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Cyclin D1 and wilms tumor transcription factor-1 (WT1): potential diagnostic and therapeutic markers in small rond blue cell tumors of childhood
Wilms tumor 1 (WT1) gene, firstly cloned in 1990 in the childhood kidney cancer Wilms tumor, is a gene located on chromosome 11p13, which encodes zinc-fingers protein characterized by multiple alternative isoforms, with important regulatory functions in cell growth and development. The protein Cyclin D1 (CD1), encoded by the CCND1 gene, belongs to the highly conserved cyclin family, whose members function as regulators of CDKs (cyclin-dependent kinase) through-out the cell cycle. CD1 serves as a key sensor and integrator of extracellular signals of cells to promote progression through the G1 S phase of the cell cycle, playing several biological roles in promoting cellular proliferation/differentiation, apoptosis/survival, migration, metabolism, and neuronal regeneration.
We focused on the immunohistochemical expression profile of WT1 protein and CD1 in: i) human fetal tissues in order to provide suggestions about their role in the development of tissues and organs; ii) a large series of pediatric small round blue cell tumors, including peripheral neuroblastic tumors (neuroblastomas, ganglioneuroblastoma, ganglioneuromas), Ewing s sarcoma/pPNET (EWS/pPNET), embryonal and alveolar rhabdomyosarcomas, lymphoblastic lymphoma and Wilms tumor, to assess the potential utility of these markers in the differential diagnosis of these tumors; iii) Ewing Sarcoma derived by culture of human Ewing Sarcoma cell lines, inoculated in a group of mice, in order to establish if the immunohistochemical expression of WT1 and Cyclin D1 is comparable to that observed in human neoplastic tissues.
All cases of rhabdomyosarcoma regardless of subtype exhibited strong and diffuse cytoplasmic staining (>50% of neoplastic cells) for WT-1. In contrast, this marker was absent from lymphoblastic lymphoma (either B- or T-cell precursors), EWS/pPNET, neuroblastoma.
All cases of EWS/pPNET and the undifferentiated/poorly differentiated neuroblastomatous component of all peripheral neuroblastic tumors exhibited strong and diffuse nuclear staining (>50% of neoplastic cells) for cyclin D1. In contrast, this marker was absent from rhabdomyosarcoma (regardless of subtype) and lymphoblastic lymphoma (either B- or T-cell precursors), whereas it was only focally detected (<5% of neoplastic cells) in some cases of Wilms tumor (blastemal component) and desmoplastic small round cell tumor.
WT1 protein is a useful marker for diagnosis of malignant tumors in children and adolescents. However, it should be emphasized that not only Wilms tumor, but also other neoplasms, including desmoplastic small round cell tumor, malignant rhabdoid tumor, can express WT1 protein at nuclear level. WT1 is helpful as an additional immunomarker to conferming the diagnosis of both embryonal and alveolar rhabdomyosarcoma, being strongly and diffusely expressed in these tumors.
The present study first shows that CD1 is an additional, highly sensitive immunomarker of EWS/pPNET, along with CD99 and FLI-1. The common CD1 overexpression in pediatric/adolescent soft tissue EWS/pPNETs and its
absence in rhabdomyosarcoma (embryonal/alveolar subtypes) make this marker suitable for their differential diagnosis [160].
The expression of cyclin D1 in the Human Ewing sarcoma mouse xenograft could be the basis for new experiments on animals in order to planning new target therapies
Environmental Accounting of Marine Protected Area "Isole Ciclopi" by means of Emergy analysis
The purpose of this work is to illustrate the procedural and methodological approaches, with field-testing of materials and methods, necessary to carry out an environmental accounting study Emergy-based in a marine protected area. The study was conducted in the marine protected area "IsoleCiclopi" following a multi-year pathway, in line with the document "Environmental accounting in Italian Marine Protected Areas" (EAMPA), developed by several research groups and coordinated by Federparchi (Italian federations of Parks and Nature Reserves).In particular, the aim of EMPA project is the assessment of the ecological and economic value for the Italian marine reserves, elaborated in order to answer ministerial applications. The main purpose of this project is to detect and evaluate both biophysical and economic aspects of the reserves in order to assess the Natural Capital stocks and the Ecosystem Services generated by MPAs. The results of the research are intended to offer an innovative methodology and new points of reflection in the field of environmental evaluation and of policies
Caratterizzazione di metaboliti biologicamente attivi presenti nel miele di cardo prodotto da popolazioni siciliane di Apis mellifera
"Negli ultimi anni la nutraceutica, neologismo sincratico da nutrizione e farmaceutica coniato da Stephen De Felice nel 1989, ha suscitato un notevole interesse per gli effetti benefici che alcuni nutrienti contenuti negli alimenti hanno sulla salute. La maggior parte dei nutraceutici ha origine nel mondo vegetale, trovandosi nella frutta e nella verdura. Tra i vegetali tipici dell?ambiente mediterraneo il Carciofo e il meno conosciuto Cardo rappresentano un serbatoio naturale di composti biologicamente attivi, tra cui acidi mono- e dicaffeilchinici e flavonoidi, che rappresentano la frazione piu abbondante. Durante la fioritura del cardo in alcune aree della Sicilia e della Sardegna, si produce un miele caratteristico. La composizione del miele e alquanto variabile e dipende da numerosi fattori: origine botanica e geografica, natura del suolo, andamento climatico e specie di api che lo producono.
Lo scopo di questo lavoro e stato quello di determinare e quantificare il passaggio dei principali metaboliti biologicamente attivi presenti in foglie e polline di Cynara cardunculus L. var. altilis, al miele da esso ottenuto in purezza, in condizioni controllate, mediante l?utilizzo di due genotipi di ape (ligustica e sicula). E stata valutata sia l?influenza dell?origine (miele di cardo prodotto in purezza e commerciale) che del genotipo di ape, sui principali parametri di qualita e di caratterizzazione del miele (pH, zuccheri, minerali, fenoli e flavonoidi totali, composizione fenolica e capacita ossidante mediante i saggi DPPH, FRAP e ABTS). Inoltre, considerate le poche conoscenze che ad oggi si hanno sulle caratteristiche del miele di ape sicula e il crescente interesse per il miele prodotto da questo genotipo di ape, sono state valutate alcune caratteristiche di qualita tra cui il contenuto fenolico totale e la capacita antiossidante, ponendo a confronto mieli commerciali di varia origine botanica prodotti nella stessa zona geografica (Sicilia) da ape sicula e ape ligustica.
I risultati ottenuti hanno mostrato che vi e trasferimento di molecole biologicamente attive dalla pianta di cardo al miele da essa ottenuto e che questo e influenzato dal genotipo di ape, con il miele di ape sicula che presenta un incremento del 195% rispetto a quello di ligustica. Nella media dei fattori studiati, i composti maggiormente presenti sono risultati l?acido clorogenico (2,41 mg 100 g-1) e l?apigenin-7-O-glucuronide (2,39 mg 100 g-1). Inoltre, confrontando i mieli di cardo prodotti in purezza in condizioni omogenee e quelli commerciali dai due genotipi di ape, e emerso che la loro composizione risulta influenzata sia dall?origine (miele di cardo in purezza e commerciale) che dal genotipo di ape. Per quel che concerne le caratteristiche di qualita dei mieli commerciali siciliani di differente origine floreale (cardo, castagno, eucalipto, sulla, arancio, ferula e millefiori), prodotti da ape sicula e ligustica, queste sono state influenzate in maniera significativa oltre che dall?origine anche dal genotipo di ape. In particolare i mieli prodotti da ape sicula hanno presentato incrementi sia del contenuto di fenoli e flavonoidi totali, con valori del 71% e 51%, che del potere riducente (FRAP) e di scavenger radicale (DPPH e ABTS) del miele, con incrementi rispettivamente del 87% e 80%. La correlazione tra tutti i parametri analizzati e risultata statisticamente significativa (p < 0,05).
In conclusione i risultati sperimentali hanno evidenziato che il miele di cardo possiede un alto valore nutraceutico, soprattutto se prodotto in purezza e che l?ape nera sicula influenza significativamente la composizione del miele, producendo mieli di qualita superiore e con una maggiore capacita antiossidante rispetto all'ape ligustica.
LncRNA and circRNA expression profiles in tissues and serum exosomes of colorectal cancer patients and cell lines
In the last few years several studies demonstrated the fundamental role of non-coding RNAs (ncRNAs) in tumor onset and progression. While the involvement and the mechanism of action of microRNAs (miRNAs) have been widely investigated, little is known about long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which seem to act through a plethora of molecular mechanisms regulating essential biological processes, such as cell cycle, splicing, chromatin remodeling, apoptosis, adhesion and migration. LncRNAs are non-coding RNAs longer than 200 nucleotides, with or without 5 -cap and poly(A) tail; circRNAs are circular molecules lacking free ends and thus resistant to exonucleasic degradation, transcribed from protein-coding genes. Several evidences showed that aberrant expression of lncRNAs and circRNAs is associated with various tumors, including CRC. In our study we analysed through Real-Time PCR the expression of a set of 17 lncRNAs and 31 circRNAs selected from literature in 20 CRC tissues compared to normal adjacent tissues (NATs), and in serum exosomes of 20 CRC patients compared to 20 healthy individuals. We identified 8 ncRNAs (CCAT1, CCAT2, CDR1AS, HOTAIR, MALAT1, TUG1, UCA1 and ZEB2AS1) differentially expressed (DE) in tissues and 3 ncRNAs (circ16, TUG1 and UCA1) DE in serum exosomes. Through gene ontology analysis we verified the involvement of DE ncRNAs in pathways associated with tumor progression; we also evaluated the diagnostic accuracy of ncRNAs deregulated in serum exosomes through ROC curves, suggesting their possible application in CRC non-invasive diagnosis. We observed that inhibition of MAPK pathway, associated with CRC, altered the expression of HOTAIR, MALAT1, TUG1 and UCA1 in HCT-116 colon cancer cells treated with U0126 (MEK1/2 specific inhibitor) compared to untreated cells, suggesting a possible connection between ncRNAs and MAPKs. Also, we performed a computational analysis to identify mRNAs and miRNAs involved in CRC and characterized by correlation of expression and sequence complementarity with ncRNAs deregulated in CRC tissues. Finally, we performed in vitro functional assays by silencing UCA1 expression through ASOs in HCT-116 cells and analysed the expression of its mRNA and miRNA targets, aiming to investigate the eventual degradation triggered by the interaction between ncRNAs and their miRNA/mRNA targets. Our study provide new data about aberrant expression of ncRNAs in CRC and their involvement in carcinogenesis; further analyses will be necessary to fully understand ncRNA molecular mechanisms and to evaluate their possible application in CRC diagnosis and therapy
Analysis of the penumbra formation in sunspots
The formation of the penumbra in sunspots is a physical process which involve the coupling between the plasma and the magnetic field in different layers of the solar atmosphere. Its study requires long time series of observations carried out with high temporal, spatial, and spectral resolution. Moreover, due to few available datasets of this phase of the sunspot evolution, the physical processes at the base of the penumbra formation are still unclear. For this reason in this thesis I performed some observational analysis of the penumbra formation using high resolution data acquired during an observing campaign at the Richard B. Dunn Solar Telescope (NSO) and data taken by HMI onboard of SDO.
Two main aspects have been investigated: the location of the stable settlement of the first penumbra filaments and the transition from inverse to classical Evershed flow.
Using the high resolution images I observed the first settlement of the penumbra filaments in the two polarities of AR NOOA 11490. Before the penumbra formation the pore of the preceding polarity exhibits an annular zone characterized by a magnetic field greater than 1000 G, having an (upside down) ballerina skirt structure of the magnetic field. In this case, the penumbra starts to form in the side away from the opposite polarity, in agreement with the observations of Schlichenmaier et al. (2010). On the other hand, using the same dataset, I showed that in the following polarity of the AR NOAA 11490 a stable penumbra forms in the area facing the opposite polarity, located below an AFS, i.e. in a flux emergence region.
Moreover, considering a sample of other six ARs observed by HMI, I found that there is no preferred location for the penumbra formation.
I interpreted the formation of the penumbra as due to the field lines of the magnetic canopy, already existing at a higher level of the solar atmosphere and overlying the pore, which sink down into the photosphere and below the solar surface. In fact, in this case there is a non-zero probability of finding near-horizontal field also in the region between the two main sunspots, as shown by the recent simulations of MacTaggart et al. (2016).
Concerning the transition from inverse to classical Evershed flow, in the preceding polarity of AR NOAA 11490 I found changes in the direction of the LOS velocity field during the formation of the first penumbral sector. In about 1-3 hours the LOS velocity became coherent with the Evershed flow pattern while the penumbra was completely formed. I also found observational evidences of this transition in most of the pores of my sample observed by HMI. Therefore, I proposed a new model to explain this transition in the velocity field, based on the presence of small U-loops, which are able to drive a siphon flow toward the pore, i.e., corresponding to the inverse Evershed flow, before the penumbra formation.
The thesis is organized as follows: in Chapter 1 I provide a brief introduction on the characteristics of the solar active regions. Chapter 2 describes the main features observed in solar sunspots with particular attention to the penumbra and its formation, taking into account both the observational and theoretical point of view. The used instruments, the data and their method of analysis have been described in Chapter 3. Chapters 4 and 5 report the analysis of the data concerning the preceding and following polarities of AR NOAA 11490, respectively. The study carried out using a sample of 6 ARs observed by HMI is reported in Chapter 6. A discussion containing a possible scenario for the penumbra formation and the transition from the inverse to the classical Evershed flow is reported in Chapter 7. The conclusions drawn from the results obtained in this thesis are reported in Chapter 8
Ricerca di un segnale di neutrini cosmici dalle sorgenti gamma puntiformi delle mappe HAWC con 10 anni di dati del telescopio ANTARES e primi risultati di KM3NET
The ANTARES detector is the largest neutrino telescope in the norther hemisphere in operation since 2007, with the main scientific goal to discover astrophysical neutrino sources in the TeV-PeV energy range. In this thesis the first results of the search for a neutrino counterpart of the HAWC gamma-ray sky using the data collected by the ANTARES telescope in the period of time 2007-2017 is presented. In particular the search for a neutrino emission from the point-like sources Markarian 421 and Markarian 501 and from the HAWC gamma-ray sky has been performed. At GeV-TeV energies the gamma-ray emission due to unresolved sources, resulting from the interaction of cosmic rays with matter and photons, is the dominant component of the gamma-ray sky. In consequence of the cosmic ray interactions in our Galaxy, it is also expected that a significant component of the diffuse neutrino flux reaching the Earth has a galactic origin and can be directly related to the observed galactic gamma-rays. The sky maps used to develop the 2 years HAWC gamma-ray point source catalogue, that represents the most sensitive survey of the TeV sky at the present day, can be used to investigate the origin of the neutrino emission. In order to search for a neutrino counterpart to the HAWC gamma-ray sky, two gamma-ray point source sky maps have been considered as reference models to determine a topological and spectral energy distributions of the neutrino flux all over the sky. Even if only a fraction of the observed gamma-ray emission can be considered of hadronic origin, in this work a one-to-one correspondence between the gamma-ray and neutrino fluxes has been assumed. The sensitivity of the search for point-like neutrino sources has been estimated through MC simulations of neutrinos. The contribution to the background of atmospheric muons and atmospheric neutrinos has been also taken into account. The background from atmospheric muons has been rejected by selecting upward-going neutrino-induced tracks and applying cuts on the quality parameters of the track reconstruction algorithm. The estimator of the reconstructed energy has been used to reject atmospheric neutrinos. The search for a neutrino emission from the point-like sources has been performed using a maximum likelihood method. The search for a neutrino emission from Markarian 421 and Markarian 501 sets a sensitivity two orders of magnitude higher than the predicted neutrino fluxes. The search for an all-sky neutrino emission from the HAWC point source sky map sets an average upper limit which is a factor about 7 higher than the brightest source of the list. A less sensitive result of about 20 % has been found respect to previous ANTARES point-like source search. Since the discrepancy between the average upper limits is mainly due to the different MC productions considered in the two analyses, the differences between the MC productions are under investigations. The possibility to improve the sensitivity of the full-sky search through a stacking analysis of the point-like sources of the HAWC gamma-ray sky will be investigated in a future extension of this work. A better limit setting on the ANTARES sensitivity can be reached including also the contribution of shower-like events. Finally, a much more realistic neutrino production model will be also taken into account. To extend the ANTARES performances the KM3NeT collaboration started to build a research infrastructure in the Mediterranean Sea which will host a multi cubic kilometre scale neutrino telescope, the ARCA detector. In this thesis the software developed for the qualification and monitoring of the KM3NeT/ARCA data is presented. The analysis of the ARCA data provided the first measurement of the depth dependence of the coincidence rates induced by atmospheric muons with the two ARCA-DUs, proving also the high-performance of the ARCA detector
ABDOMINAL CALCIUM SCORE: LA TOMOGRAFIA COMPUTERIZZATA NELLA VALUTAZIONE PRE-OPERATORIA DEL RISCHIO DI DEISCENZA DELLE ANASTOMOSI CHIRURGICHE DEL COLON
La deiscenza dell anastomosi chirurgica rappresenta la più temuta e la più severa complicanza in chirurgia colon-rettale.
I processi che determinano l insorgenza della deiscenza anastomotica sono complessi e attualmente solo parzialmente conosciuti.
L aterosclerosi potrebbe essere un fattore implicato nel processo di deiscenza, in quanto spia di un alterazione del microcircolo della parete colica che interferisce con i fisiologici processi di riparazione tissutale a livello delle anastomosi.
La stima dell aterosclerosi dell aorta addominale può essere effettuata con TC attraverso il calcolo dell AAC secondo il metodo Agatston.
I nostri risultati dimostrano una differenza statisticamente significativa dei valori di calcium score tra due gruppi di pazienti "deiscenza" e "no-deiscenza".
In conclusione il calcium score può essere considerato in fase pre-operatoria un fattore di predizione del rischio di deiscenza
Teatri di figura a confronto. La tradizione viennese di Richard Teschner e quella dell'opera dei pupi. Conservazione e proposte di fruizione multimodale
La ricerca intende analizzare due particolari espressioni del teatro di figura, una afferente all area culturale mitteleuropea ovvero il teatro di Richard Teschner, e un altra prettamente mediterranea, l opera dei pupi siciliana, in particolare catanese. Le due forme, che fanno riferimento a modelli e fonti molto diversi tra loro e che si concretizzano nella realizzazione di figure e nella messa in scena di spettacoli altrettanto diversi, mostrano nonostante tutto dei punti di contatto riconducibili a quelle che sono le radici comuni di tale forma artistica e all importanza della marionetta come metafora dell essere umano declinata in maniera differente nelle varie culture e società.
La dissertazione ha un duplice scopo, da un lato quello di rintracciare nella marionetta, seppur nelle sue numerose e variegate versioni, uno strumento atto a rappresentare e superare una crisi di tipo sociale o culturale, come è accaduto nei due casi presi in esame anche se lontani tra loro sia dal punto di vista geografico che culturale; dall altro riscoprire una forma d arte che fino agli inizi del secolo scorso, in particolare fino alla Grande Guerra, è stata molto in auge in gran parte dell Europa e cui veniva riconosciuta una propria dignità, salvo poi declinare verso l oblio divenendo esclusivamente un intrattenimento per bambini e turisti, e formulare delle ipotesi di valorizzazione appropriate a far sì che il teatro di figura venga nuovamente considerato e apprezzato per la sua importanza artistica e sociale
L'Italia e le istituzioni europee: dalla CECA ai trattati di Roma.
L'argomento della tesi riguarda il ruolo svolto dall'Italia nella fase di costruzione dell'Europa. in particolare si analizza l'intervento dei principali esponenti della classe dirigente all'interno degli organismi comunitari. Dalla ricerca emerge l'attività dell'Italia soprattutto in ordine all'assetto costituzionale
H2F: a hierarchical Hadoop framework to process Big Data in geo-distributed contexts
L ampia diffusione di tecnologie ha portato alla generazione di enormi quantità di dati, o di Big Data, che devono essere raccolti, memorizzati e elaborati attraverso nuove tecniche per produrre valore nel modo migliore. I framework distribuiti di calcolo come Hadoop, basati sul paradigma MapRe-
duce, sono stati utilizzati per elaborare tali quantità di dati sfruttando la potenza di calcolo di molti nodi di cluster.
Purtroppo, in molte applicazioni di big data, i dati da elaborare risiedono in diversi data center computazionali eterogeni e distribuiti in luoghi diversi.
In questo contesto le performance di Hadoop crollano drasticamente. Per affrontare questo problema, abbiamo sviluppato un Hierarchical Hadoop Framework(H2F) in grado di pianificare e distribuire task tra cluster geograficamente distanti in modo da ridurre al minimo il tempo di esecuzione complessivo delle applicazioni.
Le nostre valutazioni sperimentali mostrano che l utilizzo di H2F migliora notevolmente il tempo di elaborazione per dataset geodistribuiti rispetto ad un semplice sistema Hadoop