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I fenomeni di Debris Flows dell'Appennino Umbro-Marchigiano (versante Adriatico): caratterizzazione geomorfologico-idraulica, analisi della pericolosita' e GIS
La tesi [...] ha per argomento l’analisi geomorfologica ed idraulica dei fenomeni di debris flows che caratterizzano il versante adriatico della dorsale dei monti Sibillini (Appennino centrale), ed e' stata effettuata attraverso l’applicazione di diverse metodologie di lavoro, partendo da un rilevamento geomorfologico di campagna dei fenomeni di debris flows che hanno caratterizzato e caratterizzano tale area. L’analisi e' stata poi condotta attraverso studi di dettaglio, corredati da monitoraggi effettuati sulle aree ove la ricerca storica e bibliografica ed i rilevamenti di campagna hanno evidenziano una maggiore propensione all’attivazione di fenomeni di trasporti di massa, soprattutto in corrispondenza della presenza di strutture ed infrastrutture antropiche. Sono state quindi dettagliatamente investigate le modalita' di sviluppo e la reologia dei movimenti ed e' stata elaborata una banca dati sui processi e sulle condizioni al contorno. Pertanto il lavoro e' stato svolto dapprima a piccola scala attraverso il censimento dei fenomeni legati al “trasporto di massa” presenti nell’area di studio, ognuno dei quali e' stato approfondito –a scala più grande- attraverso un approccio metodologico consequenziale e per steeps: indagini storiche e d’archivio, rilievo geomorfologico di dettaglio, ricostruzione – ove possibile - dell’evoluzione del paesaggio anche in rapporto all’antropizzazione del territorio, analisi morfometriche ed idrauliche sui bacini montani sede dei processi di trasporto di massa, analisi sedimentologiche sui materiali coinvolti, stime volumetriche dei materiali amovibili ed elaborazione di cartografie, sezioni e schede informatizzate per la realizzazione di una banca dati continuamente aggiornabile. Analogamente sono state effettuate analisi spazio-temporali delle caratteristiche meteo-climatiche delle area di studio in modo da avere una precisa caratterizzazione termo-pluviometrica delle aree ove tali fenomeni di trasporto di massa si manifestano maggiormente: e' stato possibile quindi definire le condizioni favorevoli all’innesco di tali fenomeni in modo che plasmando il modello sull’intera scala di studio possano essere, successivamente, evidenziate le aree a maggior probabilita' di accadimento di fenomeni di trasporto di massa.\ud
La metodologia di studio utilizzata nel progetto di ricerca e' innovativa nel panorama scientifico, in quanto i fenomeni di debris flows sono sempre stati trattati da un punto di vista idraulico e meno da un punto di vista geologico-geomorfologico, tralasciando o non dando il giusto risalto a quelle caratteristiche geo-litologiche e morfologiche che invece molta importanza hanno nella comprensione dei meccanismi di innesco e nelle probabilita' che tali fenomeni si attivino
Transition metals in silicate glasses: the cases of zinc, hafnium and tantalum\ud
Many analytical and structural techniques, typically characteristic of the physical sciences, are more\ud
and more being used in materials science, biology and geology, to better understand structure, composition and other properties of compounds of different types, from organic to inorganic, from amorphous to crystalline, in all the different states of matter, solid or liquid or gas (for a review, see, p.e., .Hawthorne 1988 and Beran et Libowitzky 2004).\ud
The studies are mainly based on the use of spectroscopic methods which utilize a wide range of the electromagnetic spectrum (from microwaves to X-rays), but there is an extensive use of other techniques as well, like neutron spectroscopy or scattering and magnetic resonance to solve a\ud
variety of problems, examining different properties, on the basis of frequency (wavelength) and intensity of the signals. Composition, chemical and physical structure, electrochemical properties, are some of the information which can be obtained.\ud
In geology some of these techniques have been used already for a long time, others are new, with a faster and faster development and always new applications. Among them, most powerful are the techniques based on the use of X-rays, as very strong and tuneable X-ray radiation sources are\ud
available all around the world (mostly synchrotrons, but even Free Electron Laser facilities will be available for particular fast and powerful spectrometry) where spectra can be collected quickly and efficiently, together with less intense but more diffuse ones (X-ray tubes or even natural sources).\ud
X-rays also have a great flexibility: absorption and emission spectroscopy, diffraction, tomography can be applied and give very complete information on the same sample, respectively about composition, geometry and 3D structure, and can be performed sometime almost at the same time, using the suitable optics and detectors, thanks to the new synchrotron radiation facilities.\ud
