Thermochronologic and geodynamic evolution of the Pontides: Sakarya terrane (Karakaya Complex) and Istanbul terrane, Turkey.

An integrated array of analytical methods -including clay mineralogy, vitrinite reflectance, Raman spectroscopy on carbonaceous material, and apatite fission-track analysis- was employed to constrain the thermal and thermochronological evolution of selected portions of the Pontides of northern Turkey. (1) A multimethod investigation was applied for the first time to characterise the thermal history of the Karakaya Complex, a Permo-Triassic subduction-accretion complex cropping out throughout the Sakarya Zone. The results indicate two different thermal regimes: the Lower Karakaya Complex (Nilüfer Unit) -mostly made of metabasite and marble- suffered peak temperatures of 300-500°C (greenschist facies); the Upper Karakaya Complex (Hodul and the Orhanlar Units) –mostly made of greywacke and arkose- yielded heterogeneous peak temperatures (125-376°C), possibly the result of different degree of involvement of the units in the complex dynamic processes of the accretionary wedge. Contrary to common belief, the results of this study indicate that the entire Karakaya Complex suffered metamorphic conditions. Moreover, a good degree of correlation among the results of these methods demonstrate that Raman spectroscopy on carbonaceous material can be applied successfully to temperature ranges of 200-330°C, thus extending the application of this method from higher grade metamorphic contexts to lower grade metamorphic conditions. (2) Apatite fission-track analysis was applied to the Sakarya and the İstanbul Zones in order to constrain the exhumation history and timing of amalgamation of these two exotic terranes. AFT ages from the İstanbul and Sakarya terranes recorded three distinct episodes of exhumation related to the complex tectonic evolution of the Pontides. (i) Paleocene - early Eocene ages (62.3-50.3 Ma) reflect the closure of the İzmir-Ankara ocean and the ensuing collision between the Sakarya terrane and the Anatolide-Tauride Block. (ii) Late Eocene - earliest Oligocene (43.5-32.3 Ma) ages reflect renewed tectonic activity along the İzmir-Ankara. (iii) Late Oligocene- Early Miocene ages reflect the onset and development of the northern Aegean extension. The consistency of AFT ages, both north and south of the tectonic contact between the İstanbul and Sakarya terranes, suggest that such terranes were amalgamated in pre-Cenozoic times. (3) Fission-track analysis was also applied to rock samples from the Marmara region, in an attempt to constrain the inception and development of the North Anatolian Fault system in the region. The results agree with those from the central Pontides. The youngest AFT ages (Late Oligocene - early Miocene) were recorded in the western portion of the Marmara Sea region and reflect the onset and development of northern Aegean extension. Fission-track data from the eastern Marmara Sea region indicate rapid Early Eocene exhumation induced by the development of the İzmir-Ankara orogenic wedge. Thermochronological data along the trace of the Ganos Fault –a segment of the North Anatolian Fault system- indicate the presence of a tectonic discontinuity active by Late Oligocene time, i.e. well before the arrival of the North Anatolian Fault system in the area. The integration of thermochronologic data with preexisting structural data point to the existence of a system of major E-W-trending structural discontinuities active at least from the Late Oligocene. In the Early Pliocene, inception of the present-day North Anatolian Fault system in the Marmara region occurred by reactivation of these older tectonic structures. 


Ricerca sulle Caratteristiche di Filtrabilità della Birra e Ottimizzazione del Processo di Filtrazione

Il presente lavoro ha avuto lo scopo di identificare le caratteristiche di filtrabilità della birra attraverso lo svolgimento di prove tecnologiche di filtrazione in scala di laboratorio e su scala pilota, utilizzando diverse tipologie di sistemi filtranti e sperimentando diversi materiali di membrana. La fase preliminare della caratterizzazione della filtrabilità della birra è stata condotta presso i laboratori del Campden-BRI – The Brewing Research International, Inghilterra, mentre le prove tecnologiche su scala pilota si sono svolte presso il CERB – Centro di Eccellenza per la Ricerca sulla Birra. Le prove di filtrazione e le analisi sui campioni hanno permesso di verificare le performance delle diverse membrane utilizzate in risposta alla variazione dei principali parametri del processo di filtrazione tangenziale. Sono stati analizzati diversi parametri di qualità della birra filtrata attraverso il monitoraggio del processo e lo svolgimento di prove analitiche sul prodotto volte ad evidenziare gli effetti delle differenti tecnologie adottate. Per quanto riguarda le prove di laboratorio per la caratterizzazione della filtrabilità della birra, l’analisi della PCS (Photon Correlation Spectroscopy) è stata utilizzata per verificare l’influenza di diversi trattamenti enzimatici sulla efficienza del processo di filtrazione e la loro influenza sulla stabilità colloidale della birra filtrata. Dai risultati ottenuti è emerso che il PCS è un valido strumento per determinare la distribuzione in classi di diametro e il diametro medio effettivo delle particelle solide in sospensione nella birra e può essere utilizzato sia per predire la stabilità della birra filtrata, sia per monitorare il processo di filtrazione in tempo reale.

