3D probability tomography: theoretical developments and applications to high-resolution geophysical prospecting

The theory of the 3D multipole probability tomography method (3D GPT) to image source poles, dipoles, quadrupoles and octopoles, of a geophysical vector or scalar field dataset is developed. A geophysical dataset is assumed to be the response of an aggregation of poles, dipoles, quadrupoles and octopoles. These physical sources are used to reconstruct without a priori assumptions the most probable position and shape of the true geophysical buried sources, by determining the location of their centres and critical points of their boundaries, as corners, wedges and vertices. This theory, then, is adapted to the geoelectrical, gravity and self potential methods. A few synthetic examples using simple geometries and three field examples are discussed in order to demonstrate the notably enhanced resolution power of the new approach. At first, the application to a field example related to a dipole–dipole geoelectrical survey carried out in the archaeological park of Pompei is presented. The survey was finalised to recognize remains of the ancient Roman urban network including roads, squares and buildings, which were buried under the thick pyroclastic cover fallen during the 79 AD Vesuvius eruption. The revealed anomaly structures are ascribed to wellpreserved remnants of some aligned walls of Roman edifices, buried and partially destroyed by the 79 AD Vesuvius pyroclastic fall. Then, a field example related to a gravity survey carried out in the volcanic area of Mount Etna (Sicily, Italy) is presented, aimed at imaging as accurately as possible the differential mass density structure within the first few km of depth inside the volcanic apparatus. An assemblage of vertical prismatic blocks appears to be the most probable gravity model of the Etna apparatus within the first 5 km of depth below sea level. Finally, an experimental SP dataset collected in the Mt. Somma-Vesuvius volcanic district (Naples, Italy) is elaborated in order to define location and shape of the sources of two SP anomalies of opposite sign detected in the northwestern sector of the surveyed area. The modelled sources are interpreted as the polarization state induced by an intense hydrothermal convective flow mechanism within the volcanic apparatus, from the free surface down to about 3 km of depth b.s.l..

A candidate gene approach to identify DNA markers associated with meat quality and production traits: investigation of several cathepsin genes in Italian heavy pigs.