For example, X-ray Absorption Spectroscopy (XAS) can be used to study different properties: chemistry, geometry, surface structure, and so on. Theory and experiments are growing together to get better results and to interpret them in an efficient and more coherent way. Nowadays the\ud
interpretation of spectra is much more standardized than in the past, many procedures are becoming routinely and several software products are available to extract physical and chemical data.\ud
However, the typical experiment to be performed on samples of geological relevance has its own intrinsic problems: samples can be very small, requiring the use of microbeams, or the element of interest is very light or very diluted, requiring special beamlines and experimental set-ups. In most cases these problems are summed together, since it is very common to have the need to analyse samples with at least two of the above mentioned characteristics. Moreover, the researcher has to deal sometimes with samples of complex chemical composition or is in the need of analysing\ud
samples at high temperature or high pressure or variable redox conditions, just to try to reproduce the environment where a sample (e.g., mineral or magma) can form. The use of XAS is able to solve many of the experimental problems relevant for the Earth sciences, certainly not all of them,\ud
and in the years it has been applied to a variety of compounds and topics.\ud
XAS is based on absorption cross section in X rays frequencies, strongly dependent on atomic species. The spectrum has an edge corresponding to typical frequencies (absorption edge, due to energy gap between energy of two electronic bound levels, or between a bound electron and\ud
continuum energy, that is when electron is no more bound to the atom), whose position is mainly, but not only, dependent on the atom, but also slightly on the surrounding environment.\ud
In fact, typical energies and spectrum features of an absorption spectrum vary not only depending on the chemical species of the absorber, but, even if the absorber is the same, there are some differences due to composition and structure, chemical and physical features which make the\ud
spectra useful to determine characteristics of the absorbing atom like the oxidation state, coordination geometry, bond distances, disorder, chemical environment. X-ray Absorption Near Edge Spectroscopy (XANES) and Extended X-ray Absorption Fine Structure (EXAFS) are respectively the name of spectroscopy techniques referring to the pre- and near edge part of the spectrum and the post-edge spectrum. They can give different but complementary information about geometry and chemistry of central atom (photoabsorber) and its neighbourhood.\ud
To extract structural information, powerful and complete theories about X-ray absorption have been developed since 1970s, and nowadays there are software programs suitable to give tools to compare data with theory in an efficient way.\ud
In this research we examined the results of XANES and EXAFS measurements carried out at the European Synchrotron Radiation Facility in Grenoble (F) on synthetic silicate glasses containing transition metals (in particular Zinc, Hafnium and Tantalum), following a research line already open in our research group. The study of these elements in a series of glasses of different bulk composition, reproducing the major rock types and magma compositions (from a granitic to basaltic), is aimed at determining the geochemical and structural role of three transition elements in these glasses, considered as synthetic analogue of different melt types. Zn is associated to the genesis of ore deposits, therefore it can be an abundant component but, in spite of this, its structural role in the melts has never been determined by direct methods. The structural data obtained in this work have been also compared with data concerning the physical properties (viscosity and density) already determined on the same set of samples which show the relationships between Zn, glass composition and these properties. In the XAS experiments the glass used are S-free compositions, in a first approximation, to study how Zn behaves in presence of Oxygen when Sulfur is absent. In a following study we will synthesize S-bearing samples to investigate the variations introduced by the adding of this chemical species.\ud
In analyzing Ta and Hf , using again a set of different glass composition, we approached a different type of problem, which is related to the use of samples with a very low concentration to simulate the amounts usually related to these elements in magmas. The results, based on the EXAFS\ud
refinements and the comparison with theory, are however satisfying and produced structural models of their geochemical role, to be compared with data on Nb and Zr, elements to whom they are usually related due to their geochemical affinity.\ud
