Analisi dinamiche in tensioni efficaci con il codice "SCOSSA"

L’incremento di pressioni interstiziali indotto da azioni sismiche in depositi sabbio-limosi determina la progressiva riduzione delle tensioni efficaci e di conseguenza della rigidezza e della resistenza dei terreni, fino a condurre alla completa liquefazione. Un metodo sviluppato per la stima di tale incremento si basa su un parametro semi-empirico, detto ‘parametro di danno’, che consente di applicare direttamente i risultati di prove cicliche di laboratorio per predire l’incremento di pressione interstiziale generato in sito dall’azione sismica. Tale procedura, implementata all’interno di un codice di calcolo non lineare, consente di effettuare analisi monodimensionali in tensioni efficaci senza adottare sofisticati modelli costitutivi del terreno. L’applicazione ad un argine danneggiato dal terremoto emiliano del 2012 ha consentito di evidenziare fenomeni di degradazione ciclica degli strati sabbiosi profondi che non sarebbe stato possibile osservare con le tradizionali analisi in tensioni totali

Un modello semplificato per la previsione dell'incremento di pressione interstiziale indotto da carichi ciclici

Le procedure che consentono la valutazione dell’incremento di pressione interstiziale indotto da azioni sismiche in terreni sabbiosi saturi si basano, tipicamente, sui risultati di prove cicliche di laboratorio a tensione o deformazione controllata. In tali procedure la storia di carico irregolare a cui è sottoposto in terreno in sito deve essere semplificata con una azione equivalente tale che produca, su provini di terreno sottoposti a prove cicliche di laboratorio, lo stesso incremento delle pressioni interstiziali atteso nel sito. In alternativa, nel caso di propagazione monodimensionale, è possibile utilizzare un unico parametro, detto ‘parametro di danno’, per modellare gli incrementi di pressione interstiziale misurati in laboratorio. Questo parametro consente di applicare direttamente i risultati di laboratorio per predire l’incremento di pressione interstiziale generato in sito da storie irregolari di tensione o deformazione dovute all’azione sismica. Tale procedura, per la sua semplicità di applicazione, consente di effettuare analisi della risposta dinamica di depositi sabbiosi saturi senza adottare sofisticati modelli costitutivi del terreno e pertanto si presta all’implementazione in codici di calcolo che operano nel dominio del tempo

List of requirements on formalisms and selection of appropriate tools

This deliverable reports on the activities for the set-up of the modelling environments for the evaluation activities of WP5. To this objective, it reports on the identified modelling peculiarities of the electric power infrastructure and the information infrastructures and of their interdependencies, recalls the tools that have been considered and concentrates on the tools that are, and will be, used in the project: DrawNET, DEEM and EPSys which have been developed before and during the project by the partners, and M\uf6bius and PRISM, developed respectively at the University of Illinois at Urbana Champaign and at the University of Birmingham (and recently at the University of Oxford)

Genetic and molecular characterization of the human osteosarcoma 3AB-OS cancer stem cell line: a possible model for studying osteosarcoma origin and stemness.

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype with 71–82 chromosomes. By comparing 3AB-OS CSCs to the parental cells, array CGH, Affymetrix microarray, and TaqMan1 Human MicroRNA array analyses identified 49 copy number variations (CNV), 3,512 dysregulated genes and 189 differentially expressed miRNAs. Some of the chromosomal abnormalities and mRNA/miRNA expression profiles appeared to be congruent with those reported in human osteosarcomas. Bioinformatic analyses selected 196 genes and 46 anticorrelated miRNAs involved in carcinogenesis and stemness. For the first time, a predictive network is also described for two miRNA family (let-7/98 and miR-29a,b,c) and their anticorrelated mRNAs (MSTN, CCND2, Lin28B, MEST, HMGA2, and GHR), which may represent new biomarkers for osteosarcoma and may pave the way for the identification of new potential therapeutic targets

Methodologies synthesis

This deliverable deals with the modelling and analysis of interdependencies between critical infrastructures, focussing attention on two interdependent infrastructures studied in the context of CRUTIAL: the electric power infrastructure and the information infrastructures supporting management, control and maintenance functionality. The main objectives are: 1) investigate the main challenges to be addressed for the analysis and modelling of interdependencies, 2) review the modelling methodologies and tools that can be used to address these challenges and support the evaluation of the impact of interdependencies on the dependability and resilience of the service delivered to the users, and 3) present the preliminary directions investigated so far by the CRUTIAL consortium for describing and modelling interdependencies

Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response

Cancer cells, which use more glucose than normal cells and accumulate extracellular lactate even under normoxic conditions (Warburg effect), have been reported to undergo cell death under glucose deprivation, whereas normal cells remain viable. As it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve new cancer therapies, in this paper we sought to identify them by using transcriptome and proteome analysis applied to an established glucoseaddicted cellular model of transformation, namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared with parental cells. Noteworthy is that the analyses performed in high-and low-glucose cultures indicate that reduction of glucose availability induces, especially in transformed cells, a significant increase in the expression of several unfolded protein response (UPR) hallmark genes. We show that this response is strictly associated with transformed cell death, given that its attenuation, by reducing protein translation or by increasing cell protein folding capacity, preserves the survival of transformed cells. Such an effect is also observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a specific substrate for the hexosamine biosynthesis pathway (HBP), to glucose-depleted cells completely prevents transformed cell death, stressing the important role of glucose in HBP fuelling to ensure UPR attenuation and increased cell survival. Interestingly, these results have been fully recognized in a human model of breast cancer, MDA-MB-231 cells. In conclusion, we show that glucose deprivation, leading to harmful accumulation of unfolded proteins in consequence of a reduction of protein glycosylation, induces a UPR-dependent cell death mechanism. These findings may open the way for new therapeutic strategies to specifically kill glycolytic cancer cells

Site response analyses for complex geological and morphological conditions: relevant case-histories from 3rd level seismic microzonation in Central Italy

The paper presents the results of 5 case studies on complex site e ects selected within the project for the level 3 seismic microzonation of several municipalities of Central Italy dam- aged by the 2016 seismic sequence. The case studies are characterized by di erent geo- logical and morphological con gurations: Monte San Martino is located along a hill slope, Montedinove and Arquata del Tronto villages are located at ridge top whereas Capitignano and Norcia lie in correspondence of sediment- lled valleys. Peculiarities of the sites are constituted by the presence of weathered/jointed rock mass, fault zone, shear wave veloc- ity inversion, complex surface and buried morphologies. These factors make the de ni- tion of the subsoil model and the evaluation of the local response particularly complex and di cult to ascertain. For each site, after the discussion of the subsoil model, the results of site response numerical analyses are presented in terms of ampli cation factors and acceleration response spectra in selected points. The physical phenomena governing the site response have also been investigated at each site by comparing 1D and 2D numerical analyses. Implications are deduced for seismic microzonation studies in similar geological and morphological conditions.Published5741–57775T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa