Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis

The αvβ6 integrin plays a key role in the activation of transforming growth factor-β (TGFβ), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvβ6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and diseaserelated end points. Here we report, GSK3008348 binds to αvβ6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFβ signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvβ6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvβ6, induces prolonged inhibition of TGFβ signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy

An Ru-based catalytic membrane reactor for dry reforming of methane : its catalytic performance compared with tubular packed bed reactors

The methane reforming with CO2 seems to be a promising reaction system useful to reduce the greenhouse contribution of both gases into the atmosphere. On this basis, and considering the potentiality of this reaction system, the dry reforming reaction has been carried out in an Ru-based ceramic tubular membrane reactor, in which two Ru depositions have been performed using the co-condensation technique. Experimental results in terms of CH4 and CO2 conversion versus temperature during time are presented, as well as product selectivity and carbon deposition. These experiments have also been carried out using a traditional reactor. A comparison with literature data regarding dry reforming reaction is also provided. Experimental evidence points out a good catalyst activity for the methane dry reforming reaction, confirming the potentiality of a catalytic membrane applied to the reaction system. © 2003 Elsevier B.V. All rights reserved. 10.1016/S0920-5861(03)00202-

PISA: PI SOFTWARE ARCHITECTURE FOR INTEGRATED SATELLITE PAYLOAD CONTROLLERS

With the growing amount of data produced by instruments and the increasing importance of the payload element that delivers the added value of the missions, a satellite can be regarded as a distributed system with a platform integrating all the traditional on-board control functions (Attitude and Orbit Control and Data Handling Control) and collaborating with the payload through the spacecraft bus. In PISA, we investigate tools and methods to develop a payload controller based on a single embedded computer integrating instrument control software components developed by several PI teams. A hardware demonstrator based on PowerPC running RTAI Linux is also presented

Distribution of joints in the hinge-line culmination of foreland-verging overturned anticlines: An example from the Montagna dei Fiori structure in the Central Apennines of Italy

The distribution of joints, veins and shear fractures in the Montagna dei Fiori overturned anticline is here reported. Two joint sets, longitudinal and transverse to the NNW-SSE anticline axial trend, and a conjugate system of shear fractures, are recognized. The transverse and longitudinal joint sets have a pre-folding development likely related to the foreland/foredeep flexure. The transverse joints were reopened during layer-parallel shortening along with the development of the shear fractures. Then, during syn-folding outer-arc extension and hinge-line culmination fold-axial parallel extension, both the longitudinal and transverse joints were enhanced and reactivated, respectively.© Cambridge University Press 201