The cathepsin enzymes represent an important family of lysosomal proteinases with a broad spectrum of functions in many, if not in all, tissues and cell types. In addition to their primary role during the normal protein turnover, they possess highly specific proteolytic activities, including antigen processing in the immune response and a direct role in the development of obesity and tumours. In pigs, the involvement of cathepsin enzymes in proteolytic processes have important effects during the conversion of muscle to meat, due to their influence on meat texture and sensory characteristics, mainly in seasoned products. Their contribution is fundamental in flavour development of dry-curing hams. However, several authors have demonstrated that high cathepsin activity, in particular of cathepsin B, is correlated to defects of these products, such as an excessive meat softness together with abnormal free tyrosine content, astringent or metallic aftertastes and formation of a white film on the cut surface. Thus, investigation of their genetic variability could be useful to identify DNA markers associated with these dry cured hams parameters, but also with meat quality, production and carcass traits in Italian heavy pigs. Unfortunately, no association has been found between cathepsin markers and meat quality traits so far, in particular with cathepsin B activity, suggesting that other genes, besides these, affect meat quality parameters. Nevertheless, significant associations were observed with several carcass and production traits in pigs. A recent study has demonstrated that different single nucleotide polymorphisms (SNPs) localized in cathepsin D (CTSD), F (CTSF), H and Z genes were highly associated with growth, fat deposition and production traits in an Italian Large White pig population. The aim of this thesis was to confirm some of these results in other pig populations and identify new cathepsin markers in order to evaluate their effects on cathepsin activity and other production traits. Furthermore, starting from the data obtained in previous studies on CTSD gene, we also analyzed the known polymorphism located in the insulin-like growth factor 2 gene (IGF2 intron3-g.3072G>A). This marker is considered the causative mutation for the quantitative trait loci (QTL) affecting muscle mass and fat deposition in pigs. Since IGF2 maps very close to CTSD on porcine chromosome (SSC) 2, we wanted to clarify if the effects of the CTSD marker were due to linkage disequilibrium with the IGF2 intron3-g.3072G>A mutation or not. In the first chapter, we reported the results from these two SSC2 gene markers. First of all, we evaluated the effects of the IGF2 intron3-g.3072G>A polymorphism in the Italian Large White breed, for which no previous studies have analysed this marker. Highly significant associations were identified with all estimated breeding values for production and carcass traits (P<0.00001), while no effects were observed for meat quality traits. Instead, the IGF2 intron3-g.3072G>A mutation did not show any associations with the analyzed traits in the Italian Duroc pigs, probably due to the low level of variability at this polymorphic site for this breed. In the same Duroc pig population, significant associations were obtained for the CTSD marker for all production and carcass traits (P < 0.001), after excluding possible confounding effects of the IGF2 mutation. The effects of the CTSD g.70G>A polymorphism were also confirmed in a group of Italian Large White pigs homozygous for the IGF2 intron3-g.3072G allele G (IGF2 intron3-g.3072GG) and by haplotype analysis between the markers of the two considered genes. Taken together, all these data indicated that the IGF2 intron3-g.3072G>A mutation is not the only polymorphism affecting fatness and muscle deposition in pigs. In the second chapter, we reported the analysis of two new SNPs identified in cathepsin L (CTSL) and cathepsin S (CTSS) genes and the association results with meat quality parameters (including cathepsin B activity) and several production traits in an Italian Large White pig population. Allele frequencies of these two markers were evaluated in 7 different pig breeds. Furthermore, we mapped using a radiation hybrid panel the CTSS gene on SSC4. Association studies with several production traits, carried out in 268 Italian Large White pigs, indicated positive effects of the CTSL polymorphism on average daily gain, weight of lean cuts and backfat thickness (P<0.05). The results for these latter traits were also confirmed using a selective genotype approach in other Italian Large White pigs (P<0.01). In the 268 pig group, the CTSS polymorphism was associated with feed:gain ratio and average daily gain (P<0.05). Instead, no association was observed between the analysed markers and meat quality parameters. Finally, we wanted to verify if the positive results obtained for the cathepsin L and S markers and for other previous identified SNPs (cathepsin F, cathepsin Z and their inhibitor cystatin B) were confirmed in the Italian Duroc pig breed (third chapter). We analysed them in two groups of Duroc pigs: the first group was made of 218 performance-tested pigs not selected by any phenotypic criteria, the second group was made of 100 Italian Duroc pigs extreme and divergent for visible intermuscular fat trait. In the first group, the CTSL polymorphism was associated with weight of lean cuts (P<0.05), while suggestive associations were obtained for average daily gain and backfat thickness (P<0.10). Allele frequencies of the CTSL gene marker also differed positively among the visible intermuscular extreme tails. Instead, no positive effects were observed for the other DNA markers on the analysed traits. In conclusion, in agreement with the present data and for the biological role of these enzymes, the porcine CTSD and CTSL markers: a) may have a direct effect in the biological mechanisms involved in determining fat and lean meat content in pigs, or b) these markers could be very close to the putative functional mutation(s) present in other genes. These findings have important practical applications, in particular the CTSD and CTSL mutations could be applied in a marker assisted selection (MAS) both in the Italian Large White and Italian Duroc breeds. Marker assisted selection could also increase in efficiency by adding information from the cathepsin S genotype, but only in the Italian Large White breed.

Experimental analysis of coaxial jets: instability, flow and mixing characterization

The velocity and mixing field of two turbulent jets configurations have been experimentally characterized by means of cold- and hot-wire anemometry in order to investigate the effects of the initial conditions on the flow development. In particular, experiments have been focused on the effect of the separation wall between the two streams on the flow field. The results of the experiments have pointed out that the wake behind a thick wall separating wall has a strong influence on the flow field evolution. For instance, for nearly unitary velocity ratios, a clear vortex shedding from the wall is observable. This phenomenon enhances the mixing between the inner and outer shear layer. This enhancement in the fluctuating activity is a consequence of a local absolute instability of the flow which, for a small range of velocity ratios, behaves as an hydrodynamic oscillator with no sensibility to external perturbations. It has been suggested indeed that this absolute instability can be used as a passive method to control the flow evolution. Finally, acoustic excitation has been applied to the near field in order to verify whether or not the observed vortex shedding behind the separating wall is due to a global oscillating mode as predicted by the theory. A new scaling relationship has been also proposed to determine the preferred frequency for nearly unitary velocity ratios. The proposed law takes into account both the Reynolds number and the velocity ratio dependence of this frequency and, therefore, improves all the previously proposed relationships.