Variation in peach fruit susceptibility to Monilinia laxa and gene expression

Brown rot caused by Monilinia laxa and Monilinia fructigena is considered one of the most important diseases affecting Prunus species. Although some losses can result from the rotten fruits in the orchard, most of the damage is caused to fruits during the post-harvest phase. Several studies reported that brown rot incidence during fruit development highly varies; it was found that at a period corresponding to the the pit hardening stage, fruit susceptibility drastically decreases, to be quickly restored afterwards. However the molecular basis of this phenomenon is still not well understood. Furthermore, no difference in the rot incidence was found between wound and un-wound fruits, suggesting that resistance associated more to a specifc biochemical response of the fruit, rather than to a higher mechanical resistance. So far, the interaction Monilinia-peach was analyzed through chemical approaches. In this study, a bio-molecular approach was undertaken in order to reveal alteration in gene expression associated to the variation of susceptibility. In this thesis three different methods for gene expression analysis were used to analyze the alterations in gene expression occurring in peach fruits during the pit hardening stage, in a period encompassing the temporary change in Monilinia susceptibility: real time PCR, microarray and cDNA AFLP techniques. In 2005, peach fruits (cv.K2) were weekly harvested during a 19-week long-period, starting from the fourth week after full bloom, until full maturity. At each sampling time, three replicates of 5 fruits each were dipped in the M.laxa conidial suspension or in distilled water, as negative control. The fruits were maintained at room temperature for 3 hours; afterwards, they were peeled with a scalpel; the peel was immediately frozen in liquid nitrogen and transferred to -80 °C until use. The degree of susceptibility of peach fruit to the pathogen was determined on 3 replicates of 20 fruits each, as percentage of infected fruits, after one week at 20 °C. Real time PCR analysis was performed to study the variation in expression of those genes encoding for the enzymes of the phenylpropanoid pathway (phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), cinnamate 4-hydroxylase (C4H), leucoanthocyanidine reductase (LAR), hydroxycinnamoyl CoA quinate hydroxycinnamoyl transferase (HQT) and of the jasmonate pathway, such as lipoxygenase (LOX), both involved in the production of important defense compounds. Alteration in gene expression was monitored on fruit samples of a period encompassing the pit hardening stage and the corresponding temporary resistance to M.laxa infections, weekly, from the 6thto the 12th week after full bloom (AFB) inoculated with M. laxa or mock-inoculated. The data suggest a critical change in the expression level of the phenylpropanoid pathway from the 7th to the 8th week AFB; such change could be directly physiologically associated to the peach growth and it could indirectly determine the decrease of susceptibility of peach fruit to Monilinia rot during the subsequent weeks. To investigate on the transcriptome variation underneath the temporary loss of susceptibility of peach fruits to Monilinia rot, the microarray and the cDNA AFLP techniques were used. The samples harvested on the 8th week AFB (named S, for susceptible ones) and on the 12th week AFB (named R, for resistant ones) were compared, both inoculated or mock-inoculated. The microarray experiments were carried out at the University of Padua (Dept. of Environmental Agronomy and Crop Science), using the μPEACH1.0 microarray together with the suited protocols. The analysis showed that 30 genes (corresponding to the 0.6% of the total sequences (4806) contained in the μPeach1.0 microarray) were found up-regulated and 31 ( 0.6%) down regulated in RH vs. SH fruits. On the other hand, 20 genes (0.4%) were shown to be up-regulated and 13 (0.3%) down-regulated in the RI vs. SI fruit. No genes were found differentially expressed in the mock-inoculated resistant fruits (RH) vs. the inoculated resistant ones (RI). Among the up-regulated genes an ATP sulfurylase, an heat shock protein 70, the major allergen Pru P1, an harpin inducing protein and S-adenosylmethionine decarboxylase were found, conversely among the down-regulated ones, cinnamyl alcohol dehydrogenase, an histidine- containing phosphotransfer protein and the ferritin were found. The microarray experimental results and the data indirectly derived, were tested by Real Time PCR analysis. cDNA AFLP analysis was also performed on the same samples. 339 transcript derived fragments considered significant for Monilinia resistance, were selected, sequenced and classified. Genes potentially involved in cell rescue and defence were well represented (8%); several genes (12.1%) involved in the protein folding, post-transductional modification and genes (9.2%) involved in cellular transport were also found. A further 10.3% of genes were classified as involved in the metabolism of aminoacid, carbohydrate and fatty acid. On the other hand, genes involved in the protein synthesis (5.7%) and in signal transduction and communication (5.7%) were found. Among the most interesting genes found differentially expressed between susceptible and resistant fruits, genes encoding for pathogenesis related (PR) proteins were found. To investigate on the association of Monilinia resistance and PR biological function, the major allergen Pru P1 (GenBank accession AM493970) and its isoform (here named Pru P2), were expressed in heterologous system and in vitro assayed for their anti-microbial activity. The ribonuclease activity of the recombinant Pru P1 and Pru P2 proteins was assayed against peach total RNA. As the other PR10 proteins, they showed a ribonucleolytic activity, that could be important to contrast pathogen penetration. Moreover Pru P1 and Pru P2 recombinant proteins were checked for direct antimicrobial activity. No inhibitory effect of Pru P1 or Pru P2 was detected against the selected fungi.