The study of glasses to solve geochemical problems is particularly useful since they can be considered a good approximation of a melt. A lot of information can be extracted from their study to be extrapolated, with the necessary precautions, to the interpretation of their geochemical behaviour, the magmatic processes, the chemical partitioning, the crystallization processes. In some\ud
cases, the comparison between structural and physical properties can help in giving a structural interpretation of the only observed variation in properties, exploring their mutual relationship.\ud
Moreover, these elements and the glass compositions systems above mentioned are more and more used in important and frequent technological applications, so that each improvement in knowledge of their behaviour can be of great interest. During this study in fact, it has been found that most of the literature found on these topics are related to materials science and technologically relevant applications of glasses and transition elements. We are certain therefore that the results of this study, when published, will contribute not only to geologically relevant problems but also to a wider field of discipline, from physics to chemistry.\ud
The exposition of the arguments treated in this research is so divided:\ud
- in chapter 1: a brief description of the structure and properties of silicate melts and their importance in scientific or applied studies is reported. Details on the network models for amorphous structures are reported, considering geometric description, structural parameters\ud
and crystal chemistry. Glasses are the samples we have been dealing with, so their general characteristics have been studied and treated in more detail, describing correlations with the silicate melts. The behaviour of the analyzed elements in glasses/melts is our final aim, so some generalities about elements geochemical classification, mainly applied to trace elements, and how they behave in glasses is reported.\ud
- in chapter 2 we introduce the physical and computational framework we are moving in: spectroscopic methods applied to material sciences, some generalities about X-rays, XAS\ud
theory in general and EXAFS/XANES in detail. How is possible to convert theory in practice, modelling and approximating complete theory to have consistent and reasonable calculations, the experimental techniques and procedures and tools used to extract physical data from raw spectra. A brief description of computational tool used in this work (GNXAS) is then given, without deepening on technical and computational aspects, but considering the\ud
model which it is based on and a block scheme of data manipulation. Also very few elements about synchrotron radiation and X-rays measurement facilities and techniques are briefly given. In the last part of this chapter, application to geology, and particularly to glasses and melts are described, with a short history, a bibliography and references about the state of the art of the specific topics. Some generalities about how and why XAS can be\ud
applied to amorphous materials conclude the chapter.\ud
- in chapter 3 we give all the data concerning the Zn-bearing samples, together with the XAS procedures and results about Zinc in the glasses. We start with the literature data available on Zinc glasses and compounds, with details concerning the group of samples used as\ud
standard materials, and how XAS has been applied to understand microscopic structure.\ud
Finally the XAS spectra have been interpreted by building up theorethical models using clusters of different types and dimensions which have been compared to the experiments.\ud
- in chapter 4 and 5 the complete results and interpretation of data regarding respectively Hafnium and Tantalum, using the same procedure as Zinc, with particular emphasis on EXAFS analysis and the building of suitable clusters.\ud
- the conclusions, with a summary of the most important results obtained from the analysis of the glasses with the three elements studied.\ud
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Thermal properties of a homogeneous ultra-cold Fermi gas in the BCS-BEC crossover
In this thesis we evaluate the total energy E of a homogeneous ultra-cold Fermi gas with the approach developed by Prof. Strinati’s group at the University of\ud
Camerino. The obtained results are in good agreement both with the experimental data and with Quantum Monte Carlo simulations at zero temperature and in the so-called unitary limit (where the scattering length diverges). The behavior of E as a function of T appears to be non-monotonic, with negative specific heat and entropy in a region of temperatures near T = 0. At the unitary limit, the\ud
agreement with QMC calculations is quite good at zero temperature but worsens in the temperature region near the transition, where the energy and the chemical potential are smaller than expected. The results for strong coupling show the presence of a fluctuative contribution of the same order of the mean-field term, thereby preventing the recovering of the correct bosonic mean-field energy. This term appears to have been already described in the literature, where it was interpreted as leading to a renormalization of the bosonic scattering length.\ud
Successively, we have introduced corrections to the approach in order to improve the agreement with QMC simulations in the region of temperatures near the transition, and in general to improve the theory in the strong-coupling limit. This has been made with the inclusion of the Popov’s self-energy in the T-matrix. With this novel approach, we have evaluated the critical temperature and chemical potential of a gas of ultra-cold fermions in the BCS-BEC crossover. The obtained results show at unitarity a substantial reduction of the discrepancy with respect to recent Quantum Monte Carlo simulations for the critical temperature, and provide an upwards shift of more than 10% for the chemical potential with respect to the case where the Popov’s corrections are not included.\ud
These results show that the Popov’s corrections represent the most important part of the fluctuations which are needed to describe the BCS-BEC crossover in a detailed way.\u
Enhanced tumor radiosensitivity by the dual PI3K/mTOR inhibitor NVPBez235 in Non Small Cell Lung Cancer\ud
Non small cell lung cancer is the leading cause of death world-wide (Parkin, 2002). Lung cancer is often refractory to therapy due to the resistance to nonsurgical treatment modalities.\ud
Despite the tremendous advances that have occurred in the field of oncology during the last several years, the prognosis for this disease has remained dismal with an overall survival rate for newly diagnosed patients of about 5%. Novel and more effective therapeutic strategies are urgently needed for this devastating disease.\ud
We studied non-small cell lung cancer (NSCLC), the most prevalent form of this disease worldwide. About 30% of NSCLC is initiated by oncogenic K-Ras (onc-K-Ras). K-Ras controls signaling networks that are critical for cell survival and proliferation. K-Ras tumor associated\ud
mutations cause its constitutively activation and aberrant upregulation of downstream signaling pathways such as the RAF/MEK/ERK and phosphoinositide 3-kinase(PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling cascades.\ud
The events that lead to onc- K-Ras induced NSCLC are faithfully recapitulated in the mouse where expression of onc-K-Ras invariably leads to the development of adenomas and adenocarcinomas. It is of great interest that onc-K-Ras induced NSCLC completely regresses due to apoptosis when onc-K-Ras expression is experimentally shut off. These data were obtained in a transgenic mouse that expresses murine onc-K-Ras under the control of doxycycline (doxy) in\ud
bronchoepithelial stem cells (Tichelaar et al. 2000; Fisher et al. 2001). Previous studies have also demonstrated that the p110a subunit of PI3K is required to induce tumorigenesis in mice harboring K-Ras mutations.\ud
Treatment of lung cancer can involve a combination of surgery, chemotherapy, and radiation therapy. The sensitivity of cells to radiation induced death is a critical determinant of the probability of cure in patients receiving radiotherapy for cancer. Signaling events initiated by onc-K-Ras or PI3K converge to a common pathway which promotes tumor survival and resistance to apoptosis\ud
after radiation induced DNA damage (Gupta A. K., 2001). Moreover, inhibitors of the K-Ras and PI3K pathway are widely studied but clinical applicability in non small cell lung cancer is not yet shown.\ud
Since NSCLC is critically dependent on sustained expression of onc-K-Ras and its signalling pathway confers radiation resistance, our hypothesis is that effective inhibition of the onc-K-Ras signaling pathway in combination with radiation therapy would lead to a significant antitumor effect.\ud
In this study, we explored the antitumor effects of the inhibition of PI3K signaling pathway and its effects on radioresistance. We tested our hypothesis with Bez235, a specific PI3K/mTOR inhibitor already in the advanced phase of clinical development. We used human and mouse derived\ud
NSCLC cell lines harboring K-Ras and PI3K mutations. In addition, we performed in vivo studies in a K-Ras doxycycline inducible mouse lung cancer model and with xenografts of human NSCLC cell lines. Importantly, we found that PI3K/mTOR inhibitors can function as potent radiosensitizers in human NSCLC cells. Our work provides the rationale for the development of novel therapies for\ud
NSCLC and other cancers induced by onc- K-Ras.\u
Online Public Service Delivery for Small and Medium sized Organizations
The introduction of online public services may be hold new opportunities for citizens and businesses creating new value in their everyday activities.\ud
A key element in guaranteeing equal opportunities for all is making these services better, more accessible, and more cost-effective. Due to limited resources, Small and Medium sized Public Organizations are hampered in their efforts to provide suitable online services. In Italy, for instance, there are six thousands municipalities that cover a specific geographic region serving less than five thousands citizens usually located in rural or isolated area. These\ud
