Tunnel static behavior assessed by a probabilistic approach to the back-analysis

Problem statement: The steps of the validation procedure of the project of a tunnel are briefly illustrated in this study, starting from the geological and structural surveys on the excavation walls and the measurement of the physical and mechanical parameters during the excavation works. Unfortunately, however, the knowledge of the rock mass, which is fundamental to the project, is usually approximate before the study is started. This knowledge improves considerably once construction of the tunnel is started, when it is possible to have direct access to the rock and analyze its behavior in relation to the excavation and support works. Approach: The measurement of displacements and stresses in the rock mass and in the support structures represents a different methodology for the evaluation of the Geotechnical characteristics of a rock mass and therefore also of the support work conditions. To correctly interpret the measurements it is necessary to make use of a more complex procedure, called back-analysis, that, starting from an estimation of the unknown parameters of the rock mass obtained through a preliminary characterization, integrated and modified by sampling of the rock mass during the construction stage and by the performed stress and displacement measurements, is able to define the unknown parameters of the rock mass. Results and Conclusion: Back-analysis in engineering in the rock field occurs, however, in an uncertainty context, which complicates the problem. The preliminary estimation of the Geotechnical characteristics of the rock mass has in fact a degree of reliability that is a function of the intensity of the preliminary investigations. The performed measurements present a certain precision in relation to the various typologies of error that can occur. The final result of the back-analysis therefore also consists in the definition of the Geotechnical parameters of the rock mass that are considered to be of influence in the problem under examination, with a certain reliability and precision that is obviously greater than that relative to the initial estimation of the same parameters. The purpose of this study is to present a global approach to back-analysis in a probabilistic context that is aimed to obtain a reliable calibration of the parameters of the rock mass that are necessary to study the behavior of the support structure

On topological defect formation in the process of symmetry breaking phase transitions

By resorting to some results in quantum field theories with spontaneous breakdown of symmetry we show that an explanation based on microscopic dynamics can be given of the fact that topological defect formation is observed during the process of non-equilibrium phase transitions characterized by a non-zero order parameter. We show that the Nambu-Goldstone particle acquires an effective non-zero mass due to the boundary (finite volume) effects and this is related with the size of the defect. We also relate such volume effect with temperature effect.Comment: 12 pages, no figure

Heparan Sulfate Proteoglycans Mediate the Angiogenic Activity of the Vascular Endothelial Growth Factor Receptor-2 Agonist Gremlin.

OBJECTIVE: Heparan sulfate proteoglycans (HSPGs) modulate the interaction of proangiogenic heparin-binding vascular endothelial growth factors (VEGFs) with signaling VEGF receptor-2 (VEGFR2) and neuropilin coreceptors in endothelial cells (ECs). The bone morphogenic protein antagonist gremlin is a proangiogenic ligand of VEGFR2, distinct from canonical VEGFs. Here we investigated the role of HSPGs in VEGFR2 interaction, signaling, and proangiogenic capacity of gremlin in ECs. METHODS AND RESULTS: Surface plasmon resonance demonstrated that gremlin binds heparin and heparan sulfate, but not other glycosaminoglycans, via N-, 2-O, and 6-O-sulfated groups of the polysaccharide. Accordingly, gremlin binds HSPGs of the EC surface and extracellular matrix. Gremlin/HSPG interaction is prevented by free heparin and heparan sulfate digestion or undersulfation following EC treatment with heparinase II or sodium chlorate. However, at variance with canonical heparin-binding VEGFs, gremlin does not interact with neuropilin-1 coreceptor. On the other hand, HSPGs mediate VEGFR2 engagement and autophosphorylation, extracellular signaling-regulated kinase(1/2) and p38 mitogen-activated protein kinase activation, and consequent proangiogenic responses of ECs to gremlin. On this basis, we evaluated the gremlin-antagonist activity of a panel of chemically sulfated derivatives of the Escherichia coli K5 polysaccharide. The results demonstrate that the highly N,O-sulfated derivative K5-N,OS(H) binds gremlin with high potency, thus inhibiting VEGFR2 interaction and angiogenic activity in vitro and in vivo. CONCLUSIONS: HSPGs act as functional gremlin coreceptors in ECs, affecting its productive interaction with VEGFR2 and angiogenic activity. This has allowed the identification of the biotechnological K5-N,OS(H) as a novel angiostatic gremlin antagonist

Average patterns of spatiotemporal chaos: A boundary effect

Chaotic pattern dynamics in many experimental systems show structured time averages. We suggest that simple universal boundary effects underly this phenomenon and exemplify them with the Kuramoto-Sivashinsky equation in a finite domain. As in the experiments, averaged patterns in the equation recover global symmetries locally broken in the chaotic field. Plateaus in the average pattern wave number as a function of the system size are observed and studied and the different behaviors at the central and boundary regions are discussed. Finally, the structure strength of average patterns is investigated as a function of system size.We acknowledge the financial support of the Spanish Direcci´on General de Investigaci´on Cient´ıfica y T´ecnica, contract numbers PB94-1167 and PB94-1172.Peer Reviewe

Highly Sulfated K5 Escherichia coli Polysaccharide Derivatives Inhibit Respiratory Syncytial Virus Infectivity in Cell Lines and Human Tracheal-Bronchial Histocultures.