Erosione e sollevamento nell'arco calabro-peloritano

The Calabrian-Peloritani arc represents key site to unravel evolution of surface processes on top of subducting lithosphere. During the Pleistocene, in fact the arc uplifted at rate of the order of about 1mm/yr, forming high-standing low-relief upland (figure 2). Our study is focused on the relationship between tectonic and land evolution in the Sila Massif, Messina strait and Peloritani Mts. Landforms reflect a competition between tectonic, climatic, and surficial processes. Many landscape evolution models that explore feedbacks between these competing processes, given steady forcing, predict a state of erosional equilibrium, where the rates of river incision and hillslope erosion balance rock uplift. It has been suggested that this may be the final constructive stage of orogenic systems. Assumptions of steady erosion and incision are used in the interpretation of exhumation and uplift rates from different geologic data, and in the formulation of fluvial incision and hillslope evolution models. In the Sila massif we carried out cosmogenic isotopes analysis on 24 samples of modern fluvial sediments to constrain long-term (~103 yr) erosion rate averaged on the catchment area. 35 longitudinal rivers profiles have been analyzed to study the tectonic signal on the landscape evolution. The rivers analyzed exhibit a wide variety of profile forms, diverging from equilibrium state form. Generally the river profiles show at least 2 and often 3 distinct concave-up knickpoint-bounded segments, characterized by different value of concavity and steepness indices. River profiles suggest three main stages of incision. The values of ks and θ in the lower segments evidence a decrease in river incision, due probably to increasing uplift rate. The cosmogenic erosion rates pointed out that old landscape upland is eroding slowly at ~0.1 mm/yr. In the contrary, the flanks of the massif is eroding faster with value from 0.4 to 0.5 mm/yr due to river incision and hillslope processes. Cosmogenic erosion rates mach linearly with steepness indices and with average hillslope gradient. In the Messina area the long term erosion rate from low-T thermochronometry are of the same order than millennium scale cosmogenic erosion rate (1-2 mm/yr). In this part of the chain the fast erosion is active since several million years, probably controlled by extensional tectonic regime. In the Peloritani Mts apatite fission-track and (U-Th)/He thermochronometry are applied to constraint the thermal history of the basement rock. Apatite fission-track ages range between 29.0±5.5 and 5.5±0.9 Ma while apatite (U-Th)/He ages vary from 19.4 to 1.0 Ma. Most of the AFT ages are younger than the overlying terrigenous sequence that in turn postdates the main orogenic phase. Through the coupling of the thermal modelling with the stratigraphic record, a Middle Miocene thermal event due to tectonic burial is unravel. This event affected a inner-intermediate portion of the Peloritani belt confined by young AFT data (<15 Ma) distribution. We interpret this thermal event as due to an out-of–sequence thrusting occurring in the inner portion of the belt. Young (U-Th)/He ages (c. 5 Ma) record a final exhumation stage with increasing rates of denudation since the Pliocene times due to postorogenic extensional tectonics and regional uplift. In the final chapter we change the spatial scale to insert digital topography analysis and field data within a geodynamic model that can explain surface evidence produced by subduction process.

