500 research outputs found
Exosome mediated communication in cancer: melanoma and sarcoma models
No full textExosomes (EXOs) are nanovesicles of diameter ranging between 50 to 140 nm, distinguished from other cell-derived vesicles by their origin, size, morphology and composition. Their stimulatory or inhibitory signaling activities are mediated by their content (mRNAs, microRNAs and proteins) that can be transferred from the cells of origin to recipient cells, influencing the surrounding microenvironment besides cell behavior. In this study we investigated EXO-mediated communications in two cancer models, melanoma and Ewing’s sarcoma.
In view of our previous results demonstrating miR-221&222 as key factors for melanoma development and dissemination, we demonstrated that the EXO-mediated horizontal transfer of miR-222 was competent to deliver miR-222-associated properties increasing tumor malignancy.
Melanoma-purified vesicles were characterized and investigated for the functionality of miR-222 in EXO-mediated tumorigenesis. Our data showed that EXOs secreted by miR-222-overexpressing cells induced a protumorigenic program in target cells, mainly through the upmodulation of the PI3K/AKT pathway. The reverse effects were obtained with EXOs recovered after inhibition of endogenous miR-221 and miR-222 by antagomir transfections. The possible differential significance of PI3K/AKT blockade in miR-222-transduced vs control cells was assessed by using BKM120, a pan inhibitor of PI3K. Results showed the capability of miR-222 overexpression to overcome BKM120-dependent effects.
We then demonstrated the role of Ewing’s sarcoma-derived EXOs as mediators of signals involved in cancer growth, metastases and differentiation. Ewing’s sarcoma (EWS) is an aggressive childhood bone tumor characterized in the majority of cases by the presence of the fusion oncoprotein EWS-FLI1 and by high expression of the membrane glycoprotein CD99. These features, which are the necessary conditions for the pathogenesis of EWS, mediate tumor progression and maintain the cells in a dedifferentiated state. We evaluated the ability of EXOs, expressing or not CD99, to modulate the phenotype of EWS cells. We observed that the delivery of EXOs devoid of CD99 was sufficient to induce neural differentiation in EWS recipient cells through the inhibition of Notch-NF-kB signaling mediated by miR-34a overexpression.
All together these observations would provide a significant step toward new biomarker discovery and innovative therapeutic options. These data on one side support miR-222 responsibility in the exosome-associated melanoma properties, on the other the role of CD99-shRNA/miR-34a-derived EXOs to induce differentiation in EWS, thus further indicating microRNAs as potential diagnostic, prognostic and eventually therapeutic biomarkers
Pulse-Echo Monitoring of Concrete Damage and Spalling during Fire
No full textMonitoring concrete damage and spalling progression in structural members during fire tests (hot conditions) is a central but challenging task, since the high temperatures involved make difficult the implementation of most of the common Non-
Destructive evaluation methods. Hence, an advanced ultrasonic technique – Ultrasonic Pulse-Echo (UPE) – was recently adapted for real time survey in fire test, in order to evaluate the material damage during heating. The UPE technique was implemented at the cold (upper) face of concrete slabs (800x800x100 mm) heated at the bottom face according to the Standard Fire and subjected to biaxial compressive membrane loading. Different concretes were tested, with grades ranging from 40 to 60 MPa, with and without different kinds of fibre (monofilament or fibrillated polypropylene, or steel fibres). Furthermore, different load levels were applied, from 0 to 25% of the original compressive strength. During tests, spalling was generally observed in loaded plain concrete (up to 50-60 mm depth), while only slight scaling was experienced on
unloaded samples or if polypropylene fibre was added. The method proved to be very effective in recognizing the decay of the Ultrasonic Pulse Velocity (UPV) with temperature and the role played by external loading and fibre type
Strutture in acciaio esposte al fuoco: analisi meccanica e verifiche di resistenza
No full textLe strutture in acciaio sono generalmente sensibili agli effetti di un incendio a causa dell’elevata conducibilità del materiale e delle ridotte sezioni trasversali degli elementi, entrambi fattori che comportano un repentino aumento della temperatura. Una volta raggiunta la temperatura di 600°C, le proprietà meccaniche dell’acciaio risultano più che dimezzate rispetto le condizioni ordinarie. Tramite l’opportuna progettazione del sistema strutturale e di protezione è tuttavia possibile ottenere un adeguato comportamento strutturale in caso d’incendio. Tale fase di progettazione deve basarsi su un attento studio ingegneristico che, partendo da una corretta analisi del comportamento meccanico, porti alle opportune verifiche di resistenza tenendo in conto effetti rilevanti quali le azioni indirette dovute alle dilatazioni termiche impedite e il contributo dell’iperstaticità. Nel presente articolo vengono presentati gli aspetti principali dell’analisi meccanica e delle verifiche da effettuare per una struttura in acciaio esposta al fuoco
Experimental Methods for Spalling Monitoring During and After a Fire
