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L'officina de I Viceré. La genesi del romanzo attraverso l'epistolario di Federico De Roberto
No full textLa Tesi si propone di analizzare la complessa genesi de I Viceré attraverso l epistolario di Federico De Roberto e il suo dialogo con numerosi corrispondenti (Giovanni Verga, Luigi Capuana, l editore Carlo Chiesa, Ferdinando Di Giorgi, e molti altri). Gli anni presi in esame sono in particolare quelli che vanno dal 1891 al 1895. Nel complesso l epistolario di De Roberto in quest arco temporale ci restituisce la faticosa genesi del romanzo dalla parte creativa della scrittura a quella pratica che riguardava le scelte editoriali e tipografiche
Estimation of dicarbonyl compounds intake in Italy and their potential role against food spoilage/pathogenic bacteria
No full textFoods, from the earliest times, are subjected to man-made modifications to ensure microbiological safety, enzymatic inactivation, destruction of toxic substances, and optimization of storage time. An undisputable role in making the food softer, tasty and preservable over time is exerted by heat treatment. It is during this phase that a series of chain reactions, known like Maillard's reaction, are triggered. During this reaction, products that affect the flavor, color and aroma of foods are formed. Among these, glyoxal, methylglyoxal and 3-deoxyglucosone are of particular importance.
These compounds are present in food, have antimicrobial activity, are promoters of advanced glycation end products formationand also have toxic effects in in vitro and in vivo studies.
Research activity carried out during Ph.D. study had a common thread: increasing knowledge on 1,2-dicarbonyl compounds.
In this field, the overall aims of this thesis work were: assessment of the content of dicarbonyl compounds in Italian food; assessment of their dietary intake; study of formation/degradation of dicarbonyl compounds using food model systems; evaluation of antimicrobial activity of the main dicarbonyl compounds; study of the interaction between the dicarbonyl compounds and the nutrients present in the microbiological culture media, both in the presence and absence of the microorganism.
The results obtained by the survey on Italian food show that the concentration is variable and the predominant 1,2-dicarbonyl compounds is 3-deoxyglucosone.
The estimation on dietary intake with a Total Diet Study-like investigation, have brought new evidence to assert that the ingestion with foods is high especially for infants (0-2 years) and children (3-9 years).
The results obtained with the model systems show that time, temperature and ingredients have a strong influence on the formation of the compounds and that it is possible to reduce the level of 1,2-dicarbonyl compounds.
The results of antimicrobial assays lead us to conclude that dicarbonyl compounds, especially GO and MGO, could have a role in the microbial stability of foods, although food composition may strongly influence their availability to act as antimicrobials.
The results obtained by the study of the interaction between the dicarbonyl compounds and the nutrients present in the culture media allow us to assert that the 1,2-dicarbonyl compounds are degraded very quickly when they come into contact with bacteria.
The results obtained outline a framework of knowledge that is a prelude to subsequent important developments
Microwave accelerating structures: an innovative parallel coupled electron LINAC
No full textParticle accelerators are employed in many fields of the physics, engineering and medicine science. Although the idea of acceleration of charged particles by means of time varying electromagnetic field is an almost century old, the research and development in this field is active more than ever. An efficient particle accelerator gives the opportunity to reach energy levels not yet achieved and allows the study of the deepest laws of the physics. Also a better performance of the particle accelerators is desirable in order to develop compact table-top machine for medical or industrial purpose. The work here presented takes place in this framework. A parallel coupled electron LINAC has been studied for high gradient operation in the X-band frequency. This kind of device can address some issues of high gradient accelerating LINAC. Due to decoupled propagation axes for RF power and beam it is possible to increase the structure shunt impedance without affecting the cell to cell coupling, combining the advantages of travelling and standing wave structures. Besides in case of a breakdown only the energy stored in one cell is involved in the discharge process and not the total energy stored of the section, thus the damages caused by the breakdown event are expected to be smaller. Following a discussion on how the proposed configuration was conceived, full wave simulations were carried out to numerically validate the idea and to optimize the single cell in order to minimize the probability of breakdowns. After a successful cold simulation a beam dynamics analysis has been done in order to estimate the properties of the beam moving inside the device. Due to the small irises dimension the transverse wakefield can be source of instability for the bunch propagation. Therefore this issue has been investigated by means of numerical methods. Finally, the problem of the beam alignment with respect to the accelerating section is addressed and the results of a device suitable to beam position measurement are presented
Genome instability in colorectal cancer
No full textFour main forms of genomic instability have been described in colorectal cancer (CRC): microsatellite instability (MSI), chromosomal instability (CIN), epigenome abnormalities (CIMP), and hypermutation-ultramutation.
The present thesis was focused on the two better characterized forms of genome instability: MSI and CIN. The aim of the present work was to set up a new classification based on MSI and CIN and to analyze gene expression profiles of the newly defined groups.
Microsatellite testing classifies tumor samples in two fundamental types: microsatellite-instable (MSI) and microsatellite-stable (MSS) tumors. This classification is well-established according to routine methodology and widely accepted guidelines (Boland et al., 1998). In the present thesis a detailed mutational profile analysis was performed for DNA mismatch repair (MMR) genes, the catalytic subunit of proofreading polymerases (POLE and POLD1) and a selected group of 50 among oncogenes and tumor suppressors, for a more accurate molecular description of MSI tumors.
Classification based on chromosomal instability is much less standardized and affected by some technical difficulties. In the present thesis, the recent proposal about the use of somatic broad copy number abnormalities (BCNAs) (Barresi et al., 2017) was adopted in order to identify and sub-classify CRC tumors. According to the proposed methodology and to new criteria established in the present work, MSS tumors were subdivided into high-BCNA (HB) and low-BCNA (LB) tumors. A mutational profile analysis - with the same methodology used for MSI tumors was also applied to the LB group.
A further step of the present work was to correlate the classification based on microsatellite status and on the number of BCNAs with gene expression profiles from cancer samples.
HB tumors showed upregulation of intestinal epithelial genes, such as NOX1, AREG, EREG.
LB tumors and MSI tumors shared a pattern of upregulation of REG4, AGR2, SPP1, CD55, MUC5B, although expression of such genes was higher for MSI samples. Upregulation of these genes had previously been described for mucinous tumors. Indeed, LB and MSI groups were enriched for mucin-producing tumors.
In conclusion, taking into account the number of BCNAs, along with MSI status and with the mutational profile, two groups of MSS samples can be distinguished: HB tumors, characterized by the expression of a subset of epithelial genes, some of them involved in EGF signaling; and LB tumors, enriched for mucin-producing tumors, which resemble MSI tumors for what concerns upregulation of a subset of genes involved in the colon mucus barrier and other cell-precursor markers
Le recenti politiche processuali in materia di spese giudiziali civili
No full textIl progetto di ricerca di Rosario Di Grazia si prefigge l obiettivo d indagare sull evoluzione della disciplina delle spese processuali (lato sensu considerate ed includenti, così, anche le fattispecie di sanzione pecuniaria per abuso del processo) e dei criteri fondanti la medesima disciplina (soccombenza, causalità, interesse, abuso del processo), tentando di individuare i limiti di compatibilità della mutata ratio di essa con i principi di rango costituzionale nazionale e sovranazionale posti a tutela del diritto di azione e di difesa. Oggetto d'indagine è anche il progressivo aumento delle voci di spesa di cui alla parte II del D.P.R. 30 maggio 2002, n. 115 (meglio conosciuto come Testo Unico in materia di spese di giustizia )
PPGIS-based Multi Criteria Decision Analysis for the Evaluation of Transport Projects Scenarios
No full textThe decision-making process of transport projects is very complex, especially for public administrations which have to take into account often incomparable criteria of judgment. In addition, in order to achieve a good social sharing and robustness of the decision, policy makers have to include in the process not only the transport planning experts but also the stakeholders of the community.
The purpose of this study is to propose an evaluation framework that supports the decision making process able to allow public participation in the assessment of transport design scenarios while at the same time ensuring a high level of technical quality of the final decision. The framework will include a method to analyze monetary and non-monetary parameters that will be easily understandable for all decision makers. It will be based on the application of Multi Criteria Decision Analysis (MCDA) techniques, an evaluation process that can take into account different quantitative and qualitative objectives and criteria; in order to favor public participation, the implementation of this technique will take advantage of Geographic Information System (GIS) for its ability to easily represent the impact of spatially based alternative project scenarios. Different case studies will be analyzed in order to assess the level of implementation of the three main ingredients of the framework: Multi Criteria Analysis, GIS and Public Participation
Strutture portuali innovative e interazione col moto ondoso per la produzione di energia
No full textIl mare rappresenta una inesauribile fonte di energia rinnovabile, di particolare interesse economico per i territori che si affacciano lungo le coste, grazie ad una tariffa particolarmente incentivante proposta da alcuni Paesi. Lo sfruttamento di questa fonte di energia richiede lo sviluppo di tecnologie adatte alla fonte di energia e al sito di interesse.
Tra le varie forme di energia, quella relativa al moto ondoso viene convertita in energia elettrica attraverso l impiego dei diversi sistemi di produzione noti come Wave Energy Converter WEC. Le tipologie di WEC brevettate sono molteplici, ognuna con il proprio principio di funzionamento ed ognuna adatta ad una specifica installazione. Una delle applicazioni prevede l istallazione dei sistemi WEC onshore, nei porti. Ipotizzare l istallazione di un sistema WEC nei porti modifica l ottica di inquadramento degli stessi da infrastruttura intermodale di trasporto a infrastruttura verde. Finora, i porti sono stati considerati infrastrutture in cui confluiscono e hanno continuità varie vie di comunicazione fluvio-marittime, terresti e aeree. Oggi, i porti verdi e le infrastrutture cosiddette smart assumono un interesse sempre più rilevante ai fini di una green-strategy. Essi rappresentano una rinnovata sostenibilità ambientale delle mobilità e delle attività interportuali.
L attività svolta favorisce lo sviluppo dei sistemi WEC, contribuendo alle valutazioni sull efficienza in condizioni reali. Particolare attenzione è rivolta ai dispositivi Oscillating Water Column OWC che hanno il vantaggio di essere integrabili nelle dighe portuali a parete verticale. Gli OWC sfruttano le oscillazioni del pelo libero del moto ondoso mediante la compressione e decompressione dell aria in una camera stagna che viene veicolata verso una turbina in grado di funzionare in entrambe le direzioni del moto.
La presente ricerca è stata condotta mediante modellazione fisica, con l obiettivo di migliorare l efficienza del sistema valutando vantaggi e criticità del dispositivo. Nel dettaglio, è stato analizzato il funzionamento dei sistemi OWC simulando, per semplicità, la perdita di carico dovuta alla turbina mediante un orifizio, un restringimento inserito in un condotto verticale sopra la camera d aria. Il funzionamento del sistema è stato esaminato dal punto di vista strutturale e idrodinamico attraverso le valutazioni sul periodo proprio di oscillazione del sistema, sulla riflessione del sistema, sulle pressioni e sulle forze agenti sulla struttura. In dettaglio, dalla modellazione a grande scala è stato possibile valutare il diametro dell orifizio ottimale, che provoca la minor riflessione possibile.
Note le difficoltà di riprodurre i modelli a grande scala, sono stati valutati gli effetti di scala su un OWC a piccola scala, progettato a partire dalla modellazione a grande scala.
I parametri geometrici sono stati indagati nella modellazione a piccola scala valutando la loro influenza sulla riflessione. È stato dunque possibile definire una configurazione ottimale del sistema.
Il lavoro svolto ha come fine ultimo quello di favorire la progettazione di un sistema OWC da inserire presso un sito campione, scelto lungo le coste della Sicilia. L OWC è stato modellato a piccola scala sulla base delle condizioni d onda e morfologiche del sito. Il dimensionamento del caso studio è stato eseguito sulla base delle valutazioni del periodo proprio del sistema, della riflessione, delle pressioni e dei carichi. Da tale applicazione è stato altresì possibile valutare il problema del rumore provocato dall attivazione della turbina in fase di esercizio, proponendo una soluzione che riduce il livello sonoro a valori compatibili con le attività previste nel porto. Inoltre, è stato possibile massimizzare il rendimento del dispositivo OWC al caso studio. Infine è stata verificata la stabilità strutturale ed è stata eseguita un analisi economica sull istallazione di un OWC in un porto
Variational inequalities and networks for organ transplants and for humanitarian organizations
No full textIn this thesis we focus our attention on two mathematical models applied to two real situations, both studied with the theory of variational inequalities. The first network-based model describes the organ transplant system with the aim of minimizing the total costs associated with this process. We find the related optimality conditions and the variational inequality formulation. Some existence and uniqueness results as well as the Lagrange formulation are stated and some numerical examples are studied. The second mathematical model presented is a Generalized Nash Equilibrium model for postdisaster
humanitarian relief. We identify the network structure of the problem, with logistical and financial ows, and propose a variational equilibrium framework, which allows us to then formulate, analyze, and solve the model using the theory of variational inequalities. We then utilize Lagrange analysis and finally we illustrate the game theory model through a case study
Hybrid System of Systems Control : the TOKAMAK scenario
No full textThe basic definition of System-of-Systems (SoS) is that of a large-scale
integration of many independent, self-contained systems having the
common aim of satisfying a global need. Under this perspective, lots of
systems of systems can be found in several fields where a common final
goal drives systems towards a final SoS state. In nuclear fusion research
area, several examples of SoS applications can be made. From the integration
of all the constituents of the TOKAMAK machines which work
together to achieve a sustained nuclear fusion reaction, to the circuits
made of active analogue components mimicking plasma behavior, to
the neural networks made of connected units working together in order
to predict plasma variables behavior. In this work, investigation of
several SoS relevant in TOKAMAK scenario is performed and interesting
results enhancing the plant capabilities provided. This thesis itself
has been structured with a SoS-like structures where the integration of
self-contained chapters is performed in order to satisfy the global goal
that is improving TOKAMAK performances
Nanocarriers for nose-to-brain delivery: a novel strategy for the treatment of CNS disorders
No full textThe number of neurodegenerative diseases is estimated to be a few hundred. Despite the high prevalence and incidence, central nervous system (CNS) disorders are still incurable.