Genomic and transcriptional analysis of allergen genes in apple (Malus x domestica)

Apple consumption is highly recomended for a healthy diet and is the most important fruit produced in temperate climate regions. Unfortunately, it is also one of the fruit that most ofthen provoks allergy in atopic patients and the only treatment available up to date for these apple allergic patients is the avoidance. Apple allergy is due to the presence of four major classes of allergens: Mal d 1 (PR-10/Bet v 1-like proteins), Mal d 2 (Thaumatine-like proteins), Mal d 3 (Lipid transfer protein) and Mal d 4 (profilin). In this work new advances in the characterization of apple allergen gene families have been reached using a multidisciplinary approach. First of all, a genomic approach was used for the characterization of the allergen gene families of Mal d 1 (task of Chapter 1), Mal d 2 and Mal d 4 (task of Chapter 5). In particular, in Chapter 1 the study of two large contiguos blocks of DNA sequences containing the Mal d 1 gene cluster on LG16 allowed to acquire many new findings on number and orientation of genes in the cluster, their physical distances, their regulatory sequences and the presence of other genes or pseudogenes in this genomic region. Three new members were discovered co-localizing with the other Mal d 1 genes of LG16 suggesting that the complexity of the genetic base of allergenicity will increase with new advances. Many retrotranspon elements were also retrieved in this cluster. Due to the developement of molecular markers on the two sequences, the anchoring of the physical and the genetic map of the region has been successfully achieved. Moreover, in Chapter 5 the existence of other loci for the Thaumatine-like protein family in apple (Mal d 2.03 on LG4 and Mal d 2.02 on LG17) respect the one reported up to now was demonstred for the first time. Also one new locus for profilins (Mal d 4.04) was mapped on LG2, close to the Mal d 4.02 locus, suggesting a cluster organization for this gene family, as is well reported for Mal d 1 family. Secondly, a methodological approach was used to set up an highly specific tool to discriminate and quantify the expression of each Mal d 1 allergen gene (task of Chapter 2). In aprticular, a set of 20 Mal d 1 gene specific primer pairs for the quantitative Real time PCR technique was validated and optimized. As a first application, this tool was used on leaves and fruit tissues of the cultivar Florina in order to identify the Mal d 1 allergen genes that are expressed in different tissues. The differential expression retrieved in this study revealed a tissue-specificity for some Mal d 1 genes: 10/20 Mal d 1 genes were expressed in fruits and, indeed, probably more involved in the allergic reactions; while 17/20 Mal d 1 genes were expressed in leaves challenged with the fungus Venturia inaequalis and therefore probably interesting in the study of the plant defense mechanism. In Chapter 3 the specific expression levels of the 10 Mal d 1 isoallergen genes, found to be expressed in fruits, were studied for the first time in skin and flesh of apples of different genotypes. A complex gene expression profile was obtained due to the high gene-, tissue- and genotype-variability. Despite this, Mal d 1.06A and Mal d 1.07 expression patterns resulted particularly associated with the degree of allergenicity of the different cultivars. They were not the most expressed Mal d 1 genes in apple but here it was hypotized a relevant importance in the determination of allergenicity for both qualitative and quantitative aspects of the Mal d 1 gene expression levels. In Chapter 4 a clear modulation for all the 17 PR-10 genes tested in young leaves of Florina after challenging with the fungus V. inaequalis have been reported but with a peculiar expression profile for each gene. Interestingly, all the Mal d 1 genes resulted up-regulated except Mal d 1.10 that was down-regulated after the challenging with the fungus. The differences in direction, timing and magnitude of induction seem to confirm the hypothesis of a subfunctionalization inside the gene family despite an high sequencce and structure similarity. Moreover, a modulation of PR-10 genes was showed both in compatible (Gala-V. inaequalis) and incompatible (Florina-V. inaequalis) interactions contribute to validate the hypothesis of an indirect role for at least some of these proteins in the induced defense responses. Finally, a certain modulation of PR-10 transcripts retrieved also in leaves treated with water confirm their abilty to respond also to abiotic stress. To conclude, the genomic approach used here allowed to create a comprehensive inventory of all the genes of allergen families, especially in the case of extended gene families like Mal d 1. This knowledge can be considered a basal prerequisite for many further studies. On the other hand, the specific transcriptional approach make it possible to evaluate the Mal d 1 genes behavior on different samples and conditions and therefore, to speculate on their involvement on apple allergenicity process. Considering the double nature of Mal d 1 proteins, as apple allergens and as PR-10 proteins, the gene expression analysis upon the attack of the fungus created the base for unravel the Mal d 1 biological functions. In particular, the knowledge acquired in this work about the PR-10 genes putatively more involved in the specific Malus-V. inaequalis interaction will be helpful, in the future, to drive the apple breeding for hypo-allergenicity genotype without compromise the mechanism of response of the plants to stress conditions. For the future, the survey of the differences in allergenicity among cultivars has to be be thorough including other genotypes and allergic patients in the tests. After this, the allelic diversity analysis with the high and low allergenic cultivars on all the allergen genes, in particular on the ones with transcription levels correlated to allergencity, will provide the genetic background of the low ones. This step from genes to alleles will allow the develop of molecular markers for them that might be used to effectively addressed the apple breeding for hypo-allergenicity. Another important step forward for the study of apple allergens will be the use of a specific proteomic approach since apple allergy is a multifactor-determined disease and only an interdisciplinary and integrated approach can be effective for its prevention and treatment.

Analytical challenges in the fields of Nanobioscience and Nanobiotecnology: integrated methods for separation and characterization

Nano(bio)science and nano(bio)technology play a growing and tremendous interest both on academic and industrial aspects. They are undergoing rapid developments on many fronts such as genomics, proteomics, system biology, and medical applications. However, the lack of characterization tools for nano(bio)systems is currently considered as a major limiting factor to the final establishment of nano(bio)technologies. Flow Field-Flow Fractionation (FlFFF) is a separation technique that is definitely emerging in the bioanalytical field, and the number of applications on nano(bio)analytes such as high molar-mass proteins and protein complexes, sub-cellular units, viruses, and functionalized nanoparticles is constantly increasing. This can be ascribed to the intrinsic advantages of FlFFF for the separation of nano(bio)analytes. FlFFF is ideally suited to separate particles over a broad size range (1 nm-1 μm) according to their hydrodynamic radius (rh). The fractionation is carried out in an empty channel by a flow stream of a mobile phase of any composition. For these reasons, fractionation is developed without surface interaction of the analyte with packing or gel media, and there is no stationary phase able to induce mechanical or shear stress on nanosized analytes, which are for these reasons kept in their native state. Characterization of nano(bio)analytes is made possible after fractionation by interfacing the FlFFF system with detection techniques for morphological, optical or mass characterization. For instance, FlFFF coupling with multi-angle light scattering (MALS) detection allows for absolute molecular weight and size determination, and mass spectrometry has made FlFFF enter the field of proteomics. Potentialities of FlFFF couplings with multi-detection systems are discussed in the first section of this dissertation. The second and the third sections are dedicated to new methods that have been developed for the analysis and characterization of different samples of interest in the fields of diagnostics, pharmaceutics, and nanomedicine. The second section focuses on biological samples such as protein complexes and protein aggregates. In particular it focuses on FlFFF methods developed to give new insights into: a) chemical composition and morphological features of blood serum lipoprotein classes, b) time-dependent aggregation pattern of the amyloid protein Aβ1-42, and c) aggregation state of antibody therapeutics in their formulation buffers. The third section is dedicated to the analysis and characterization of structured nanoparticles designed for nanomedicine applications. The discussed results indicate that FlFFF with on-line MALS and fluorescence detection (FD) may become the unparallel methodology for the analysis and characterization of new, structured, fluorescent nanomaterials.

Electrochemistry of carbon based engineered structures

The main aims of my PhD research work have been the investigation of the redox, photophysical and electronic properties of carbon nanotubes (CNT) and their possible uses as functional substrates for the (electro)catalytic production of oxygen and as molecular connectors for Quantum-dot Molecular Automata. While for CNT many and diverse applications in electronics, in sensors and biosensors field, as a structural reinforcing in composite materials have long been proposed, the study of their properties as individual species has been for long a challenging task. CNT are in fact virtually insoluble in any solvent and, for years, most of the studies has been carried out on bulk samples (bundles). In Chapter 2 an appropriate description of carbon nanotubes is reported, about their production methods and the functionalization strategies for their solubilization. In Chapter 3 an extensive voltammetric and vis-NIR spectroelectrochemical investigation of true solutions of unfunctionalized individual single wall CNT (SWNT) is reported that permitted to determine for the first time the standard electrochemical potentials of reduction and oxidation as a function of the tube diameter of a large number of semiconducting SWNTs. We also established the Fermi energy and the exciton binding energy for individual tubes in solution and, from the linear correlation found between the potentials and the optical transition energies, one to calculate the redox potentials of SWNTs that are insufficiently abundant or absent in the samples. In Chapter 4 we report on very efficient and stable nano-structured, oxygen-evolving anodes (OEA) that were obtained by the assembly of an oxygen evolving polyoxometalate cluster, (a totally inorganic ruthenium catalyst) with a conducting bed of multiwalled carbon nanotubes (MWCNT). Here, MWCNT were effectively used as carrier of the polyoxometallate for the electrocatalytic production of oxygen and turned out to greatly increase both the efficiency and stability of the device avoiding the release of the catalysts. Our bioinspired electrode addresses the major challenge of artificial photosynthesis, i.e. efficient water oxidation, taking us closer to when we might power the planet with carbon-free fuels. In Chapter 5 a study on surface-active chiral bis-ferrocenes conveniently designed in order to act as prototypical units for molecular computing devices is reported. Preliminary electrochemical studies in liquid environment demonstrated the capability of such molecules to enter three indistinguishable oxidation states. Side chains introduction allowed to organize them in the form of self-assembled monolayers (SAM) onto a surface and to study the molecular and redox properties on solid substrates. Electrochemical studies on SAMs of these molecules confirmed their attitude to undergo fast (Nernstian) electron transfer processes generating, in the positive potential region, either the full oxidized Fc+-Fc+ or the partly oxidized Fc+-Fc species. Finally, in Chapter 6 we report on a preliminary electrochemical study of graphene solutions prepared according to an original procedure recently described in the literature. Graphene is the newly-born of carbon nanomaterials and is certainly bound to be among the most promising materials for the next nanoelectronic generation.

