Petrology and geochemistry of Lipari Island (Aeolian archipelago): constraints on magma genesis and evolution

A full set of geochemical and Sr, Nd and Pb isotope data both on bulk-rock and mineral samples is provided for volcanic rocks representative of the whole stratigraphic succession of Lipari Island in the Aeolian archipelago. These data, together with petrographic observations and melt/fluid inclusion investigations from the literature, give outlines on the petrogenesis and evolution of magmas through the magmatic and eruptive history of Lipari. This is the result of nine successive Eruptive Epochs developing between 271 ka and historical times, as derived from recentmost volcanological and stratigraphic studies, combined with available radiometric ages and correlation of tephra layers and marine terrace deposits. These Eruptive Epochs are characterized by distinctive vents partly overlapping in space and time, mostly under control of the main regional tectonic trends (NNW-SSE, N-S and minor E-W). A large variety of lava flows, scoriaceous deposits, lava domes, coulees and pyroclastics are emplaced, ranging in composition through time from calcalkaline (CA) and high-K (HKCA) basaltic andesites to rhyolites. CA and HKCA basaltic andesitic to dacitic magmas were erupted between 271 and 81 ka (Eruptive Epochs 1-6) from volcanic edifices located along the western coast of the island (and subordinately the eastern Monterosa) and the M.Chirica and M.S.Angelo stratocones. These mafic to intermediate magmas mainly evolved through AFC and RAFC processes, involving fractionation of mafic phases, assimilation of wall rocks and mixing with newly injected mafic magmas. Following a 40 ka-long period of volcanic quiescence, the rhyolitic magmas were lately erupted from eruptive vents located in the southern and north-eastern sectors of Lipari between 40 ka and historical times (Eruptive Epochs 7-9). They are suggested to derive from the previous mafic to intermediate melts through AFC processes. During the early phases of rhyolitic magmatism (Eruptive Epochs 7-8), enclaves-rich rocks and banded pumices, ranging in composition from HKCA dacites to low-SiO2 rhyolites were erupted, representing the products of magma mixing between fresh mafic magmas and the fractionated rhyolitic melts. The interaction of mantle-derived magmas with the crust represents an essential process during the whole magmatic hystory of Lipari, and is responsible for the wide range of observed geochemical and isotopic variations. The crustal contribution was particularly important during the intermediate phases of activity of Lipari when the cordierite-bearing lavas were erupted from the M. S.Angelo volcano (Eruptive Epoch 5, 105 ka). These lavas are interpreted as the result of mixing and subsequent hybridization of mantle-derived magmas, akin to the ones characterizing the older phases of activity of Lipari (Eruptive Epochs 1-4), and crustal anatectic melts derived from dehydration-melting reactions of metapelites in the lower crust. A comparison between the adjacent islands of Lipari and Vulcano outlines that their mafic to intermediate magmas seem to be genetically connected and derive from a similar mantle source affected by different degrees of partial melting (and variable extent of crustal assimilation) producing either the CA magmas of Lipari (higher degrees) or the HKCA to SHO magmas of Vulcano (lower degrees). On a regional scale, the most primitive rocks (SiO2<56%, MgO>3.5%) of Lipari, Vulcano, Salina and Filicudi are suggested to derive from a similar MORB-like source, variably metasomatized by aqueous fluids coming from the slab and subordinately by the additions of sediments.

Constraints meet concurrency

We investigate the benefits that emerge when the fields of constraint programming and concurrency meet. On one hand, constraints can be use in concurrency theory to increase the conciseness and the expressive power of concurrent languages from a pragmatic point of view. On the other hand, problems modeled by using constraints can be solved faster and more efficiently using a concurrent system. We explore both directions providing two separate lines of contribution. Firstly we study the expressive power of a concurrent language, namely Constraint Handling Rules, that supports constraints as a primitive construct. We show what features of this language make it Turing powerful. Then we propose a framework to solve constraint problems that is intended to be deployed on a concurrent system. For the development of this framework we used the concurrent language Jolie following the Service Oriented paradigm. Based on this experience, we also propose an extension to Service Oriented Languages to overcome some of their limitations and to improve the development of concurrent applications.

Social learning and action understanding in human observers: contributions of sensori-motor constraints and prior information

