Experimental and numerical investigations of a river embankment model under transient seepage conditions

The evaluation of riverbank stability often represents an underrated problem in engineering practice, but is also a topical geotechnical research issue. In fact, it is certainly true that soil water content and pore water pressure distributions in the riverbank materials vary with time, due to the changeable effects of hydrometric and climatic boundary conditions, strongly influencing the bank stability conditions. Nonetheless, the assessment of hydraulic and mechanical behavior of embankments are currently performed under the simplified hypothesis of steady\u2010state seepage, generally neglecting the unsaturated soil related issues. In this paper, a comprehensive procedure for properly defining the key aspects of the problem is presented and, in particular, the soil characterization in partially saturated conditions of a suitably compacted mixture of sand and finer material, typical of flood embankments of the main river Po tributaries (Italy), is reported. The laboratory results have then been considered for modelling the embankment performance under transient seepage and following a set of possible hydrometric peaks. The outcome of the present contribution may provide meaningful geotechnical insights, for practitioners and researchers, in the flood risk assessment of river embankments

Dynamic centrifuge testing to assess liquefaction potential

A set of centrifuge tests has been carried out at ISMGEO (Italy) laboratory on models of a liquefiable soil. A natural sand from the Emilia-Romagna region in Italy was used in the tests, in order to reproduce typical ground conditions where liquefaction occurred during the seismic sequence of 2012. The models were instrumented with miniaturised accelerometers and with pore pressure and displacement transducers. Spectrum-compatible acceleration time histories were applied at the base of the model. In this way triggering of the liquefaction was detected and post-liquefaction settlements were evaluated. The paper describes with the tests carried out on free-field models. Further tests are currently ongoing to assess the seismic response of simple model structures lying on liquefiable ground. The testing programme, funded within the H2020 research project LIQUEFACT, is aimed at an experimental verification of ground improvement techniques used to mitigate the liquefaction susceptibility of fully saturated loose sands

Analysis of transient seepage through a river embankment by means of centrifuge modelling

Earthen river embankments are typically in unsaturated conditions during their lifetime and the degree of saturation within their bodies may vary significantly throughout the year, due to seasonalfluctuations of the river stage, as well as infiltrations of meteoric precipitation and evapotranspiration phenomena. Given the significant effects of partial saturation on the hydro-mechanical behaviour of soils, realistic assumptions on the actual water content distribution inside the embankments are essential forproperly modelling their response to hydraulic loadings. In this framework, centrifuge modelling is a useful tool to get insights into the evolution of saturation conditions of a water retaining structure during flood events. It allows for the direct observation of the groundwater flow process, which is hardly detectable at the prototype scale, enabling, at the same time, the validation and calibration of predictive numerical tools.In this paper, the results of a centrifuge test carried out on small-scale physical model of a compacted silty clayey sand embankment subjected to a simulated high-water event, at the enhanced gravity of 50-g, are presented and discussed. The physical model was carefully instrumented with potentiometers, miniaturized pore pressure transducers and tensiometers. Pore pressures and suctions measured during the experiment showed that the stationary flow conditions were reached only after an unrealistic hydrometric peak persistence. It therefore emerges that, for the design and/or the assessment of the safety conditions of a river embankment similar to the one tested, the simplified hypothesis of a steady-state seepage, in equilibrium with the maximum river stage expected could result, in many cases, an excessively conservative assumption

Calibration cone penetration testing in silty soils

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CSi - a joint industry project into CPTUs in silty soils

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Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion

BACKGROUND: Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. METHODOLOGY/PRINCIPAL FINDINGS: In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane. CONCLUSIONS/SIGNIFICANCE: These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions

Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion

<p>Abstract</p> <p>Background</p> <p>Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted.</p> <p>Methods</p> <p>We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17β-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling.</p> <p>Results</p> <p>Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells.</p> <p>Conclusion</p> <p>These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.</p

Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

<p>Abstract</p> <p>Background</p> <p>The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway.</p> <p>Results</p> <p>On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis.</p> <p>Conclusions</p> <p>These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.</p

17β-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin

Estrogen promotes breast cancer metastasis. However, the detailed mechanism remains largely unknown. The actin binding protein ezrin is a key component in tumor metastasis and its over-expression is positively correlated to the poor outcome of breast cancer. In this study, we investigate the effects of 17β-estradiol (E2) on the activation of ezrin and its role in estrogen-dependent breast cancer cell movement. In T47-D breast cancer cells, E2 rapidly enhances ezrin phosphorylation at Thr567 in a time- and concentration-dependent manner. The signalling cascade implicated in this action involves estrogen receptor (ER) interaction with the non-receptor tyrosine kinase c-Src, which activates the phosphatidylinositol-3 kinase/Akt pathway and the small GTPase RhoA/Rho-associated kinase (ROCK-2) complex. E2 enhances the horizontal cell migration and invasion of T47-D breast cancer cells in three-dimensional matrices, which is reversed by transfection of cells with specific ezrin siRNAs. In conclusion, E2 promotes breast cancer cell movement and invasion by the activation of ezrin. These results provide novel insights into the effects of estrogen on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers