Il Sistema di Revenue Management strumento per lo sviluppo turistico sostenibile delle destinazioni

Businesses interact constantly with the environment, realizing several and heterogeneous exchanges. Organizations can be considered a system of different interests, frequently conflicting and the satisfaction of different stakeholders is a condition of success and survival. National and international literature attempts to explain the complex connection between companies and environment. In particular, the Stakeholder Theory considers crucial for businesses the identification of different stakeholders and their involvement in decision-making process. In this context, profit can not be considered the only purpose of companies existence and business aims become more numerous and different. The Stakeholder Theory is often utilized as framework for tourism studies, in particular in Sustainable Tourism Development research. In fact, authors consider sustainable the tourism development able to satisfy interests of different stakeholders, traditionally identified as local community and government, businesses, tourists and natural environment. Tourism businesses have to guarantee the optimal use of natural resources, the respect of socio-cultural tradition of local community and the creation of socio-economic benefits for all stakeholders in destinations. An obstacle to sustainable tourism development that characterizes a number of destinations worldwide is tourism demand seasonality. In fact, its negative impact on the environment, economy and communities may be highly significant. Pollution, difficulties in the use of public services, stress for residents, seasonal incomes, are all examples of the negative effects of seasonality. According to the World Tourism Organization (2004) the limitation of seasonality can favour the sustainability of tourism. Literature suggests private and public strategies to minimize the negative effects of tourism seasonality, as diversification of tourism products, identification of new market segments, launching events, application of public instruments like eco-taxes and use of differential pricing policies. Revenue Management is a managerial system based on differential pricing and able to affect price sensitive tourists. This research attempts to verify if Revenue Management, created to maximize profits in tourism companies, can also mitigate the seasonality of tourism demand, producing benefits for different stakeholders of destinations and contributing to Sustainable Tourism Development. In particular, the study attempts to answer the following research questions: 1) Can Revenue Management control the flow of tourist demand? 2) Can Revenue Management limit seasonality, producing benefits for different stakeholders of a destination? 3) Can Revenue Management favor the development of Sustainable Tourism? The literature review on Stakeholder Theory, Sustainable Tourism Development, tourism seasonality and Revenue Management forms the foundation of the research, based on a case study approach looking at a significant destination located in the Southern coast of Sardinia, Italy. A deductive methodology was applied and qualitative and quantitative methods were utilized. This study shows that Revenue Management has the potential to limit tourism seasonality, to mitigate negative impacts occurring from tourism activities, producing benefits for local community and to contribute to Sustainable Tourism Development.

Exploitation of Ebola Virus VP35 Protein to identify new drugs counteracting its type I IFN antagonism

Ebolaviruses (EBOVs) are among the most virulent and deadly pathogens ever known, causing fulminant haemorrhagic fevers in humans and non-human primates. The 2014 outbreak of Ebola virus disease (EVD) in West Africa has claimed more lives than all previous EVD outbreaks combined. The EBOV high mortality rates have been related to the virus-induced impairment of the host innate immunity reaction due to two virus-coded proteins, VP24 and VP35. EBOV VP35 is a multifunctional protein, it is essential for viral replication as a component of the viral RNA polymerase and it also participates in nucleocapsid assembly. Early during EBOV infection, alpha-beta interferon (IFN-α/β) production would be triggered upon recognition of viral dsRNA products by cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). However, this recognition is efficiently prevented by the double-stranded RNA (dsRNA) binding activity of the EBOV VP35 protein, which hides RLRs binding sites on the dsRNA phosphate backbone as well the 5’-triphosphate (5’-ppp) dsRNA ends to RIG-I recognition. In addition to dsRNA binding and sequestration, EBOV VP35 inhibits IFN-α/β production preventing the activation of the IFN regulatory factor 3 (IRF-3) by direct interaction with cellular proteins. Previous studies demonstrated that single amino acid changes in the VP35 dsRNA binding domain reduce EBOV virulence, indicating that VP35 is an attractive target for antiviral drugs development. Within this context, here we report the establishment of a novel method to characterize the EBOV VP35 inhibitory function of the dsRNA-dependent RIG-I-mediated IFN-β signaling pathway in a BLS2 cell culture setting. In such system, a plasmid containing the promoter region of IFN-β gene linked with a luciferase reporter gene was transfected, together with a EBOV VP35 mammalian expression plasmid, into the IFN-sensitive A549 cell line, and the IFN-induction was stimulated through dsRNA transfection. Through alanine scanning mutational studies with biochemical, cellular and computational methods we highlighted the importance of some VP35 residues involved in dsRNA end-capping binding, such as R312, K282 and R322, that may serve as target for the development of small-molecule inhibitors against EBOV. Furthermore, we identified a synthetic compound that increased IFN-induction only under antiviral response stimulation and subverted VP35 inhibition, proving to be very attractive for the development of an antiviral drug. In conclusion, our results provide the establishment of a new assay as a straightforward tool for the screening of antiviral compounds that target i) dsRNA-VP35 or cellular protein-VP35 interaction and ii) dsRNA-dependent RIG-I-mediated IFN signaling pathway, in order to potentiate the IFN response against VP35 inhibition, setting the bases for further drug development.

Progettazione e sintesi di nuovi antagonisti CB1 a struttura pirazolica come potenziali radiofarmaci per la PET imaging

Cannabinoid receptors are members of the large family of G-protein coupled receptors. Two types of cannabinoid receptor have been discovered: CB1 and CB2. CB1 receptors are localised predominantly in the brain whereas CB2 receptors are more abundant in peripheral nervous system cells. CB1 receptors have been related with a number of disorders, including depression, anxiety, stress, schizophrenia, chronic pain and obesity. For this reason, several cannabinoid ligands were developed as drug candidates. Among these ligands, a prominent position is occupied by SR141716 (Rimonabant), which is a pyrazole derivative with inverse agonist activity discovered by Sanofi-Synthelabo in 1994. This compound was marketed in Europe as an anti-obesity drug, but subsequently withdrawn due to its side-effects. Since the relationship between the CB1 receptors’ functional modification, density and distribution, and the beginning of a pathological state is still not well understood, the development of radio-ligands suitable for in vivo PET (Positron Emission Tomography) functional imaging of CB1 receptors remains an important area of research in medicine and drug development. To date, a few radiotracers have been synthesised and tested in vivo, but most of them afforded unsatisfactory brain imaging results. A handful of radiolabelled CB1 PET ligands have also been submitted to clinical trials in humans. In this PhD Thesis the design, synthesis and characterization of three new classes of potential high-affinity CB1 ligands as candidate PET tracers is described.

Caratterizzazione proteomica di fluidi e tessuti in diverse condizioni fisio-patologiche

This thesis has been focused on the proteomic characterization of human saliva from donors of different ages, starting from birth up to adult age, and pediatric brain tumor tissues. The first study has been performed in order to compare the acid-insoluble fraction of saliva from preterm with at-term newborns and adults and establish if differences exist. In the second study medulloblastoma and pilocytic astrocytoma pediatric brain tumor extracts have been compared. In both studies 2- DE analysis was coupled with high resolution tandem mass spectrometry (MS/MS). The proteomic characterization of the acid-insoluble fractions of saliva from preterm newborns allowed to integrate data previously obtained on the acid-soluble fraction by HPLC-electrospray ionization (ESI)-mass spectrometry (MS), and to evidence several differences between preterm newborns, at-term newborns and adults. Spots differentially expressed between the three groups, according to image analysis of the gels, were submitted to in-gel tryptic digestion and the peptide mixture analyzed by high performance HPLC-ESI-MS/MS for their characterization. By this strategy, we identified three over-expressed proteins in atterm newborns with respect to preterm newborns and adults (BPI fold-containing family A member 1, two proteoforms of annexin A1, and keratin type 1 cytoskeletal 13), and several over-expressed proteins in adults (fatty acid-binding protein, S100A6, S100A7, two proteoforms of S100A9, several proteoforms of prolactin-inducible protein, Ig kappa chain, two proteoforms of cystatin SN, one proteoform of cystatin S and several proteoforms of α-amylase 1). Moreover, for the first time, it was possible to assign by MS/MS four spots of human saliva 2-DE, already detected by other authors, to different proteoforms of S100A9. The strategy applied used a sequential staining protocol to the 2-DE gels, first with Pro-Q Diamond, that allows specific detection of phosphoproteins, and successively with total protein SYPRO Ruby stain. In the second study, proteomic analysis of two pediatric brain tumor tissues pointed out differences between medulloblastoma, the prevalent malignant tumor in childhood, and pilocytic astrocytoma, the most common, that only rarely shows a malignant progression. Due to the limited availability of bioptic tissue, the study was performed on pooled tumor tissues, and was focused on acid-insoluble fraction to integrate the characterization performed by a group of colleagues in Rome on the acid-soluble fraction by high performance HPLC-ESI-MS/MS. The results indicated that the two tumors exhibit different proteomic profiles and evidenced interesting differential expression of several proteins. Among them, peroxiredoxin- 1, peptidyl-prolyl cis–trans isomerase A, heterogeneous nuclear ribonucleoproteins A2/B1, mitochondrial isoform of malate dehydrogenase, nucleoside diphosphate kinase A, glutathione S-transferase P and fructose bisphosphate aldolase A resulted significantly over-expressed in medulloblastoma while glial fibrillary acidic protein, serotransferrin, α crystallin B chain, ferritin light chain, annexin A5, fatty acid-binding protein (brain), sorcin and apolipoprotein A-I resulted significantly over-expressed in pilocytic astrocytoma. In conclusion, the work done allowed to evidence the usefulness of using an integrated bottom-up/top-down approach, based on 2-DE-MS analysis and high performance MS in order to obtain a complete characterization of the proteome under investigation, revealing and identifying, not only peptides and small proteins, but also proteins with higher MW, that often it is not possible to identify by using exclusively a top-down ESI-MS approach.

Sopravvenienze e rimedi nel contratto d'appalto: la previsione del cosiddetto obbligo di rinegoziazione

In this thesis I study how the legal system reacts (or ought to react) to unforeseen circumstances that interfere with the functioning of long term contractual relationships. More precisely, I investigate whether mandatory renegotiation would be an appropriate tool to guarantee the flexibility that long-term relationships require. Furthermore, after having analyzed the instruments that our legal system offers to preserve long-term contractual relationships, I explore the solutions adopted by other legal systems. This comparative analysis helps to formulate normative proposals to improve the functioning of our legal system.

Risorse intangibili e imprese familiari: principali contributi sul tema e nuove prospettive di ricerca

Intangible resources are the distinctive factors for the success of businesses (Barney, 1991) and for this reason the literature has paid particular attention to this issue (Barney, 1991; Hall, 1992,1993; Carmeli, 2004; Galbreath, 2005; Hayton, 2005; Norman, Butler, Ranft, 2013). With this thesis I will analyze existing studies on the subject with particular reference to family businesses - ideal forum for the spread of specific intangibles (Ward, 1988; Habbershon, Williams, 1999; Sirmon & Hitt, 2003; Huybrechts et al., 2011; Rose, Howorth & Discua Cruz, 2014), in order to identify the main areas of research and new research perspectives. Through a narrative review on the general theme of intangible resources, bibliometric analysis of the contributions that jointly address the intangibles and family businesses and co-citation analysis for the definition of the intellectual structure of the studies on the intangible resources in family firms is reached an in-depth study of the issue with relevant academic and practical implications.

Una testimonianza silenziosa.Storia della Chiesa cattolica in Tunisia dal Trattato del Bardo alla ‘rivoluzione dei gelsomini’

The work examines the change involving the Church in Tunisia from the period of the Protectorate to the present through the fundamental moments of independence (1956) and the signing of the ‘Modus vivendi’ (1964). In the first structure of the “modern” Church, a fundamental role was played by the complex figure of the French Cardinal Charles-Allemand Lavigerie who, while giving strong impulse to setting up disinterested charitable social initiatives by the congregations (Pères Blancs, Soeurs Blanches and others), also represented the ideal of the ‘evangelizing’ (as well as colonial) Church which, despite its declared will to avoid proselytism, almost inevitably tended to slip into it. During the French Protectorate (1881-1956) the ecclesiastic institution concentrated strongly on itself, with little heed for the sensitivity of its host population, and developed its activities as if it were in a European country. From the social standpoint, the Church was mostly involved in teaching, which followed the French model, and health facilities. In the Church only the Pères Blancs missionaries were sincerely committed to promoting awareness of the local context and dialogue with the Muslims. The Catholic clergy in the country linked its religious activity close to the policy of the Protectorate, in the hope of succeeding in returning to the ancient “greatness of the African Church”, as the Eucharistic Congress in Carthage in 1930 made quite clear. The Congress itself planted the first seed in the twentyfive- year struggle that led the Tunisian population to independence in 1956 and the founding of the Republic in 1957. The conquest of independence and the ‘Modus vivendi’ marked a profound change in the situation and led to an inversion of roles: the Catholic community was given the right to exist only on the condition that it should not interfere in Tunisian society. The political project of Bourguiba, who led the Republic from 1957 to 1987, aimed to create a strongly egalitarian society, with a separation between political and religious powers. In particular, in referring to the Church, he appeared as a secularist with no hostility towards the Catholics who were, however, considered as “cooperators”, welcome so long as they were willing to place their skills at the service of the construction of the state. So, in the catholic Community was a tension between the will of being on the side of the country and that of conserving a certain distance from it and not being an integral part of it. In this process of reflection, the role of the Second Vatican Council was fundamental: it spread the idea of a Church open to the world and the other religions, in particular to Islam: the teaching of the Council led the congregations present in the country to accept the new condition. This new Church that emerged from the Council saw some important events in the process of “living together”, of “cultural mixing” and the search for a common ground between different realities. The almost contemporary arrival of Arab bishops raised awareness among the Tunisians of the existence of Christian Arabs and, at the same time, the Catholic community began considering their faith in a different way. In the last twenty years the situation has continued to change. Side by side with the priests present for decades or even those born there, some new congregations have begun to operate, albeit in small numbers: they have certainly revitalized the community of the faithful, but they sometimes appear more devoted to service “within” the Church, than to services for the population, and are thus characterized by exterior manifestations of their religion. This sort of presence has made it possible for Bourguiba's successor, Ben Ali (president from 1987 to 2011), to practice forms of tolerance even more clearly, but always limited to formal relations; the Tunisians are still far from having a real understanding of the Catholic reality, with certain exceptions connected to relations on a personal and not structured plane, as was the case in the previous period. The arrival of a good number of young people from sub-Saharan Africa, most of all students, belonging to the JCAT, and personnel of the BAD has “Africanized” the Church in Tunisia and has brought about an increase in Christians' exterior manifestations; but this is a visibility that is not blatant but discreet, with the implicit risk of the Church continuing to be perceived as a sort of exterior body, alien to the country; nor can we say, lacking proper documentation, how it will be possible to build a bridge between different cultures through the “accompaniment” of Christian wives of Tunisians. Today, the Church is living in a country that has less and less need of it; its presence, in the schools and in health facilities, is extremely reduced. And also in other sectors of social commitment, such as care for the disabled, the number of clergymen involved is quite small. The ‘revolution’ in 2011 and the later developments up to the present have brought about another socio-political change, characterized by a climate of greater freedom, but with as yet undefinable contours. This change in the political climate will inevitable have consequences in Tunisia’s approach to religious and cultural minorities, but it is far too soon to discuss this on the historical and scientific planes.