small authorities risk to be out from the actuation of many innovative programs for (at least) three main reasons: (i) the impossibility to get proper funds for the realization of innovative processes, (ii) the lack of adequate skills to support innovation and (iii) the lack of proper technological infrastructures.\ud
The primary aim of this research is to support Small and Medium sized Public Organizations in confronting these demanding challenges concerning their ability to provide next generation of online public services. In particular, we introduce a Shared Services environment to achieve operational efficiency among public organizations in a cost-effective way. A Shared Services environment is a collaborative strategy in which a subset of existing\ud
functions are concentrated into a new, semi-autonomous organizational unit that has a management structure designed to promote efficiency, value generation, cost savings, and improved service for the internal groups of the involved organizations. Our work uses the concept of Shared Services to share administrative processes among Small and Medium Sized Organizations. In this way, each organization can focus on its core activities and improve organisational competences. The result is the delivering of more citizen and business-centric services.\ud
In this work, each single organization separates the operational processes from the administrative ones that are instead shared among different organizations reducing duplicate efforts. This allows organizations to develop their strategic functions while optimizing investments by sharing services and resources of common interest. These services are concentrated and supplied by means of a modular architecture based on reusable building blocks. Our contribution is currently under experimentation and involves around the eighty per cent of rural authorities of Le Marche region (in the middle of Italy). The regional authority, Regione Marche, has a coordination role because it has the authority to manage the cooperation among underlying authorities (such as municipal districts). It is also able to plan and detect proper strategies within its territory
Biotechnological approach to obtain an efficient\ud expression of a new dualistic receptor recently\ud deorphanized: GPR17
G-protein coupled receptors (GPCRs) are the largest family of receptor proteins in mammals and play important roles in many physiological and pathological processes including allergies, cardiovascular dysfunction, depression, obesity, cancer, pain, diabetes, and a variety of central nervous system disorders, and represent the most common target of drugs.\ud
The progress of human genome sequencing has revealed the existence of several hundred orphans GPCRs, whose deorphanization and identification is essential in\ud
order to clarify their physio-pathological role and identify new drug targets. Recently, an orphan GPCR receptor phylogenetically and structurally related to known P2Y receptors has been identified. This receptor, namely GPR17, is a dual uracil nucleotides/cysteinyl-leukotrienes receptor, primarily expressed in the brain, and seems to play a key role in the progression of brain ischemic damage. This “dual” response is quite unusual, since all known G-protein-coupled receptors are activated by one single family of endogenous ligands. In order to design potent and specific agonists and antagonists for the GPR17 receptor, information about its structure, construction, and confirmation of the potential binding sites would be highly useful.\ud
Moreover, the availability of cell lines expressing human GPR17 (hGPR17) at high levels would be extremely useful for the functional characterization of the receptor and the screening of new potential anti-ischemic ligands.\ud
The first part of the research has been focused on the construction of a Flag tagged hGPR17 receptor. Flag tagged hGPR17 receptor vector construct has been expressed in COS-7 cells and identified by both immuno-cytochemistry assay and Western Blotting analysis. This expression vector is utilized to purify the target hGPR17 receptor protein by chromatography.\ud
In order to characterize this receptor, human astrocytoma 1321N1 has been chosen as the most appropriated cell line. In fact, this cell line expresses neither nucleotide\ud
(P2Y-like) receptors, nor CysLT receptors; therefore it is a useful tool to study the “dual” nature of the hGPR17. However, high levels of receptor expression are very\ud
difficult to obtain in these cells because they have a particular resistance to transfection. Therefore, different transfection methods, such as Calcium phosphate,\ud
Lipofectamine, Fugene, Arrest-InTM, Microporation, and Nucleofection have been used and expression of hGPR17 compared by quantitative real time PCR.\ud