Geological and Structural evolution of the Eurasia Africa plate boundary in the Gulf of Cadiz Central Eastern Atlantic Sea.

Iberia Africa plate boundary, cross, roughly W-E, connecting the eastern Atlantic Ocean from Azores triple junction to the Continental margin of Morocco. Relative movement between the two plate change along the boundary, from transtensive near the Azores archipelago, through trascurrent movement in the middle at the Gloria Fracture Zone, to transpressive in the Gulf of Cadiz area. This study presents the results of geophysical and geological analysis on the plate boundary area offshore Gibraltar. The main topic is to clarify the geodynamic evolution of this area from Oligocene to Quaternary. Recent studies have shown that the new plate boundary is represented by a 600 km long set of aligned, dextral trascurrent faults (the SWIM lineaments) connecting the Gloria fault to the Riff orogene. The western termination of these lineaments crosscuts the Gibraltar accretionary prism and seems to reach the Moroccan continental shelf. In the past two years newly acquired bathymetric data collected in the Moroccan offshore permit to enlighten the present position of the eastern portion of the plate boundary, previously thought to be a diffuse plate boundary. The plate boundary evolution, from the onset of compression in the Oligocene to the Late Pliocene activation of trascurrent structures, is not yet well constrained. The review of available seismics lines, gravity and bathymetric data, together with the analysis of new acquired bathymetric and high resolution seismic data offshore Morocco, allows to understand how the deformation acted at lithospheric scale under the compressive regime. Lithospheric folding in the area is suggested, and a new conceptual model is proposed for the propagation of the deformation acting in the brittle crust during this process. Our results show that lithospheric folding, both in oceanic and thinned continental crust, produced large wavelength synclines bounded by short wavelength, top thrust, anticlines. Two of these anticlines are located in the Gulf of Cadiz, and are represented by the Gorringe Ridge and Coral Patch seamounts. Lithospheric folding probably interacted with the Monchique – Madeira hotspot during the 72 Ma to Recent, NNE – SSW transit. Plume related volcanism is for the first time described on top of the Coral Patch seamount, where nine volcanoes are found by means of bathymetric data. 40Ar-39Ar age of 31.4±1.98 Ma are measured from one rock sample of one of these volcanoes. Analysis on biogenic samples show how the Coral Patch act as a starved offshore seamount since the Chattian. We proposed that compression stress formed lithospheric scale structures playing as a reserved lane for the upwelling of mantle material during the hotspot transit. The interaction between lithospheric folding and the hotspot emplacement can be also responsible for the irregularly spacing, and anomalous alignments, of individual islands and seamounts belonging to the Monchique - Madeira hotspot.