The aim of this thesis was to investigate the respective contribution of prior information and sensorimotor constraints to action understanding, and to estimate their consequences on the evolution of human social learning. Even though a huge amount of literature is dedicated to the study of action understanding and its role in social learning, these issues are still largely debated. Here, I critically describe two main perspectives. The first perspective interprets faithful social learning as an outcome of a fine-grained representation of others’ actions and intentions that requires sophisticated socio-cognitive skills. In contrast, the second perspective highlights the role of simpler decision heuristics, the recruitment of which is determined by individual and ecological constraints. The present thesis aims to show, through four experimental works, that these two contributions are not mutually exclusive. A first study investigates the role of the inferior frontal cortex (IFC), the anterior intraparietal area (AIP) and the primary somatosensory cortex (S1) in the recognition of other people’s actions, using a transcranial magnetic stimulation adaptation paradigm (TMSA). The second work studies whether, and how, higher-order and lower-order prior information (acquired from the probabilistic sampling of past events vs. derived from an estimation of biomechanical constraints of observed actions) interacts during the prediction of other people’s intentions. Using a single-pulse TMS procedure, the third study investigates whether the interaction between these two classes of priors modulates the motor system activity. The fourth study tests the extent to which behavioral and ecological constraints influence the emergence of faithful social learning strategies at a population level. The collected data contribute to elucidate how higher-order and lower-order prior expectations interact during action prediction, and clarify the neural mechanisms underlying such interaction. Finally, these works provide/open promising perspectives for a better understanding of social learning, with possible extensions to animal models.

Markov Constraints for Generating Texts with Style

This thesis addresses the issue of generating texts in the style of an existing author, that also satisfy structural constraints imposed by the genre of the text. Although Markov processes are known to be suitable for representing style, they are difficult to control in order to satisfy non-local properties, such as structural constraints, that require long distance modeling. The framework of Constrained Markov Processes allows to precisely generate texts that are consistent with a corpus, while being controllable in terms of rhymes and meter. Controlled Markov processes consist in reformulating Markov processes in the context of constraint satisfaction. The thesis describes how to represent stylistic and structural properties in terms of constraints in this framework and how this approach can be used for the generation of lyrics in the style of 60 differents authors An evaluation of the desctibed method is provided by comparing it to both pure Markov and pure constraint-based approaches. Finally the thesis describes the implementation of an augmented text editor, called Perec. Perec is intended to improve creativity, by helping the user to write lyrics and poetry, exploiting the techniques presented so far.

Designing Electricity Auctions in the Presence of Transmission Constraints

This paper analyzes the effect that different designs in the access to fnancial transmission rights has on spot electricity auctions. In particular, I characterize the equilibrium in the spot electricity market when financial transmission rights are assigned to the grid operator and when financial transmission rights are assigned to the firm that submits the lowest bid in the spot electricity auction. When financial transmission rights are assigned to the grid operator, my model, in contrast with the models available in the literature, works out the equilibrium for any transmission capacity. Moreover, I have found that an increase in transmission capacity not only increases competition between markets but also within a single market. When financial transmission rights are assigned to the firm that submits the lowest bid in the spot electricity auction, firms compete not only for electricity demand, but also for transmission rights and the arbitrage profits derived from its hold. I have found that introduce competition for transmission rights reduces competition in spot electricity auctions.

Constraints on neutrino mass fraction using Redshift Space Distortions

Redshift Space Distortions (RSD) are an apparent anisotropy in the distribution of galaxies due to their peculiar motion. These features are imprinted in the correlation function of galaxies, which describes how these structures distribute around each other. RSD can be represented by a distortions parameter $\beta$, which is strictly related to the growth of cosmic structures. For this reason, measurements of RSD can be exploited to give constraints on the cosmological parameters, such us for example the neutrino mass. Neutrinos are neutral subatomic particles that come with three flavours, the electron, the muon and the tau neutrino. Their mass differences can be measured in the oscillation experiments. Information on the absolute scale of neutrino mass can come from cosmology, since neutrinos leave a characteristic imprint on the large scale structure of the universe. The aim of this thesis is to provide constraints on the accuracy with which neutrino mass can be estimated when expoiting measurements of RSD. In particular we want to describe how the error on the neutrino mass estimate depends on three fundamental parameters of a galaxy redshift survey: the density of the catalogue, the bias of the sample considered and the volume observed. In doing this we make use of the BASICC Simulation from which we extract a series of dark matter halo catalogues, characterized by different value of bias, density and volume. This mock data are analysed via a Markov Chain Monte Carlo procedure, in order to estimate the neutrino mass fraction, using the software package CosmoMC, which has been conveniently modified. In this way we are able to extract a fitting formula describing our measurements, which can be used to forecast the precision reachable in future surveys like Euclid, using this kind of observations.

Next-Generation Sequencing-Based Mutations Scanning Strategy of the BCR-ABL Kinase Domain in Patients with PhiladelPhia-Chromosome Positive Leukemias Treated with Tyrosine Kinase Inhibitors

In chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia patients resistant to tyrosine kinase inhibitors (TKIs), BCR-ABL kinase domain mutation status is an essential component of the therapeutic decision algorithm. The recent development of Ultra-Deep Sequencing approach (UDS) has opened the way to a more accurate characterization of the mutant clones surviving TKIs conjugating assay sensitivity and throughput. We decided to set-up and validated an UDS-based for BCR-ABL KD mutation screening in order to i) resolve qualitatively and quantitatively the complexity and the clonal structure of mutated populations surviving TKIs, ii) study the dynamic of expansion of mutated clones in relation to TKIs therapy, iii) assess whether UDS may allow more sensitive detection of emerging clones, harboring critical 2GTKIs-resistant mutations predicting for an impending relapse, earlier than SS. UDS was performed on a Roche GS Junior instrument, according to an amplicon sequencing design and protocol set up and validated in the framework of the IRON-II (Interlaboratory Robustness of Next-Generation Sequencing) International consortium.Samples from CML and Ph+ ALL patients who had developed resistance to one or multiple TKIs and collected at regular time-points during treatment were selected for this study. Our results indicate the technical feasibility, accuracy and robustness of our UDS-based BCR-ABL KD mutation screening approach. UDS was found to provide a more accurate picture of BCR-ABL KD mutation status, both in terms of presence/absence of mutations and in terms of clonal complexity and showed that BCR-ABL KD mutations detected by SS are only the “tip of iceberg”. In addition UDS may reliably pick 2GTKIs-resistant mutations earlier than SS in a significantly greater proportion of patients.The enhanced sensitivity as well as the possibility to identify low level mutations point the UDS-based approach as an ideal alternative to conventional sequencing for BCR-ABL KD mutation screening in TKIs-resistant Ph+ leukemia patients

Identification of novel genetic alterations in pediatric cytogenetically normal acute myeloid leukemia by next-generation sequencing

Pediatric acute myeloid leukemia (AML) is a molecularly heterogeneous disease that arises from genetic alterations in pathways that regulate self-renewal and myeloid differentiation. While the majority of patients carry recurrent chromosomal translocations, almost 20% of childhood AML do not show any recognizable cytogenetic alteration and are defined as cytogenetically normal (CN)-AML. CN-AML patients have always showed a great variability in response to therapy and overall outcome, underlining the presence of unknown genetic changes, not detectable by conventional analyses, but relevant for pathogenesis, and outcome of AML. The development of novel genome-wide techniques such as next-generation sequencing, have tremendously improved our ability to interrogate the cancer genome. Based on this background, the aim of this research study was to investigate the mutational landscape of pediatric CN-AML patients negative for all the currently known somatic mutations reported in AML through whole-transcriptome sequencing (RNA-seq). RNA-seq performed on diagnostic leukemic blasts from 19 pediatric CN-AML cases revealed a considerable incidence of cryptic chromosomal rearrangements, with the identification of 21 putative fusion genes. Several of the fusion genes that were identified in this study are recurrent and might have a prognostic and/or therapeutic relevance. A paradigm of that is the CBFA2T3-GLIS2 fusion, which has been demonstrated to be a common alteration in pediatric CN-AML, predicting poor outcome. Important findings have been also obtained in the identification of novel therapeutic targets. On one side, the identification of NUP98-JARID1A fusion suggests the use of disulfiram; on the other, here we describe alteration-activating tyrosine kinases, providing functional data supporting the use of tyrosine kinase inhibitors to specifically inhibit leukemia cells. This study provides new insights in the knowledge of genetic alterations underlying pediatric AML, defines novel prognostic markers and putative therapeutic targets, and prospectively ensures a correct risk stratification and risk-adapted therapy also for the “all-neg” AML subgroup.

Caratterizzazione genomica di virus influenzali suini in Italia mediante next generation sequencing

I sottotipi H1N1, H1N2 e H3N2 di influenza A virus sono largamente diffusi nella popolazione suina di tutto il mondo. Nel presente lavoro è stato sviluppato un protocollo di sequenziamento di c.d. nuova generazione, su piattaforma Ion Torrent PGM, idoneo per l’analisi di tutti i virus influenzali suini (SIV). Per valutare l’evoluzione molecolare dei SIV italiani, sono stati sequenziati ed analizzati mediante analisi genomica e filogenetica un totale di sessantadue ceppi di SIV appartenenti ai sottotipi H1N1, H1N2 e H3N2, isolati in Italia dal 1998 al 2014. Sono stati evidenziati in sei campioni due fenomeni di riassortimento: tutti i SIV H1N2 esaminati presentavano una neuraminidasi di derivazione umana, diversa da quella dei SIV H1N2 circolanti in Europa, inoltre l’emoagglutinina (HA) di due isolati H1N2 era originata dal riassortimento con un SIV H1N1 avian-like. L’analisi molecolare dell’HA ha permesso di rivelare un’inserzione di due amminoacidi in quattro SIV H1N1 pandemici e una delezione di due aminoacidi in quattro SIV H1N2, entrambe a livello del sito di legame con il recettore cellulare. E’ stata inoltre evidenziata un’elevata omologia di un SIV H1N1 con ceppi europei isolati negli anni ’80, suggerendo la possibile origine vaccinale di questo virus. E’ stato possibile, in aggiunta, applicare il nuovo protocollo sviluppato per sequenziare un virus influenzale aviare altamente patogeno trasmesso all’uomo, direttamente da campione biologico. La diversità genetica nei SIV esaminati in questo studio conferma l’importanza di un continuo monitoraggio della costellazione genomica dei virus influenzali nella popolazione suina.