No full textMonitoring the progress of spalling and moisture front in concrete elements subjected to heating is a challenging task, since most of the available techniques can be hardly implemented in the test furnace. This is a critical issue, because the measurement of temperature and pressure can be not sufficient to define the conditions for spalling if depth and area involved, as well as occurrence time are not known. Generally speaking, monitoring can be performed by means of Real-Time or Post-Event survey. As concerns the former approach, promising results are expected to come from ultrasonic Pulse-Echo and Ground-Penetrating Radar methods, both based on the measurement of the time delay of (ultrasonic and electromagnetic, respectively) echoes reflected by the specimen side exposed to fire. Other methods for Real-Time monitoring can be Digital Image Processing of pictures taken during heating, and Acoustic Emission. As regards spalling survey after fire, laser profilometry, optical size measurement and weighing of the collected splinters can be co-ordinately used to depict some statistical trends of the fracture process due to fire. These methods (except Acoustic Emission) have been – or will be – implemented in the case of fire tests performed on concrete slabs subjected to heating at the bottom face, and the results are discussed in the present paper
Strutture in acciaio esposte ad incendio: analisi plastica ed azioni indirette
No full textL’incendio rappresenta una condizione molto severa per tutte le tipologie strutturali ed in particolare per le strutture in acciaio qualora non vengano adottate adeguate misure di protezione. L’elevata conducibilità termica dell’acciaio, infatti, comporta un rapido aumento della temperatura e, conseguentemente, il decadimento delle proprietà meccaniche. In fase di progettazione è dunque necessario definire l’opportuno sistema di protezione e valutare, da un lato, l’effetto delle azioni indirette e, dall’altro, tutte le effettive risorse della struttura. In particolare, tener conto dell’elevata duttilità del materiale acciaio mediante l’introduzione di cerniere plastiche permette di incrementare anche notevolmente la resistenza al fuoco della struttura. Nel presente articolo si descrivono tali aspetti facendo riferimento a casi applicativi
Digital Media and Knowledge Production Within Social Movements: Insights From the Transition Movement in Italy
No full textsponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This article grounds in research activites carried out in the period 2016-2017 within the framework of the project "MAKERS- Movements as knowledge producers and learning spaces in the digital age" funded by the Scuola Normale Superiore. (Scuola Normale Superiore)status: Publishe
Spalling sensitivity test on concrete
No full textConcrete sensitivity to spalling in fire is still a critical issue, as no reliable predictive model is currently available. Hence, so far, experimental testing is the most effective means of investigation. This is the reason why an experimental setup has been designed (and discussed in the Rilem TC 256 SPF) by the authors, based on 800x800 mm concrete slabs installed in a steel frame, aimed at applying a biaxial membrane compression. Load and slab thickness can be adjusted in order to simulate the actual service conditions of concrete elements such as tunnel lining segments. The loading system is placed on a horizontal furnace pow-ered by a propane burner fitted with an automatic control system, allowing to follow the prescribed heating curve. This setup allows comparing different concrete mixes as regards their sensitivity to spalling in realistic service conditions and can be of considerable help in initial material testing for strategic infrastructures such as tunnels
Spalling Test on Concrete Slabs Under Biaxial Membrane Loading
No full textConcrete spalling is a rather complex phenomenon ensuing from the interaction of different aspects – often hard to be monitored – namely, temperature, pressure in the pores and stress. It is, in fact, commonly agreed that spalling is triggered by the mutual influence of hygro-thermal and thermo-mechanical processes. Aimed at investigating these two critical issues, an ad hoc test setup was developed at the Politecnico di Milano, based on in plane-loaded slabs. Concrete specimens of dimensions 800x800x100 mm were subjected to the Standard Fire at the intrados, while a constant biaxial compressive load was applied. Pore pressure and temperature at 6 different depths, as well as the flexural behaviour, were continuously monitored during the test. Taking advantage of this facility, an experimental campaign was carried out on one High-Performance Concrete (fc ≥ 60 MPa with silico-calcareous aggregate), without or with one among 3 different fibre types (steel fibre, monofilament or fibrillated polypropylene fibre). So far, tests on concrete without and with polypropylene fibre were carried out. Explosive spalling was observed in plain concrete only, with a remarkably homogeneous spalled layer. In all cases, the mechanical response was characterized by sagging deflection due to thermal strain followed by hogging deformation due to creep and plastic strain
Concrete spalling: Interaction between tensile behaviour and pore pressure during heating
No full textExplosive spalling is generally considered to be caused by concrete fracturing due to the interaction of (a) the pore pressure induced by moisture transport and vaporization and (b) the stress induced by thermal gradients and external loads. In order to investigate the first point, a special setup has been designed and an experimental campaign has been recently launched at the Politecnico di Milano, regarding ten different concrete mixes, characterized by different compressive strength, aggregate and fiber types
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