Resistenza di travi metalliche a doppio T con irrigidimenti longitudinali soggette a carichi trasversali concentrati

The thesis deals with the patch loading of I-girder with two longitudinal stiffeners. The configuration with two longitudinal stiffeners is often an excellent solution for beams of higher than 3 meters but has not yet been discussed in EN 1993-1-5. It is proposed a model of resistance harmonized with the methods used in Eurocodes for the other problems of buckling. The model contains three significant parts: the yield resistance, the elastic critical load used to determine the slenderness parameter and a reduction factor that relates the resistance to the slenderness. The thesis is structured into eight chapters, in addition to Preface and Table of Contents. Chapter 3 is a list of all symbols used. Chapter 4 presents a review of earlier works. Chapter 5 details the experimental investigations conducted by Gozzi (2007) on three samples without longitudinal stiffeners. Due to the difficulty of completing a personal physical model testing during the doctorate, it was decided to carefully study the laboratory work by Gozzi and use it as a basis for the calibration of the numerical study. In Chapter 6 is presented the first part of the numerical study. At this stage, the laboratory tests conducted by Gozzi have been reproduced through a finite element model. It is observed a good agreement of numerical results with test data. In Chapter 7 summarizes the results of numerical analysis of the girder with two longitudinal stiffeners. Chapter 8 presents the procedure proposed for calculating the ultimate patch loading resistance of the girder with two longitudinal stiffeners. Chapter 9 contains a summary of work done in this thesis with suggestions for the most important issues for future development. Chapter 10 lists the references. There are also three appendices with test data by Gozzi and data obtained from literature.

Role of Notch signalling in human hepatocellular carcinoma

The Notch signalling is a cellular pathway that results conserved from Drosophila to Homo sapiens controlling a wide range of cellular processes in development and in differentiated organs. It induces cell proliferation or differentiation, increased survival or apoptosis, and it is involved in stemness maintainance. These functions are conserved, but exerted with a high tissue and cellular context specificity. Signalling activation determs nuclear translocation of the receptor’s cytoplasmic domain and activation of target genes transcription. As many developmental pathway, Notch deregulation is involved in cancer, leading to oncogenic or tumour suppressive role depending on the functions exerted in normal tissue. Notch1 and Notch3 resulted aberrantly expressed in human hepatocellular carcinoma (HCC) that is the more frequent tumour of the liver and the sixth most common tumour worldwide. This thesis has the aim to investigate the role of the signalling in HCC, with particular attention to dissect common and uncommon regulatory pathways between Notch1 and Notch3 and to define the role of the signalling in HCC. Nocth1 and Notch3 were analysed on their regulation on Hes1 target and involvement in cell cycle control. They showed to regulate CDKN1C/p57kip2 expression through Hes1 target. CDKN1C/p57kip2 induces not only cell cycle arrest, but also senescence in HCC cell lines. Moreover, the involvement of Notch1 in cancer progression and epithelial to mesenchymal transition was investigated. Notch1 showed to induce invasion of HCC, regulating EMT and E- Cadherin expression. Moreover, Notch3 showed specific regulation on p53 at post translational levels. In vitro and ex vivo analysis on HCC samples suggests a complex role of both receptors in regulate HCC, with an oncogenic role but also showing tumour suppressive effects, suggesting a complex and deep involvement of this signalling in HCC.

Rilievi anatomo-patologici e batteriologici condotti sull’apparato gastroenterico di una metapopolazione di cinghiali (Sus scrofa)

Nell’ambito della patologia gastroenterica del suino sono comprese alcune malattie sostenute da batteri spirillari gram negativi, di cui sono disponibili numerose trattazioni riguardanti, soprattutto, l'aspetto epidemiologico e patogenetico. Per alcuni di questi agenti microbici, e per le relative manifestazioni patologiche, poco si conosce nel cinghiale selvatico, animale correlato filogeneticamente al suino domestico, ma compreso in un’ecologia completamente differente. Da queste premesse è nato un approccio di ricerca e studio del comportamento di questi microrganismi in una metapopolazione di cinghiali, abbattuti durante il piano di controllo della popolazione densità-dipendente nel Parco dei Gessi e Calanchi dell’Abbadessa (BO), cercando di rapportare le conoscenze riportate in letteratura sul suino domestico con quanto è scaturito dalle indagini condotte sul cinghiale selvatico. In particolare è stata indagata con metodica immunoistochimica la presenza di Lawsonia intracellularis, patogeno del suino responsabile di Enterite Proliferativa (EP), in secondo luogo sono state condotte indagini batteriologiche e istologiche da stomaco e intestino, finalizzate all’isolamento di microrganismi spirillari dei generi Campylobacter e Helicobacter, da correlare all’eventuale presenza di lesioni infiammatorie e ulcerative gastriche o enteriche valutate secondo sistemi a punteggio ottenuti dalla bibliografia o realizzati in base alla tipologia di infiltrato cellulare e alla sua localizzazione. In ultimo, a fini comparativi con uno studio condotto nel 2002-2004 nello steso Parco Regionale, sono stati monitorati i livelli di antibioticoresistenza di indicatori fecali usando metodiche internazionali standardizzate (Escherichia coli e Enterococcus faecium.) nonché su un numero significativo di isolati di Campylobacter lanienae, per ottenere indicazioni preliminari sull’andamento nei 10 anni trascorsi dello stato di inquinamento da farmaco del Parco stesso. I risultati ottenuti permettono di ampliare le conoscenze sulla flora enterica del cinghiale selvatico e pongono questioni di sicurezza pubblica sulla gestione dei mammiferi selvatici.

