Modulation of αVβ6 integrin in osteoarthritis-related synovitis and the interaction with VTN(381–397 a.a.) competing for TGF-β1 activation

Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381–397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-β1 activation were investigated. A competition study determined the interaction of VTN_{(381–397 a.a.)} with α_Vβ₆ integrin. Subsequently, the presence of α_Vβ₆ integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, β₆ was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, β₆ expression was increased under TGF-β1 stimulation; hence, a TGF-β bioassay was applied. We observed that α_Vβ₆ could mediate TGF-β1 bioavailability and that VTN_{(381–397 a.a.)} could prevent TGF-β1 activation by interacting with α_Vβ₆ in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS–MS, confirming the increased expression of VTN_{(381–397 a.a.)} in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN_{(381–397 a.a.)} in osteoarthritis but also in other rheumatic diseases. This fragment interacts with α_Vβ₆ integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-β1 precursor in human FLSs.Subject terms: Osteoarthritis, Cell culture     

The Baire Category Property and Some Notions of Compactness

We work in set theory without the axiom of choice: ZF. We showthat the axiom BC: Compact Hausdorff spaces are Baire, is equivalentto the following axiom: Every tree has a subtree whose levelsare finite, which was introduced by Blass (cf. [4]). This settlesa question raised by Brunner (cf. [9, p. 438]). We also showthat the axiom of Dependent Choices is equivalent to the axiom:In a Hausdorff locally convex topological vector space, convex-compactconvex sets are Baire. Here convex-compact is the notion whichwas introduced by Luxemburg (cf. [16]).     

A second-order accurate material-order-independent interface reconstruction technique for multi-material flow simulations

A new, second-order accurate, volume conservative, material-order-independent interface reconstruction method for multi-material flow simulations is presented. First, materials are located in multi-material computational cells using a piecewise linear reconstruction of the volume fraction function. These material locator points are then used as generators to reconstruct the interface with a weighted Voronoi diagram that matches the volume fractions. The interfaces are then improved by minimizing an objective function that smoothes interface normals while enforcing convexity and volume constraints for the pure material subcells. Convergence tests are shown demonstrating second-order accuracy. Static and dynamic examples are shown illustrating the superior performance of the method over existing material-order-dependent methods.     

A high‐throughput bioanalytical platform using automated infusion for tandem mass spectrometric method optimization and its application in a metabolic stability screen

Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the bioanalytical method of choice to support plate‐based, in vitro early ADME (Absorption, Distribution, Metabolism and Excretion) screens such as metabolic stability (Metstab) assessment. MS/MS method optimization has historically been the bottleneck in this environment, where samples from thousands of discrete compounds are analyzed on a monthly basis, mainly due to the lack of a high‐quality commercially available platform to handle the necessary MS/MS method optimization steps for sample analysis by selected reaction monitoring (SRM) on triple quadrupole mass spectrometers. To address this challenge, we recently developed a highly automated bioanalytical platform by successfully integrating QuickQuan? 2.0, a unique high‐throughput solution featuring MS/MS method optimization by automated infusion, with a customized in‐house software tool in support of a Metstab screen. In this platform, a dual‐column setup running parallel chromatography was also implemented to reduce the bioanalytical cycle time for LC/MS/MS sample analysis. A set of 45 validation compounds was used to demonstrate the speed, quality and reproducibility of MS/MS method optimization, sample analysis, and data processing using this automated platform. Metstab results for the validation compounds in microsomes from multiple species (human, rat, mouse) showed good consistency within each batch, and also between batches conducted on different days. We have achieved and maintained a monthly throughput of 1300 compound assays representing 500 discrete compounds per instrument per month on this platform, and it has been used to generate metabolic stability data for more than 25 000 compounds to date with an overall success rate of more than 95%. Copyright © 2009 John Wiley & Sons, Ltd.     

Invertibility of functional Galois connectionsInversibilité des correspondances de Galois fonctionnelles

We consider equations of the form Bf=g, where B is a Galois connection between lattices of functions. This includes the case where B is the Fenchel transform, or more generally a Moreau conjugacy. We characterize the existence and uniqueness of a solution f in terms of generalized subdifferentials, which extends K. Zimmermann's covering theorem for max-plus linear equations. To cite this article: M. Akian et al., C. R. Acad. Sci. Paris, Ser. I 335 (2002) 883–888.     

Das amtlich empfohlene Verfahren zum papierchromatographischen Nachweis von Malvin in Rotwein und Traubensaft

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