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.

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.

Les manuscrits latins de la Chirurgia d'Albucasis et la lexicographie du latin m?di?val

Trotter, David, 'Les manuscrits latins de la Chirurgia d'Albucasis et la lexicographie du latin m?di?val', Archivum Latinitatis Medii Aevi (Bulletin Du Cange) (2001) 59(1) pp.181-202 RAE2008

Towards Eco-Dharma: The Contribution of Gandhian Thought to Ecological Ethics in India

Ecological concern prompts poor and indigenous people of India to consider how a society can ensure both protection of nature and their rightful claim for a just and sustainable future. Previous discussions defended the environment while ignoring the struggles of the poor for sustenance and their religious traditions and ethical values. Mohandas Karamchand Gandhi addressed similar socio-ecological concerns by adopting and adapting traditional religious and ethical notions to develop strategies for constructive, engaged resistance. The dissertation research and analysis verifies the continued relevance of the Gandhian understanding of dharma (ethics) in contemporary India as a basis for developing eco-dharma (eco-ethics) to link closely development, ecology, and religious values. The method of this study is interpretive, analytical, and critical. Françoise Houtart’s social analytical method is used to make visible and to suggest how to overcome social tensions from the perspective of marginalized and exploited peoples in India. The Indian government's development initiatives create a nexus between the eco-crisis and economic injustice, and communities’ responses. The Chipko movement seeks to protect the Himalayan forests from commercial logging. The Narmada Bachao Andolan strives to preserve the Narmada River and its forests and communities, where dam construction causes displacement. The use of Gandhian approaches by these movements provides a framework for integrating ecological concerns with people's struggles for survival. For Gandhi, dharma is a harmony of satya (truth), ahimsa (nonviolence), and sarvodaya (welfare of all). Eco-dharma is an integral, communitarian, and ecologically sensitive ethical paradigm. The study demonstrates that the Gandhian notion of dharma, implemented through nonviolent satyagraha (firmness in promoting truth), can direct community action that promotes responsible economic structures and the well-being of the biotic community and the environment. Eco-dharma calls for solidarity, constructive resistance, and ecologically and economically viable communities. The dissertation recommends that for a sustainable future, India must combine indigenous, appropriate, and small- or medium-scale industries as an alternative model of development in order to help reduce systemic poverty while enhancing ecological well-being.

Comparison of deterministic, stochastic and fuzzy logic uncertainty modelling for capacity extension projects of DI/WFI pharmaceutical plant utilities with variable/dynamic demand

The last 30 years have seen Fuzzy Logic (FL) emerging as a method either complementing or challenging stochastic methods as the traditional method of modelling uncertainty. But the circumstances under which FL or stochastic methods should be used are shrouded in disagreement, because the areas of application of statistical and FL methods are overlapping with differences in opinion as to when which method should be used. Lacking are practically relevant case studies comparing these two methods. This work compares stochastic and FL methods for the assessment of spare capacity on the example of pharmaceutical high purity water (HPW) utility systems. The goal of this study was to find the most appropriate method modelling uncertainty in industrial scale HPW systems. The results provide evidence which suggests that stochastic methods are superior to the methods of FL in simulating uncertainty in chemical plant utilities including HPW systems in typical cases whereby extreme events, for example peaks in demand, or day-to-day variation rather than average values are of interest. The average production output or other statistical measures may, for instance, be of interest in the assessment of workshops. Furthermore the results indicate that the stochastic model should be used only if found necessary by a deterministic simulation. Consequently, this thesis concludes that either deterministic or stochastic methods should be used to simulate uncertainty in chemical plant utility systems and by extension some process system because extreme events or the modelling of day-to-day variation are important in capacity extension projects. Other reasons supporting the suggestion that stochastic HPW models are preferred to FL HPW models include: 1. The computer code for stochastic models is typically less complex than a FL models, thus reducing code maintenance and validation issues. 2. In many respects FL models are similar to deterministic models. Thus the need for a FL model over a deterministic model is questionable in the case of industrial scale HPW systems as presented here (as well as other similar systems) since the latter requires simpler models. 3. A FL model may be difficult to "sell" to an end-user as its results represent "approximate reasoning" a definition of which is, however, lacking. 4. Stochastic models may be applied with some relatively minor modifications on other systems, whereas FL models may not. For instance, the stochastic HPW system could be used to model municipal drinking water systems, whereas the FL HPW model should or could not be used on such systems. This is because the FL and stochastic model philosophies of a HPW system are fundamentally different. The stochastic model sees schedule and volume uncertainties as random phenomena described by statistical distributions based on either estimated or historical data. The FL model, on the other hand, simulates schedule uncertainties based on estimated operator behaviour e.g. tiredness of the operators and their working schedule. But in a municipal drinking water distribution system the notion of "operator" breaks down. 5. Stochastic methods can account for uncertainties that are difficult to model with FL. The FL HPW system model does not account for dispensed volume uncertainty, as there appears to be no reasonable method to account for it with FL whereas the stochastic model includes volume uncertainty.