Respiratory syncytial virus (RSV) exploits cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The interaction between RSV and HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was used to generate a collection of sulfated K5 derivatives with a backbone structure that mimics the heparin/heparan sulfate biosynthetic precursor. The screening of a series of N-sulfated (K5-NS), O-sulfated (K5-OS), and N,O-sulfated (K5-N,OS) derivatives with different degrees of sulfation revealed the highly sulfated K5 derivatives K5-N,OS(H) and K5-OS(H) to be inhibitors of RSV. Their 50% inhibitory concentrations were between 1.07 nM and 3.81 nM in two different cell lines, and no evidence of cytotoxicity was observed. Inhibition of RSV infection was maintained in binding and attachment assays but not in preattachment assays. Moreover, antiviral activity was also evident when the K5 derivatives were added postinfection, both in cell-to-cell spread and viral yield reduction assays. Finally, both K5-N,OS(H) and K5-OS(H) prevented RSV infection in human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract. Together, these features put K5-N,OS(H) and K5-OS(H) forward as attractive candidates for further development as RSV inhibitors

Molecular Interaction Studies of HIV-1 Matrix Protein p17 and Heparin: IDENTIFICATION OF THE HEPARIN-BINDING MOTIF OF p17 AS A TARGET FOR THE DEVELOPMENT OF MULTITARGET ANTAGONISTS

Once released by HIV cells, p17 binds heparan sulfate proteoglycans (HSPGs) and CXCR1 on leukocytes causing their dysfunction. By exploiting an approach integrating computational modeling, site-directed mutagenesis of p17, chemical desulfation of heparin, and surface plasmon resonance, we characterized the interaction of p17 with heparin, a HSPG structural analog, and CXCR1. p17 binds to heparin with an affinity (Kd 190 nM) that is similar to those of other heparin-binding viral proteins. Two stretches of basic amino acids (basic motifs) are present in p17 N and C termini. Neutralization (Arg3Ala substitution) of the N-terminal, but not of the C-terminal basic motif, causes the loss of p17 heparin-binding capacity. The N-terminal heparin-binding motif of p17 partially overlaps the CXCR1-binding domain. Accordingly, its neutralization prevents also p17 binding to the chemochine receptor. Competition experiments demonstrated that free heparin and heparan sulfate (HS), but not selectively 2-O-, 6-O-, and N-O desulfated heparins, prevent p17 binding to substrate-immobilized heparin, indicating that the sulfate groups of the glycosaminoglycan mediate p17 interaction. Evaluation of the p17 antagonist activity of a panel of biotechnological heparins derived by chemical sulfation of the Escherichia coli K5 polysaccharide revealed that the highlyN,O-sulfated derivative prevents the binding of p17 to both heparin and CXCR1, thus inhibiting p17-driven chemotactic migration of human monocytes with an efficiency that is higher than those of heparin and HS. Here, we characterized at a molecular level the interaction of p17 with its cellular receptors, laying the basis for the development of heparin-mimicking p17 antagonists

Frozen spatial chaos induced by boundaries

We show that rather simple but non-trivial boundary conditions could induce the appearance of spatial chaos (that is stationary, stable, but spatially disordered configurations) in extended dynamical systems with very simple dynamics. We exemplify the phenomenon with a nonlinear reaction-diffusion equation in a two-dimensional undulated domain. Concepts from the theory of dynamical systems, and a transverse-single-mode approximation are used to describe the spatially chaotic structures.Comment: 9 pages, 6 figures, submitted for publication; for related work visit http://www.imedea.uib.es/~victo

Dynamics of a small neutrally buoyant sphere in a fluid and targeting in Hamiltonian systems

We show that, even in the most favorable case, the motion of a small spherical tracer suspended in a fluid of the same density may differ from the corresponding motion of an ideal passive particle. We demonstrate furthermore how its dynamics may be applied to target trajectories in Hamiltonian systems.Comment: See home page http://lec.ugr.es/~julya

Quasiperiodic Patterns in Boundary-Modulated Excitable Waves

We investigate the impact of the domain shape on wave propagation in excitable media. Channelled domains with sinusoidal boundaries are considered. Trains of fronts generated periodically at an extreme of the channel are found to adopt a quasiperiodic spatial configuration stroboscopically frozen in time. The phenomenon is studied in a model for the photo-sensitive Belousov-Zabotinsky reaction, but we give a theoretical derivation of the spatial return maps prescribing the height and position of the successive fronts that is valid for arbitrary excitable reaction-diffusion systems.Comment: 4 pages (figures included