Model for the seismic analysis of arch dams including interaction effects

A three-dimensional boundary element model for the seismic analysis of arch dams is presented. The soil and the dam are assumed to be viscoelastic domains the former being boundless. The water is assume to be compressible subject to small amplitude motions. The three domains are discretized into B ."E. in a single model which includes a rigurous representation of the dam-foundation rock interaction, the water-foundation rock interaction and the traveling wave effects. The response of an arch dam (The Morrow Point dam) to harmonic waves propagating vertically is studied. The important influence of the abovementioned interaction and traveling wave effects is clearly shown by computed results. These results are in contrast with sorne obtained by other authors using a F.E. model

A 3-D boundary element model for the dynamic analysis of arch dams with porous sediments

A three-dimensional boundary element technique for dynamic analysis of arch dams including dynamic interaction and sediments on the bottom of the reservoir is presented. The dam and the foundation rock are assumed to be viscoelastic domains with linear behaviour. The water is assumed to be compressible and the sediment is considered as a two-phase poroelastic material according to Biot's theory. The four domains (dam, foundation rock, water and bottom sediments) are discretized and the interaction between them is rigorously represented. The effects of sediments on the dynamic response of arch dams are evaluated for rigid and compliant foundation. Upstream, vertical and cross-stream excitation are considered. The influence of the degree of saturation of the sediment is analysed. Other modelling of the sediment as a single-phase scalar medium are considered in order to reduce the degrees of freedom of the system.Ministerio de Ciencia y Tecnología PB96-1322-C03-0

Be analysis of bottom sediments in dynamic fluid-structure interaction problems

Sediment materials play an important role on the dynamic response of large structures where fluid-soil-structure interaction is relevant and materials of that kind are present. Dam-reservoir systems and harbor structures are examples of civil engineering constructions where those effects are significant. In those cases the dynamic response is determined by hydrodynamic water pressure, which depends on the absorption effects of bottom sediments. Sediments of very different mechanical properties may exist on the bottom. A three-dimensional BE model for the analysis of sediment effects on dynamic response of those structures is presented in this paper. One of the most extended models for sediment materials corresponds to Biot’s fluid-filled poroelastic solid. The BE formulation for dynamics of poroelastic solids is reviewed including a weighted residual formulation more general and concise than those previously existing in literature. Systems consisting of water, other pressure wave propagating materials, viscoelastic solids and fluid-filled poroelastic zones, are studied. Coupling conditions at interfaces are taken into account in a rigorous way. A simple geometry coupled problem is first studied to asses the effects of sediments on its dynamic response and to determine the influence of parameters such as sediment depth, consolidation, compressibility and permeability. A fully 3-D arch dam-reservoir-foundation system where sediments and radiation damping play an important role is also studied in this paper. Obtained results show the importance of a realistic representation of sediments and the influence of their consolidation degree, compressibility and permeability on the system dynamic response.Ministerio de Ciencia y Tecnología BIA2004-03955-C02-01/0

On soil-structure interaction in large non-slender partially buried structures

This paper addresses the seismic analysis of a deeply embedded non-slender structure hosting the pumping unit of a reservoir. The dynamic response in this type of problems is usually studied under the assumption of a perfectly rigid structure using a sub-structuring procedure (three-step solution) proposed specifically for this hypothesis. Such an approach enables a relatively simple assessment of the importance of some key factors influencing the structural response. In this work, the problem is also solved in a single step using a direct approach in which the structure and surrounding soil are modelled as a coupled system with its actual geometry and flexibility. Results indicate that, quite surprisingly, there are significant differences among prediction using both methods. Furthermore, neglecting the flexibility of the structure leads to a significant underestimation of the spectral accelerations at certain points of the structure

Winkler model for predicting the dynamic response of caisson foundations

The paper presents a Winkler-based numerical model for the analysis of the dynamic response of caisson foundations. The model allows the evaluation of the impedance functions and of the foundation input motion (FIM), which can be used in the framework of the substructure approach to compute inertial soil-foundation superstructure interaction analyses. In addition, kinematic stress resultants due to seismic shear waves propagating into the soil can be estimated. The caisson is modelled as a Timoshenko beam and the soil-caisson interaction forces are derived from the analyses of the plane-strain vibration problem of an annular rigid ring embedded into the soil. The problem solution is obtained in the frequency domain exploiting the finite element approach and generic soil stratigraphies can be considered in the applications. The model, which is characterised by a very low computational effort, is validated by performing a parametric investigation, comparing results with those obtained from more rigorous BEM-FEM models of the soil-caissons systems. Finally, some applications to real caisson foundations of offshore wind turbines (OWTs) are shown to demonstrate the model accuracy in capturing the seismic response of the foundations obtained from more rigorous models

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Nef Decreases HIV-1 Sensitivity to Neutralizing Antibodies that Target the Membrane-proximal External Region of TMgp41

Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs) that target the membrane proximal external region (MPER) of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly discovered activity for Nef has important implications for anti-HIV-1 immunity and AIDS pathogenesis

Activation of mGlu3 Receptors Stimulates the Production of GDNF in Striatal Neurons

Metabotropic glutamate (mGlu) receptors have been considered potential targets for the therapy of experimental parkinsonism. One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by ionotropic glutamate receptor antagonists, such as sedation, ataxia, and severe learning impairment. Low doses of the mGlu2/3 metabotropic glutamate receptor agonist, LY379268 (0.25–3 mg/kg, i.p.) increased glial cell line-derived neurotrophic factor (GDNF) mRNA and protein levels in the mouse brain, as assessed by in situ hybridization, real-time PCR, immunoblotting, and immunohistochemistry. This increase was prominent in the striatum, but was also observed in the cerebral cortex. GDNF mRNA levels peaked at 3 h and declined afterwards, whereas GDNF protein levels progressively increased from 24 to 72 h following LY379268 injection. The action of LY379268 was abrogated by the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), and was lost in mGlu3 receptor knockout mice, but not in mGlu2 receptor knockout mice. In pure cultures of striatal neurons, the increase in GDNF induced by LY379268 required the activation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways, as shown by the use of specific inhibitors of the two pathways. Both in vivo and in vitro studies led to the conclusion that neurons were the only source of GDNF in response to mGlu3 receptor activation. Remarkably, acute or repeated injections of LY379268 at doses that enhanced striatal GDNF levels (0.25 or 3 mg/kg, i.p.) were highly protective against nigro-striatal damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice, as assessed by stereological counting of tyrosine hydroxylase-positive neurons in the pars compacta of the substantia nigra. We speculate that selective mGlu3 receptor agonists or enhancers are potential candidates as neuroprotective agents in Parkinson's disease, and their use might circumvent the limitations associated with the administration of exogenous GDNF