Infiammazione e cancro: l'interazione COX-2/CA-IX promuove il potenziale invasivo e la sopravvivenza in ipossia delle cellule del cancro colon-rettale

Cyclooxygenase-2/Carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells Purpose: Cyclooxygenase-2 (COX-2) is a major mediator of inflammation, playing a pivotal role in colorectal carcinogenesis. Hypoxia is an universal hallmark of solid tumour in vivo. This investigation was prompted by the observation that in colorectal cancer cells the expression of COX-2 protein is positively correlated with that of the hypoxia survival gene Carbonic Anhydrase-IX (CA-IX). Experimental Design: Since COX-2 gene expression and activity is increased in hypoxia, and that CA-IX is expressed also in normoxia in colorectal cancer cells, we tested the hypothesis that COX-2 activity in normoxia, as well as in hypoxia may be functionally linked to that of CA-IX gene. We investigated the role of COX-2 and CA-IX in colorectal cancer cell lines. In this regard, we performed RNA interference to knockdown COX-2 gene in vitro and immunohistochemistry to evaluate the protein expression of COX-2 and CA-IX in human colon cancer tissue specimens ex vivo. Results: We found that COX-2, by PGE2 production, controls CA-IX gene expression in an ERK dependent manner. In line with this finding, we also showed that the COX-2 inhibition by a specific short harpin COX-2 RNA (shCOX-2) or by a specific drug (SC-236), down-regulated CA-IX expression in colon cancer cells. We then exposed colon cancer cells to hypoxia stimuli and found that COX-2/CA-IX interplay promoted hypoxia survival. Moreover, we also report that COX-2/CA-IX interplay triggers Matrix Metalloproteinase 2/9 (MMP-2/9) activation and enhances the invasiveness of colorectal cancer cells. Thus given our above observations, we found that CA-IX and COX-2 protein expressions correlate with more aggressive stage colorectal cancer tissues ex vivo. Conclusions: Taken together these data indicate that COX-2/CA-IX interplay promotes an aggressive phenotype (hypoxia survival and invasiveness) which can be modulated in vitro by COX-2 selective inhibition and which may play a role in determining the biological aggressiveness of colorectal tumours. Moreover, in vitro and ex vivo data also suggest that the signatures of inflammation (COX-2) and hypoxia (CA-IX) may be difficult to be disentangled in colon cancer, being both responsible for the up-regulation of the same pathways.

Francesco Platone de' Benedetti, il principe dei tipografi bolognesi. Annali tipografici (1482-1496).

This work is focused on the reconstruction of the intellectual biography of Francesco Platone de' Benedetti, prince of the Bologna's printers (1482-1486), that is the same with his typographical outputs. The research had been divided in two parts: the first, with his life, invesitigated by archive documents, and the second part, focused on the census of his editions, with a particular attention to his types. The research on the typographical types had been developed with Adobe Photoshop, that had allowed me to virtually reconstruct the cases of the Gotic and Roman types used by de' Benedetti.

Il deperimento dei geomateriali da costruzione: implicazioni sulla capacità sismica residua di edifici in CA e muratura ordinaria

This work is dedicated to the study of damaging phenomena involving reinforced concrete structures and masonry buildings and the consequences in terms of structural performances decay. In the Italian context there are many examples of structures that have already exceeded their service life, considering not only the ancient buildings but also infrastructures and R/C buildings that today are operating from more than 50th years. Climate change which is subject to the entire planet, with changing in seasonal weather and increasing in environmental pollution, is not excluded could have a harmful influence on the rate of building materials decay previously deemed as durables. If the aggressive input changes very fast, for example in a few decades, then it can also change the response of a construction material considered so far durable; in this way the knowledge about the art of good build, consolidated over the centuries, is thwarted. Hence this study is focused on the possibility to define the residual capacity for vertical or seismic loads for structures that are already at the limit of their service life, or for which is impossible to define a service life. The problem in an analysis of this kind, and that is what makes this research different from the main studies avaibles in the literature, is to keep in correlation – in a not so expensive computationally way – issues such as: - dangerous environmental inputs adequately simulated; - environmental conditions favorable to the spread of pollutants and development of the degradation reactions (decay’s speed); - link between environmental degradation and residual bearing capacity A more realistic assessment of materials residual performances that constitute the structure allows to leave the actual system for the residual load-bearing capacity estimation in which all factors are simply considered through the use of a safety factor on the materials properties.

Development of parallelizable flood inundation models for large scale analysis

Flood disasters are a major cause of fatalities and economic losses, and several studies indicate that global flood risk is currently increasing. In order to reduce and mitigate the impact of river flood disasters, the current trend is to integrate existing structural defences with non structural measures. This calls for a wider application of advanced hydraulic models for flood hazard and risk mapping, engineering design, and flood forecasting systems. Within this framework, two different hydraulic models for large scale analysis of flood events have been developed. The two models, named CA2D and IFD-GGA, adopt an integrated approach based on the diffusive shallow water equations and a simplified finite volume scheme. The models are also designed for massive code parallelization, which has a key importance in reducing run times in large scale and high-detail applications. The two models were first applied to several numerical cases, to test the reliability and accuracy of different model versions. Then, the most effective versions were applied to different real flood events and flood scenarios. The IFD-GGA model showed serious problems that prevented further applications. On the contrary, the CA2D model proved to be fast and robust, and able to reproduce 1D and 2D flow processes in terms of water depth and velocity. In most applications the accuracy of model results was good and adequate to large scale analysis. Where complex flow processes occurred local errors were observed, due to the model approximations. However, they did not compromise the correct representation of overall flow processes. In conclusion, the CA model can be a valuable tool for the simulation of a wide range of flood event types, including lowland and flash flood events.

Giovanni Francesco da Rimini Un percorso fra tradizione e rinnovamento nella pittura italiana di metà Quattrocento.

La tesi presenta l’attività di Giovanni Francesco da Rimini, pittore attivo all’incirca dal 1440 al 1470. Analizzando le varie esperienze tra Padova, Perugia, Firenze e Bologna, si ricostruisce un catalogo delle sue opere.

Studi su Cimone. Saggio di storia greca, ca. 478-461 a.C.

La monografia propone un’analisi del periodo ca. 478-461 a.C. della storia ateniese e delle vicende di Cimone figlio di Milziade entro il contesto contemporaneo. Lo studio dell’Atene, e più in generale di varie realtà elleniche affacciate sull’Egeo, negli immediati anni ‘post-persiani’ si articola in due parti: la prima ripercorre in senso cronologico le notizie, essenzialmente letterarie, disponibili in merito alle attività politiche e militari di Atene, quale guida dell’alleanza greca; la seconda trae conclusioni di respiro più ampio, fondate sull’analisi precedente, e cerca una sintesi del periodo e del personaggio nel superamento di stereotipi e condizionamenti letterari. In tale ottica si esprime una riflessione, a partire dalla scarna trattazione tucididea, sui meccanismi attraverso i quali la tradizione ha deformato e sedimentato le informazioni disponibili generando un progressivo arricchimento che ha portato alla definizione, di fatto, di una ‘era cimoniana’ che è possibile mettere in discussione in alcuni tratti essenziali. Si mira dunque a proporre una valutazione del periodo priva di alcuni elementi, in ultimo evidenti soprattutto nell’approccio plutarcheo alla materia, che appaiono alieni al contesto di riferimento per la prima parte del V secolo: i temi principali ai quali si dedica la riflessione sono quelli dell’imperialismo ateniese, del filolaconismo, della bipolarità tra democrazia e oligarchia, della propaganda politico-mitologica. Il rapporto di Atene con Sparta, con gli Ioni e con le altre realtà del mondo egeo viene letto alla luce degli indizi disponibili sul clima di incertezza e di delicati equilibri creatosi all’indomani della ritirata delle forze persiane. Il ritratto di Cimone che si propone è quello di una figura indubbiamente significativa nella politica contemporanea ma, al contempo, fortemente condizionata e talora adombrata da dinamiche in qualche modo condivise all’interno dello scenario politico ateniese, improntato alla soddisfazione di necessità e volontà che la tradizione renderà archetipiche del paradigma democratico.