Caratterizzazione geo-petrografica, petrologica e geochimica di rocce anatettiche del nord Sardegna

The High Grade Metamorphic Complex (HGMC) of Variscan basement of north Sardinia is characterized by the widespread of migmatites. This study is focused on two localities of NE Sardinia (Porto Ottiolu and Punta Sirenella) where ortho- and para-derivates migmatites outcrop. A geological and structural survey was carried out, leading to the realization of a geological schematic map of Punta Sirenella area. Several samples of different rocks were collected for petrographic, micro-structural minero-chemical and geochemical analyses. In the Porto Ottiolu area three main deformation phases have been identified; D1, characterized by tight folds with sub-horizontal axes, rarely preserved in paragneisses; D2, that produce a pervasive foliation oriented N100° 45°SW marked by biotite and sillimanite blastesis and locally transposed by shear zone oriented N170°; D3, late deformation phase caused symmetric folds with sub-horizontal axes with no axial plane schistosity. Leucosomes form pods and layers along S2 schistosity but also leucosomes along shear zones have been observed. In the Punta Sirenella area, three main deformation phases have been identified; D1, is manifested by the transposition of centimeter-sized leucosomes and is rarely observed in paragneisses were produce open folds with sub-vertical axes; D2, NW-SE oriented on whose XY plane three mineralogical lineation (quartz+plagioclase, fibrolite+quarz and muscovite) lie; D3, a ductile-brittle deformation phase that produce a mylonitc S3 foliation that locally become the most evident schistosity in the field oriented N140° steeply dipping toward NE. In both areas, leucosomes of sedimentary-derived migmatites are generally trondhjemitic pointing out for a H2O fluxed melting reaction, but also granitic leucosomes have been found, produced by muscovite dehydration melting. Leucosomes of migmatitic orthogneiss instead, have granitic compositions. Migmatization started early, during the compressional and crustal thickening (sin-D1, pre-D2) and was still active during exhumation stage. For each studied outcrop of migmatite pseudosections for the average mesosome composition have been calculated; these pseudosections have been used to model the P-T conditions of anatexis on the basis of the melt volume (%) of melt, Si/Al and Na/K molar ratios, modal content of garnet and Si content in metamorphic white mica. Further pseudosections have been calculated for the average composition of leucosomes in order to define the P-T conditions of the end of the crystallization through intersection of solidus curve and isopleths of Si content in white mica and/or XMg ratio in biotite. Thermodynamic modeling on ortho- and sedimentary-derived migmatites of Punta Sirenella yield P-T conditions of 1.1-1.3 GPa - 670-740°C for migmatitic event and 0.75-0.90 GPa - 660-730°C for the end of crystallization. These conditions are fit well with previous studies on adjacent rocks. Modeling of Porto Ottiolu ortho- and sedimentary-derived migmatites yield P-T conditions of 0.85-1.05 GPa - 690-730°C for migmatitic event and 0.35-0.55 GPa - 630-690°C strongly affected by re-equilibration during exhumation, expecially for crystallization conditions. Geochemical analyses of samples belonging to Porto Ottiolu and Punta Sirenella orthogneisses show a strong link with those of other orthogneisses outcropping in NE Sardinia (for instance, Lode-Mamone and Golfo Aranci) that are considered the intrusive counterparts of middle-Ordovician metavolcanics rocks outcropping in the Nappe Zone. Thus, the studied ortogneiss bodies, even lacking radiometric data, can be considered as belonging to the same magmatic cycle.