The results showed different levels of transfection efficiency in the used techniques, with the Arrest-In lipo-polymeric formulation being the best method to promote an\ud
enriched hGPR17 gene delivery into human astrocytoma cell line.\ud
In the last part of the work, tagging EGFP-hGPR17, HIS-hGPR17 has been performed. Tagging of GPCRs with the enhanced green fluorescent protein (EGFP) and HIS peptide has enabled the direct visualization of real-time trafficking of GPCRs in living cells. Hence, EGFP-hGPR17 and HIS-hGPR17 gene constructs have been used to express tagged protein in different mammalian cells (1321N1, HEK-293, COS-7 cells), allowing to identify the hGPR17 protein subcellular localization.\ud
Moreover, since EGFP-hGPR17 and HIS-hGPR17 are comparable to the authentic protein and the possibility for the tag to affect normal folding of polypeptide chain during translation is minimized, these mammalian expression hGPR17 construct can be used to analyze protein-protein interaction by fluorescence resonance energy transfer (FRET) detection as well as by FLAG-hGPR17. This proteomic analysis strongly suggests that this data will be more supportive for further functional analysis of hGPR17, such as drug screening, protein-protein interaction, microarray analysis, which will lead to the discovery of hGPR17 implication in brain ischemia and related diseases, such as multiple sclerosis, Alzheimer, etc., This findings are promising and supportive, since are applicable to other orphan P2Y like receptors or to orphan GPCRs deorphanization
The former Sadam Property in Fano – Territorial Condensers and the Ability to Interfere/Dialogue with Networks
Interoperability in e-Government Services
Today, e-Government is an emergent multidisciplinary research field that has the aim to support the delivery of electronic information and services to citizens, businesses, and other stakeholders. This vision should be based on an effective cooperation between Public Administrations (PAs) that need to be more and more organized to delivery value-added e-Government services. Such cooperative environments should interconnect several PAs using interoperability architectures exploiting the service-oriented paradigm. \ud
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Service-orientation provides a general framework to enable interoperability allowing different systems to exchange data, participate in business processes, and cooperate to reach a common goal. Furthermore, a strong relationship between the e-Government high-level service concept and the more technological service concept used in Service Oriented Architectures has been found analysing current research. \ud
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In this thesis I propose some design guidelines for the engineering of service- oriented systems for the delivery of e-Government services. The role of metadata is discussed as a fundamental for the development of interoperability architectures inside the domain and a central role has given on documents production and description. Moreover, some approaches to testing and verification are showed to improve the development of the service-oriented backend of Public Administrations. \ud
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Although these approaches has been studied and developed in e-Government domain, some of them can be applied in generic service-oriented systems
Reproductive responses of Sarda ewe lambs treated for oestrus induction and synchronization during non-breeding season
This thesis is the result of studies concerning the reproductive responses of Sarda breed ewes undergo different techniques for induction and synchronization of oestrus during non-breeding season. A combination of\ud
pharmacological techniques (with use of progestagens plus gonadotrophins) and management techniques like the “male effect” was evaluated. Similar results in oestrus incidence and fertility were obtained after using intravaginal sponges\ud
containing 40 mg of fluorogestone acetate (FGA) for 9, 12 or 14 days. In this regard, similar results were obtained after using different doses of Pregnant Mare Serum Gonadotrophin (PMSG) injected at the moment of sponge\ud
withdrawal. A single administration of 35 mg of natural Progesterone (P4 priming) associated with PMSG did not seem to induce oestrus behaviour or affect the sexual activity and pregnancy rate of the ewe lambs during nonbreeding\ud
season. Similarly, also the “ram effect” did not seem to have any influence on the pregnancy rate and ovarian activity when used singly in ewe lambs. Considering early pregnancy diagnosis and ovarian activity evaluation,\ud
transrectal ultrasound method proved to be practicable in field conditions without previous fast or water restriction in Sarda ewe lambs. Considering adult, multiparous and lactating Sarda ewes, a single administration of 33 mg of\ud
natural Progesterone (P4 priming) plus PMSG before the introduction of the rams concentrated oestrus 17 to 22 days later and enhanced pregnancy rates