L’isola delle madri assenti: tracce di presenza femminile nella narrativa storica siciliana contemporanea (1990-2007)

The watershed constituted by the historical novels of Leonardo Sciascia (1921- 1989), Vincenzo Consolo (1933-2012) and Andrea Camilleri (born 1925), are starting points for analysing subsequent writings of history in Sicily, particularly those that deal with the hermeneutical function of literature as a means of critically reading official historiography. Nevertheless, whereas ample critical attention has been paid to male writers, whose work is deemed ‘mainstream’, there has been insufficient analysis of the role of female authors in relation to literary representations of Sicilian history. By considering the distinctiveness of the Sicilian literary tradition, the thesis identifies a series of transformations of the genre which have occurred in recent years within the context of feminine writing, and examines the historical narratives of contemporary Sicilian writers Maria Attanasio, Silvana La Spina and Maria Rosa Cutrufelli produced between 1990 and 2007. The study problematizes the lack of critical debate about feminine narratives in Sicily, and places these works in relation to developments in gender and genre theory, focusing particularly on Margherita Ganeri’s studies on the historical genre and the canon. After an introductory chapter which argues the case for examining Sicilian female historical fiction as a distinct literary practice, the subsequent chapters feature textual analyses of each author’s main historical fiction works, supporting the reading of the texts with theoretical readings, including the micro-history of Carlo Ginzburg, the écriture féminine of Hélène Cixous, the abjection theory of Julia Kristeva, the theoretical propositions on “experience” by Joan Wallach Scott and Teresa De Lauretis, and the theory of gender as performance proposed by Judith Butler. The analyses underline the importance of the authors’ distinct feminine perspective over Sicilian history and ultimately suggest that the three writers represent significant examples of a “nomadic writing” to be placed outside the Sicilian male literary tradition.

Nuove intersezioni: crimine e storia nella narrativa Italiana al cambio di millennio

My research investigates a recent tendency in Italian literature, characterized by elements of renewal within the novel-writing tradition and of discontinuity with postmodern culture. It proposes an interpretation of the genres of the historical novel and crime fiction in the last fifteen years, in order to underline the important role played by these types of narrative in revitalizing contemporary Italian literature. These modalities of writing are considered both individually and in their connections beyond a traditional notion of genre, emphasizing those characteristics which may be assumed as irreconcilable with a postmodern approach to fiction and those which, furthermore, seem to indicate attempts to take a new course. In particular, my study analyses the recent literary tendency to combine the elements of ‘crime’ and ‘history’ in order to represent political and social reality, and how the works examined relate to postmodern narrative. For this reason, I pay particular attention to the relationship between literature and the past and to the socio-political aspects connected with the praxis of narrating, offering an original interpretation of the way in which the authors studied engage with these characteristics.

Eco-evolutionary trophic dynamics: loss of top predators drives trophic evolution and ecology of prey.

Ecosystems are being altered on a global scale by the extirpation of top predators. The ecological effects of predator removal have been investigated widely; however, predator removal can also change natural selection acting on prey, resulting in contemporary evolution. Here we tested the role of predator removal on the contemporary evolution of trophic traits in prey. We utilized a historical introduction experiment where Trinidadian guppies (Poecilia reticulata) were relocated from a site with predatory fishes to a site lacking predators. To assess the trophic consequences of predator release, we linked individual morphology (cranial, jaw, and body) to foraging performance. Our results show that predator release caused an increase in guppy density and a "sharpening" of guppy trophic traits, which enhanced food consumption rates. Predator release appears to have shifted natural selection away from predator escape ability and towards resource acquisition ability. Related diet and mesocosm studies suggest that this shift enhances the impact of guppies on lower trophic levels in a fashion nuanced by the omnivorous feeding ecology of the species. We conclude that extirpation of top predators may commonly select for enhanced feeding performance in prey, with important cascading consequences for communities and ecosystems.

Eco-evolutionary feedbacks in community and ecosystem ecology: interactions between the ecological theatre and the evolutionary play.

Interactions between natural selection and environmental change are well recognized and sit at the core of ecology and evolutionary biology. Reciprocal interactions between ecology and evolution, eco-evolutionary feedbacks, are less well studied, even though they may be critical for understanding the evolution of biological diversity, the structure of communities and the function of ecosystems. Eco-evolutionary feedbacks require that populations alter their environment (niche construction) and that those changes in the environment feed back to influence the subsequent evolution of the population. There is strong evidence that organisms influence their environment through predation, nutrient excretion and habitat modification, and that populations evolve in response to changes in their environment at time-scales congruent with ecological change (contemporary evolution). Here, we outline how the niche construction and contemporary evolution interact to alter the direction of evolution and the structure and function of communities and ecosystems. We then present five empirical systems that highlight important characteristics of eco-evolutionary feedbacks: rotifer-algae chemostats; alewife-zooplankton interactions in lakes; guppy life-history evolution and nutrient cycling in streams; avian seed predators and plants; and tree leaf chemistry and soil processes. The alewife-zooplankton system provides the most complete evidence for eco-evolutionary feedbacks, but other systems highlight the potential for eco-evolutionary feedbacks in a wide variety of natural systems.

Eco-evolutionary dynamics: intertwining ecological and evolutionary processes in contemporary time.

Evolution occurring over contemporary time scales can have important effects on populations, communities, and ecosystems. Recent studies show that the magnitude of these effects can be large and can generate feedbacks that further shape evolution.