Clinicopathologic findings in thoroughbred horses during a high speed – short term competition

The aim of this study was to examine whether a real high speed-short term competition influences clinicopathological data focusing on muscle enzymes, iron profile and Acute Phase Proteins. 30 Thoroughbred racing horses (15 geldings and 15 females) aged between 4-12 years (mean 7 years), were used for the study. All the animals performed a high speed-short term competition for a total distance of 154 m in about 12 seconds, repeated 8 times, within approximately one hour (Niballo Horse Race). Blood samples were obtained 24 hours before and within 30 minutes after the end of the races. On all samples were performed a complete blood count (CBC), biochemical and haemostatic profiles. The post-race concentrations for the single parameter were corrected using an estimation of the plasma volume contraction according to the individual Alb concentration. Data were analysed with descriptive statistics and the percentage of variation from the baseline values were recorded. Pre- and post-race results were compared with non-parametric statistics (Mann Whitney U test). A difference was considered significant at p<0.05. A significant plasma volume contraction after the race was detected (Hct, Alb; p<0.01). Other relevant findings were increased concentrations of muscular enzymes (CK, LDH; p<0.01), Crt (p<0.01), significant increased uric acid (p<0.01), a significant decrease of haptoglobin (p<0.01) associated to an increase of ferritin concentrations (p<0.01), significant decrease of fibrinogen (p<0.05) accompanied by a non-significant increase of D-Dimers concentrations (p=0.08). This competition produced relevant abnormalities on clinical pathology in galloping horses. This study confirms a significant muscular damage, oxidative stress, intravascular haemolysis and subclinical hemostatic alterations. Further studies are needed to better understand the pathogenesis, the medical relevance and the impact on performance of these alterations in equine sport medicine.

Measurement of the $B^0$ - $\bar{B}^0$ and $B^0_s$ - $\bar{B}^0_s$ production asymmetries in pp collisions at $\sqrt{s}=7$ TeV and $\sqrt{s}=8$ TeV with the LHCb experiment

The production rate of $b$ and $\bar{b}$ hadrons in $pp$ collisions are not expected to be strictly identical, due to imbalance between quarks and anti-quarks in the initial state. This phenomenon can be naively related to the fact that the $\bar{b}$ quark produced in the hard scattering might combine with a $u$ or $d$ valence quark from the colliding protons, whereas the same cannot happen for a $b$ quark. This thesis presents the analysis performed to determine the production asymmetries of $B^0$ and $B^0_s$. The analysis relies on data samples collected by the LHCb detector at the Large Hadron Collider (LHC) during the 2011 and 2012 data takings at two different values of the centre of mass energy $\sqrt{s}=7$ TeV and at $\sqrt{s}=8$ TeV, corresponding respectively to an integrated luminosity of 1 fb$^{-1}$ and of 2 fb$^{-1}$. The production asymmetry is one of the key ingredients to perform measurements of $CP$ violation in b-hadron decays at the LHC, since $CP$ asymmetries must be disentangled from other sources. The measurements of the production asymmetries are performed in bins of $p_\mathrm{T}$ and $\eta$ of the $B$-meson. The values of the production asymmetries, integrated in the ranges $4 < p_\mathrm{T} < 30$ GeV/c and $2.5<\eta<4.5$, are determined to be: \begin{equation} A_\mathrm{P}(\B^0)= (-1.00\pm0.48\pm0.29)\%,\nonumber \end{equation} \begin{equation} A_\mathrm{P}(\B^0_s)= (\phantom{-}1.09\pm2.61\pm0.61)\%,\nonumber \end{equation} where the first uncertainty is statistical and the second is systematic. The measurement of $A_\mathrm{P}(B^0)$ is performed using the full statistics collected by LHCb so far, corresponding to an integrated luminosity of 3 fb$^{-1}$, while the measurement of $A_\mathrm{P}(B^0_s)$ is realized with the first 1 fb$^{-1}$, leaving room for improvement. No clear evidence of dependences on the values of $p_\mathrm{T}$ and $\eta$ is observed. The results presented in this thesis are the most precise measurements available up to date.