Abitati rupestri e citta' fortificate nella Sicilia occidentale dai bizantini ai normanni

La ricerca effettuata, analizza in modo razionale ma contestualmente divulgativo, le dinamiche insediative che hanno caratterizzato il paesaggio della Sicilia occidentale dall'occupazione bizantina al dominio da parte dei Normanni ( 535-1194 d.C. circa ). Il volume presenta una chiara raccolta dei documenti e delle fonti letterarie che riguarda gli abitati rurali ed i borghi incastellati della Sicilia occidentale e pone l’interesse sia per la cultura materiale che per la gestione ed organizzazione del territorio. Attraverso i risultati delle attestazioni documentarie, unite alle ricerche archeologiche ( effettuate nel territorio preso in esame sia in passato che nel corso degli ultimi anni ) viene redatto un elenco dei siti archeologici e dei resti monumentali ( aggiornato fino al 2013-14 ) in funzione della tutela, conservazione e valorizzazione del paesaggio. Sulla base dei documenti rinvenuti e delle varie fonti prese in esame ( letterarie, archeologiche, monumentali, toponomastiche ) vengono effettuate alcune considerazioni sull’insediamento sparso, sull’incastellamento, sulle istituzioni e sulla formazione delle civitates. L’indagine svolta, attraverso cui sono stati individuati i documenti e le fonti, comprende anche una parziale ricostruzione topografica dei principali centri abitativi indagati. Per alcune sporadiche strutture medievali, talvolta raffigurate in fortuite stampe del XVI-XVII secolo, è stato possibile, in aggiunta, eseguire un rilievo architettonico. La descrizione degli abitati rurali e dei siti fortificati, infine, è arricchita da una serie di schede in cui vengono evidenziati i siti archeologici, i resti monumentali ed i reperti più interessanti del periodo bizantino, arabo e normanno-svevo della Sicilia occidentale.

Low-temperature thermochronological evolution of the Menderes and Alanya massifs (Turkey)

The application of two low-temperature thermochronometers [fission-track analysis and (U-Th)/He analyses, both on apatite] to various tectonostratigraphic units of the Menderes and Alanya Massifs of Turkey has provided significant new constraints to the understanding of their structural evolution. The Menderes Massif of western Anatolia is one of the largest metamorphic core complexes on Earth. The integration of the geochronometric dataset presented in this dissertation with preexisting ones from the literature delineates three groups of samples within the Menderes Massif. In the northern and southern region the massif experienced a Late Oligocene-Early Miocene tectonic denudation and surface uplift; whereas data from the central region are younger, with most ages ranging between the Middle-Late Miocene. The results of this study are consistent with the interpretation for a symmetric exhumation of the Menderes Massif. The Alanya Massif of SW Anatolia presents a typical nappe pile consisting of thrust sheets with contrasting metamorphic histories. Petrological and geochronological data clearly indicate that the tectonometamorphic evolution Alanya started from Late Cretaceous with the northward subduction of an ‘Alanya ocean’ under the Tauride plate. As an effect of the closure of the İzmir–Ankara–Erzincan ocean, northward backthrusting during the Paleocene-Early Eocene created the present stacking order. Apatite fission-track ages from this study range from 31.8 to 26.8 Ma (Late Rupelian-Early Chattian) and point to a previously unrecognized mid-Oligocene cooling/exhumation episode. (U-Th)/He analysis on zircon crystals obtained from the island of Cyprus evidentiate that the Late Cretaceous trondhjemites of the Troodos Massif not recorded a significant cooling event. Instead results for the Late Triassic turbiditic sandstones of the Vlambouros Formation show that the Mamonia mélange was never buried enough to reach the closure temperature of the ZHe radiometric system (ca. 200°C), thus retaining the Paleozoic signature of a previous sedimentary cycle.