Measurement of top quark pairs production cross-section in the semi-leptonic channel with the ATLAS experiment

This thesis is about three major aspects of the identification of top quarks. First comes the understanding of their production mechanism, their decay channels and how to translate theoretical formulae into programs that can simulate such physical processes using Monte Carlo techniques. In particular, the author has been involved in the introduction of the POWHEG generator in the framework of the ATLAS experiment. POWHEG is now fully used as the benchmark program for the simulation of ttbar pairs production and decay, along with MC@NLO and AcerMC: this will be shown in chapter one. The second chapter illustrates the ATLAS detectors and its sub-units, such as calorimeters and muon chambers. It is very important to evaluate their efficiency in order to fully understand what happens during the passage of radiation through the detector and to use this knowledge in the calculation of final quantities such as the ttbar production cross section. The last part of this thesis concerns the evaluation of this quantity deploying the so-called "golden channel" of ttbar decays, yielding one energetic charged lepton, four particle jets and a relevant quantity of missing transverse energy due to the neutrino. The most important systematic errors arising from the various part of the calculation are studied in detail. Jet energy scale, trigger efficiency, Monte Carlo models, reconstruction algorithms and luminosity measurement are examples of what can contribute to the uncertainty about the cross-section.

Simulazione CAD dell'impingement articolare con protesi d'anca convenzionale e a conservazione di collo in funzione dei principali parametri chirurgici e anatomici

Lo scopo del lavoro è quello di verificare tramite software CAD l’influenza dei principali parametri chirurgici e anatomici sul Range Of Motion (ROM). Sono stati costruiti 5 modelli, uno di articolazione sana(Senza Protesi), uno di protesi Convenzionale e tre di protesi Conservative o a Conservazione (Totale, Media e Bassa Conservazione). Per tutti i modelli sono state simulate le rotazioni di base e i cosiddetti movimenti critici, ovvero quei movimenti a rischio di lussazione. Le prove sono state eseguite per teste da 28-,32-,36-,40mm di diametro, e con la coppa orientata di 45° in abduzione e 15° gradi in antiversione prima e successivamente di 45° e 0°. Inoltre, per verificare l’influenza dell’offset sul ROM, sono stati costruiti e simulati i movimenti per altri 5 modelli che non conservassero il vincolo del mantenere l’offset anatomico. Variando il diametro della testa si registrano differenze apprezzabili in termini di ROM solo per i movimenti di Estensione e Abduzione per il modello di Protesi Convenzionale e di Abduzione per il modello a Bassa Conservazione. Variando il livello di resezione del collo si è visto come per i modelli di protesi a Media Conservazione, Bassa Conservazione e Convenzionale si misurano angoli superiori a quello del riferimento tratto dalla Letteratura. Diversamente per il modello di Protesi a Totale Conservazione i valori ottenuti per alcuni movimenti sono inferiori, poiché limitati da un contatto di tipo c-b. Le simulazioni dei movimenti critici confermano la tendenza di un ROM accettabile per i modelli di protesi a Bassa Conservazione e di protesi Convenzionale, i quali forniscono escursioni angolari sempre superiori a quelle prese come riferimento dalla Letteratura. Invece, le protesi a Totale e Media Conservazione forniscono valori inferiori al riferimento per i movimenti di Pivot e Roll, essendo limitati dall’antiversione della coppa (movimenti di ExtraRotazione e contatto c-b). Variando la posizione della coppa a 45°/0° i due movimenti Critici Pivot e Roll migliorano per i modelli a Totale e Media Conservazione, tornando in linea con il riferimento. Riguardo l’offset si nota come più si avvicina a quello anatomico che misura 46,2mm (da 37 a 44mm), più si riscontra un aumento in termini di ROM.

