic acid that we previously reported as a potent inhibitor of E. coli peptide deformylase also demonstrated efficiency against EcMetAP. To gain insight into the positioning of the oxazole heterocycle with reversed substitutions at positions 2 and 5, X-ray crystal structures of EcMetAP-Mn complexed with two such oxazole hydroxamic acids were solved. Irrespective of the [metal]/[apo-MetAP] ratio, the active site consistently contains a dinuclear manganese center, with the hydroxamate as bridging ligand. Asp 97, which adopts a bidentate binding mode to the Mn2 site in the holoenzyme, is twisted in both structures toward the hydroxamate bridging ligand to favor the formation of a strong hydrogen bond. Most of the compounds show weak antibacterial activity against a wild-type E. coli strain. However, increased antibacterial activity was observed mainly for compounds with a 2-substituted phenyl group in the presence of the nonapeptide polymyxin B and phenylalanine-arginine-β-naphthylamide as permeabilizer and efflux pump blocker, respectively, which boost the intracellular uptake of the inhibitors.     

Optical transmission as a fast and non‐destructive tool for determination of ethylene‐co‐vinyl acetate curing state in photovoltaic modules

Poly(ethylene‐co‐vinyl acetate) (EVA) is the primary polymer used for encapsulation of photovoltaic (PV) modules. Its degree of cross‐linking (gel content) is taken as a major quality reference. The EVA gel content is normally measured by Soxhlet extraction and more recently also by Differential Scanning Calorimetry (DSC). The DSC method is proven here to be fast and effective but is, as the Soxhlet extraction method, destructive to the PV module. With the aim of developing a fast and non‐destructive method to determine the gel content, a number of analytical techniques are presented. The most promising method is ultraviolet/visible/near‐infrared (UV/Vis/NIR) optical transmission. The measured diffuse transmission reflects the EVA crystallite size, which is related to the EVA gel content. This opens the possibility to apply an in‐line analysis of every PV module immediately after the lamination step and could significantly contribute to the process quality control that is needed in future high‐throughput production lines of PV modules. Copyright © 2011 John Wiley & Sons, Ltd.