The blood-brain-barrier (BBB) precludes the delivery of drugs to the brain, preventing the therapy of a number of neurological disorders. In the last 20 years, intranasal (IN) administration has gained great attention in research and has been investigated with regard to its feasibility to serve as a direct drug transport route to the CNS. Drugs can be transported directly from the nasal cavity to the brain through the olfactory epithelium by trigeminal nerve systems and olfactory nerve pathways thereby bypassing the BBB. The incorporation of drugs into nanoparticles (NPs) might be a promising approach to improve the amount of pharmaceuticals delivered to the CNS. The goal of my PhD thesis is to assess the effective molecule delivery to the brain by using a new approach: IN administration combined with the nanotechnology-based carriers. My aim was to investigate whether polymeric NPs can end up the brain after IN administration; which region of the brain can be reached; how does surface property affect NPs transport. Once NPs translocation to the brain via this route was determined, our nanosystems have been formulated to study their potential application in epilepsy and brain cancer. We investigate PLGA NPs, unmodified and surface modified by PEG and chitosan. In Paper I we studied PEGylated PLGA NPs to obtain nanosystems with simple composition and long-term storage suitable for nose-to-brain delivery. A screening to select the degree of PEGylation of PLGA was performed and the effects of sucrose as surfactant-like and cryoprotectant agent was evaluated. Mucoadhesive evaluations between NPs and mucin were assessed by the mucin particle method and differential scanning calorimetry. Our results suggest the use of sucrose for its double effect and PEG 5% to confer an uncharged hydrophilic surface to minimize mucin-NPs adhesive interactions. Our nanosystems did not show any cytotoxic effects. In Paper II we looked at the in vivo fate of PLGA NPs and PLGA NPs surface modified with chitosan after IN administration in rats. The formulations have been optimized in terms of mean size and stability and tested in vivo. Both NPs were loaded with Rhodamine B and in vitro release study was evaluated by dyalisis bag technique. Biodistribution studies were carried out in rats after IN administration of NPs at different time intervals. Fluorescent microscopy was conducted to value the localization of NPs in the CNS. Our results suggest that compounds encapsulated in NPs may have a direct access to the CNS following IN administration. Our findings led us to hypothesize that different pathways were involved in the transport of unmodified and modified NPs. Additional experiments, were reported to confirm our results. In particular, the investigation of DiR-loaded PLGA NPs biodistribution and bioavailability to the brain after IN administration in living mice by Fluorescence Molecular Tomography system. Once established that our NPs reach the brain, we aim to investigate whether NPs can enhance the efficacy of the drugs loaded. Oxcarbazepine was encapsulated in PLGA NPs aiming at direct nose-to-brain delivery to improve epileptic therapy, and to evaluate the possible neuroprotection of this drug against the seizures and brain damage induced by Pentylentetrazole. Nose-to-brain delivery and NPs were also studied for gene therapy. We investigate the use of homemade polymers as potential delivery carriers of siRNA. The polymer bind to siRNA through electrostatic interaction to form nanocomplexes that were characterized in terms of size, zeta potential and stability. Cell cytotoxicity of the nanocomplex was determined in A431 cell line. Transfection and silencing efficiency were evaluated in vitro and in vivo after IN administration in rats by using Western Blot