Potential fields study of Marsili basin and Palinuro volcanic complex

In this thesis Marsili back-arc basin and Palinuro Volcanic Complex (Southern Tyrrhenian Sea) have been investigated by using magnetic, bathymetric and gravimetric data. A new velocity model of opening of the Marsili basin has been proposed, highlighting the transition from the horizontal spreading of the back-arc to the vertical accretion of the Marsili seamount. Introducing gravity data, Marsili's internal structure has been modeled and a huge portion of the volcano with low density and vanishing magnetization has been detected. Forward modeling of Palinuro Volcanic Complex showed as Palinuro represents the shallowest evidence of a deep tectonic discontinuity and the possible transition domain between the oceanic crust of Marsili Basin and the continental crust related to the Appenninic chain.

Depicting the role of CDKN2A/ARF alterations in adult BCR-ABL1-positive acute lymphoblastic leukemia patients: from genomic deletions to prognostic impact

This 9p21 locus, encode for important proteins involved in cell cycle regulation and apoptosis containing the p16/CDKN2A (cyclin-dependent kinase inhibitor 2a) tumor suppressor gene and two other related genes, p14/ARF and p15/CDKN2B. This locus, is a major target of inactivation in the pathogenesis of a number of human tumors, both solid and haematologic, and is a frequent site of loss or deletion also in acute lymphoblastic leukemia (ALL) ranging from 18% to 45% 1. In order to explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive ALL and to investigate their prognostic value, 112 patients (101 de novo and 11 relapse cases) were analyzed by genome-wide single nucleotide polymorphisms arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases. CDKN2A/ARF and CDKN2B genomic alterations were identified in 29% and 25% of newly diagnosed patients, respectively. Deletions were monoallelic in 72% of cases and in 43% the minimal overlapping region of the lost area spanned only the CDKN2A/2B gene locus. The analysis at the time of relapse showed an almost significant increase in the detection rate of CDKN2A/ARF loss (47%) compared to diagnosis (p = 0.06). Point mutations within the 9p21 locus were found at very low level with only a non-synonymous substition in the exon 2 of CDKN2A. Finally, correlation with clinical outcome showed that deletions of CDKN2A/B are significantly associated with poor outcome in terms of overall survival (p = 0.0206), disease free-survival (p = 0.0010) and cumulative incidence of relapse (p = 0.0014). The inactivation of 9p21 locus by genomic deletions is a frequent event in BCR-ABL1-positive ALL. Deletions are frequently acquired at the leukemia progression and work as a poor prognostic marker.

Risposta Immunitaria Epatite B specifica in pazienti affetti da Epatocarcinoma

Hepatitis B x protein (HBx) is a non structural, multifunctional protein of hepatitis B virus (HBV) that modulates a variety of host processes.Due to its transcriptional activity,able to alter the expression of growth-control genes,it has been implicated in hepatocarcinogenesis.Increased expression of HBx has been reported on the liver tissue samples of hepatocellular carcinoma (HCC),and a specific anti-HBx immune response can be detected in the peripheral blood of patients with chronic HBV.However,its role and entity has not been yet clarified.Thus,we performed a cross-sectional analysis of anti-HBx specific T cell response in HBV-infected patients in different stage of disease.A total of 70 HBV-infected subjects were evaluated:15 affected by chronic hepatitis (CH-median age 45 yrs),14 by cirrhosis (median age 55 yrs),11 with dysplastic nodules (median age 64 yrs),15 with HCC (median age 60 yrs),15 with IC(median age 53 yrs).All patients were infected by virus genotype D with different levels of HBV viremia and most of them (91%) were HBeAb positive.The HBx-specific T cell response was evaluated by anti-Interferon (IFN)-gamma Elispot assay after in vitro stimulation of peripheral blood mononuclear cells,using 20 overlapping synthetic peptides covering all HBx protein sequence.HBx-specific IFN-gamma-secreting T cells were found in 6 out of 15 patients with chronic hepatitis (40%), 3 out of 14 cirrhosis (21%), in 5 out of 11 cirrhosis with macronodules (54%), and in 10 out of 15 HCC patients (67%). The number of responding patients resulted significantly higher in HCC than IC (p=0.02) and cirrhosis (p=0.02). Central specific region of the protein x was preferentially recognize,between 86-88 peptides. HBx response does not correlate with clinical feature disease(AFP,MELD).The HBx specific T-cell response seems to increase accordingly to progression of the disease, being increased in subjects with dysplastic or neoplastic lesions and can represent an additional tool to monitor the patients at high risk to develop HCC

