P-wave and surface wave survey for permafrost analysis in alpine regions

We discuss the results of seismic survey to delineate temporal and spatial changes of frozen layer in Alpine environments. The seismic characterization allows us to detect changes of soil deformability properties related to the temperature effect on subsoi

Effect of Electro-kinetic Consolidation on Fine Grained Dredged Sediments

Abstract The management of the huge amount of dredged sediments is an important issue to be solved worldwide, and dewatering is by far the most critical step when fine grained sediments are involved. Different technologies have been proposed in time to speed up the process. Even though electro-kinetic treatment is in principle one of them, it has not been implemented yet at an industrial scale, and only few trial applications are known. For such a reason, a multidisciplinary research activity is ongoing at the University of Napoli Federico II in the framework of the EU commitment ROSE with the aim to analyse the effectiveness and feasibility of such a technology from the lab to the site scale. In this paper, some evidences stemming from lab tests are presented. The results indicate that the application of low voltages improves the mechanical behaviour of the tested soil. In this case, however, the improvement is due more to a change in microstructure than to a decrease in void ratio

a pore water pressure model calibration based on in situ test results

Abstract This paper proposes a procedure for the calibration of a simplified pore water pressure model implemented in 1D effective stress dynamic analyses. The calibration procedure is based on the cyclic strength of the soils as quantified using empirical correlations with in-situ tests, CPT and SPT. Specific relationships have been directly defined among the parameters of the pore water pressure model and the results of in-situ tests. All the steps for the definition of these relationships are described in detail. The proposed calibration procedure has been used to simulate the seismic response of two well-documented reclaimed sites where widespread liquefaction occurred: Port Island, in Kobe (Japan) and Treasure Island in California (US), struck by the 1995 Kobe and the 1989 Loma Prieta earthquakes, respectively. The results of the analyses have been compared to the actual site response as recorded by downhole acceleration arrays, showing that the proposed approach leads to a good estimate of the site response. Guidelines for calibration of the proposed model are finally provided, and the advantages and limitations of its use are discussed in detail

Effect of the pore fluid salinities on the behaviour of an electrokinetic treated soft clayey soil

Dredging activities of harbours and rivers are becoming very important in many countries all over the world and, as a consequence, the disposal of dredged sediments is a critical concern from an environmental point of view. In order to facilitate the disposal or the reuse of large volume of dredged soils, usually under-consolidated and with a high water content, an electrokinetic treatment can be adopted with the goal to dewater and strengthen the sediments. This paper presents the results of some electrokinetic tests performed on reconstituted clayey specimens at different pore fluid salinities (0.2 < sc < 30 g/l) treated with electrokinetic (EK) technique. The results indicate that the presence of small quantities of salts in the pore fluid enhances the electro-osmotic consolidation. On the contrary, for high salt concentrations of the pore fluid the electro-osmotic dewatering is significantly reduced. The mechanical behaviour of treated specimens has been investigated at the micro (SEM) and macro scale (triaxial and oedometer tests). The experimental results highlighted the relevant and expected contribution of the pore fluid characteristic on the effectiveness of the treatment as ground improvement technique

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma

Background: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6- methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity. Methods: Tinostamustine has been tested in models of GBM by using 13 GBM cell lines and seven patient-derived GBM proliferating/stem cell lines in vitro. U87MG and U251MG (MGMT negative), as well as T98G (MGMT positive), were subcutaneously injected in nude mice, whereas luciferase positive U251MG cells and patient-derived GBM stem cell line (CSCs-5) were evaluated the orthotopic intra-brain in vivo experiments. Results: We demonstrated that tinostamustine possesses stronger antiproliferative and pro-apoptotic effects than those observed for vorinostat and bendamustine alone and similar to their combination and irrespective of MGMT expression. In addition, we observed a stronger radio-sensitization of single treatment and temozolomide used as control due to reduced expression and increased time of disappearance of γH2AX indicative of reduced signal and DNA repair. This was associated with higher caspase-3 activation and reduction of RT-mediated autophagy. In vivo, tinostamustine increased time-to-progression (TTP) and this was additive/synergistic to RT. Tinostamustine had significant therapeutic activity with suppression of tumor growth and prolongation of DFS (disease-free survival) and OS (overall survival) in orthotopic intra-brain models that was superior to bendamustine, RT and temozolomide and showing stronger radio sensitivity. Conclusions: Our data suggest that tinostamustine deserves further investigation in patients with glioblastoma

NUMERICAL ANALYSIS ON SHALLOW FOUNDATIONS LATERAL DISCONNECTION

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The small molecule ephrin receptor inhibitor, GLPG1790, Reduces renewal capabilities of cancer stem cells, showing anti-tumour efficacy on preclinical glioblastoma models

Therapies against glioblastoma (GBM) show a high percentage of failure associated with the survival of glioma stem cells (GSCs) that repopulate treated tumours. Forced differentiation of GSCs is a promising new approach in cancer treatment. Erythropoietin-producing hepatocellular (Eph) receptors drive tumourigenicity and stemness in GBM. We tested GLPG1790, a first small molecule with inhibition activity versus inhibitor of various Eph receptor kinases, in preclinical GBM models using in vitro and in vivo assays. GLPG1790 rapidly and persistently inhibited Ephrin-A1-mediated phosphorylation of Tyr588 and Ser897, completely blocking EphA2 receptor signalling. Similarly, this compound blocks the ephrin B2-mediated EphA3 and EphB4 tyrosine phosphorylation. This resulted in anti-glioma effects. GLPG1790 down-modulated the expression of mesenchymal markers CD44, Sox2, nestin, octamer-binding transcription factor 3/4 (Oct3/4), Nanog, CD90, and CD105, and up-regulated that of glial fibrillary acidic protein (GFAP) and pro-neural/neuronal markers, βIII tubulin, and neurofilaments. GLPG1790 reduced tumour growth in vivo. These effects were larger compared to radiation therapy (RT; U251 and T98G xenografts) and smaller than those of temozolomide (TMZ; U251 and U87MG cell models). By contrast, GLPG1790 showed effects that were higher than Radiotherapy (RT) and similar to Temozolomide (TMZ) in orthotopic U87MG and CSCs-5 models in terms of disease-free survival (DFS) and overall survival (OS). Further experiments were necessary to study possible interactions with radio- and chemotherapy. GLPG1790 demonstrated anti-tumor effects regulating both the differentiative status of Glioma Initiating Cells (GICs) and the quality of tumor microenvironment, translating into efficacy in aggressive GBM mouse models. Significant common molecular targets to radio and chemo therapy supported the combination use of GLPG1790 in ameliorative antiglioma therapy