Alterazioni del metabolismo osseo e fratture vertebrali dopo trapianto di rene

Introduction:Persistent Hyperparathyroidism after transplantation (HPT),bone disease and vertebral fractures are an important clinical problem in renal transplant patients. Several factors such as renal osteodystrophy, immunosuppressive therapy, deficit/insufficiency Vitamin D may contribute to that.In literature are described different percentages of HPT, vertebral fractures and Osteoporosis/Osteopenia that may be due to the different therapy and to the different employ of steroid. We analyzed 90 patients who received a renal graft between 2005 e 2010. Patients and Methods: 44 male and 46 female. Average age 52,2± 10,1 years, follow-up 31,3±16,6 months, time on dialysis 37±29,6 months. Patients who had creatinine level greater than 2,5 mg/dl were excluded. Immunosuppressive therapy was based on basiliximab, steroids (1.6 to 2 mg/kg/day progressively reduced to 5 mg/day after 45 days from the transplantation) in all patients + calcineurin inhibitor+ mycophenolate mophetil/mycophenolic acid in 88,8% of patients or Everolimus± calcineurin inhibitor in the others. Patients were studied with X-ray of the spine, dual-energy-X-ray, PTH, 25(OH)VitD. Results: 41,1% had HPT; 41,1% had osteopenia at femoral neck and 36,7% at vertebral column; 16,7% had osteoporosis at femoral neck and 15,6% at vertebral column. 10 patients (11%) had vertebral fractures. Patients with normal bone mineral density, compared to those with osteoporosis/osteopenia, are more younger (average age 46,4±11,7 years vs 54.3±8,6); they have spent less time on dialysis (26,5±14,8 months vs 40,7±32,6) and they have values of 25(OH)VitD higher (22,1±7,6 ng/ml vs 17,8±8,5). Patients with vertebral fractures have values of 25(OH)VitD lowest (14,1±6,4 ng/ml vs 19,7±8,5) and they had transplant since more time (29,1±16,2 vs 48,1±8,7 months). There is a significant correlation between HPT and PTH pre transplantation; HPT and levels of VitD (p<0,05) Conclusion: Prevention of Bone disease and vertebral fractures after renal transplant includes: a)treatment before transplantation b)supplementation of vitamin D with cholecalciferol or calcidiol c)shorten the dialysis time.

Satellite and in situ data integrated analysis to study the upper ocean an coastal environment of the Italian seas

The thesis objectives are to develop new methodologies for study of the space and time variability of Italian upper ocean ecosystem through the combined use of multi-sensors satellite data and in situ observations and to identify the capability and limits of remote sensing observations to monitor the marine state at short and long time scales. Three oceanographic basins have been selected and subjected to different types of analyses. The first region is the Tyrrhenian Sea where a comparative analysis of altimetry and lagrangian measurements was carried out to study the surface circulation. The results allowed to deepen the knowledge of the Tyrrhenian Sea surface dynamics and its variability and to defined the limitations of satellite altimetry measurements to detect small scale marine circulation features. Channel of Sicily study aimed to identify the spatial-temporal variability of phytoplankton biomass and to understand the impact of the upper ocean circulation on the marine ecosystem. An combined analysis of the satellite of long term time series of chlorophyll, Sea Surface Temperature and Sea Level field data was applied. The results allowed to identify the key role of the Atlantic water inflow in modulating the seasonal variability of the phytoplankton biomass in the region. Finally, Italian coastal marine system was studied with the objective to explore the potential capability of Ocean Color data in detecting chlorophyll trend in coastal areas. The most appropriated methodology to detect long term environmental changes was defined through intercomparison of chlorophyll trends detected by in situ and satellite. Then, Italian coastal areas subject to eutrophication problems were identified. This work has demonstrated that satellites data constitute an unique opportunity to define the features and forcing influencing the upper ocean ecosystems dynamics and can be used also to monitor environmental variables capable of influencing phytoplankton productivity.

Chlamydia psittaci nel colombo di città: aspetti anatomo-patologici, sierologici e biomolecolari

Scopo del lavoro della presente tesi è stato quello di valutare la prevalenza di Chlamydiaceae, ed in particolare Chlamydia psittaci, in una popolazione aviare con caratteristiche sinantropiche quale il colombo di città (Columba livia var. domestica) dell’areale veneziano. Per evidenziare il patogeno sono state utilizzate metodiche sierologiche, d’isolamento e biomolecolari tradizionali. Contestualmente, mediante tecnologie molecolari innovative, quali microarray ed MLVA (Multilocus VNTR Assay) sono stati valutati i genotipi di C. psittaci e le eventuali altre specie di Chlamydia presenti in tale popolazione. Inoltre, si è proceduto ad una classificazione delle lesioni anatomo-patologiche ed ad una loro correlazione con la presenza del patogeno. I risultati dimostrano che la prevalenza di C. psittaci nella popolazione oggetto dello studio è del 10%. Durante tale studio è stata dimostrata la presenza di un ceppo di C. psittaci atipico, in quanto non classificabile con le attuali tecniche a disposizione. La genotipizzazione dei ceppi di C. psittaci conferma la presenza nel colombo di città del genotipo B, E ed E/B, che solitamente risultano essere coinvolti con minore frequenza in episodi di infezione umana. Inoltre sono stati dimostrati alcuni ceppi classificati come Chlamydia spp., in quanto le metodologie applicate e le conoscenze attuali non permettono ulteriori distinzioni, prospettando la possibilità di un nuovo ceppo. Infine, attraverso l’analisi dei dati raccolti durante la prima fase di campionamenti e successivamente confermati durante la seconda fase, siamo riusciti a strutturare un sistema di selezione, basato su caratteristiche funzionali ed anatomopatologiche, che permette di selezionare in sede necroscopica i colombi molto probabilmente infetti, permettendo conseguentemente una migliore organizzazione e gestione dei campioni di interesse contenendo nel contempo i costi ma mantenendo elevati gli standards diagnostici.

Paleosecular variation of the magnetic field recorded in Pleistocene-holocene volcanics from Pantelleria (italy) and Azores archipelago (portugal): implications for local volcanic history

The primary goal of volcanological studies is to reconstruct the eruptive history of active volcanoes, by correlating and dating volcanic deposits, in order to depict a future scenario and determine the volcanic hazard of an area. However, alternative methods are necessary where the lack of outcrops, the deposit variability and discontinuity make the correlation difficult, and suitable materials for an accurate dating lack. In this thesis, paleomagnetism (a branch of Geophysics studying the remanent magnetization preserved in rocks) is used as a correlating and dating tool. The correlation is based on the assumption that coeval rocks record similar paleomagnetic directions; the dating relies upon the comparison between paleomagnetic directions recorded by rocks with the expected values from references Paleo-Secular Variation curves (PSV, the variation of the geomagnetic field along time). I first used paleomagnetism to refine the knowledge of the pre – 50 ka geologic history of the Pantelleria island (Strait of Sicily, Italy), by correlating five ignimbrites and two breccias deposits emplaced during that period. Since the use of the paleomagnetic dating is limited by the availability of PSV curves for the studied area, I firstly recovered both paleomagnetic directions and intensities (using a modified Thellier method) from radiocarbon dated lava flows in São Miguel (Azores Islands, Portugal), reconstructing the first PSV reference curve for the Atlantic Ocean for the last 3 ka. Afterwards, I applied paleomagnetism to unravel the chronology and characteristics of Holocene volcanic activity at Faial (Azores) where geochronological age constraints lack. I correlated scoria cones and lava flows yielded by the same eruption on the Capelo Peninsula and dated eruptive events (by comparing paleomagnetic directions with PSV from France and United Kingdom), finding that the volcanics exposed at the Capelo Peninsula are younger than previously believed, and entirely comprised in the last 4 ka.