Electron identification and reconstruction with the OPERA ECC bricks and search for muon neutrino to electron neutrino oscillations

The procedure for event location in OPERA ECC has been optimazed for penetrating particles while is less efficient for electrons. For this reason new procedure has been defined in order to recover event with an electromagnetic shower in its final state not located with the standard one. The new procedure include the standard procedure during which several electromagnetic shower hint has been defined by means of the available data. In case the event is not located, the presence of an electromagnetic shower hint trigger a dedicated procedure. The old and new location procedure has been then simulated in order to obtain the standard location efficiency and the possible gain due to the new one for the events with electromagnetic shower. Finally a Data-MC comparison has been performed for the 2008 and 2009 runs for what concern the NC in order to validate the Monte Carlo. Then the expected electron neutrino interactions for the 2008 and 2009 runs has been evaluated and compared with the available data.

Lesion detection and classification in breast cancer: evaluation of approaches based on morphological features, tracer kinetic modelling and semi-quantitative parameters in MR functional imaging (DCE-MRI)

The diagnosis, grading and classification of tumours has benefited considerably from the development of DCE-MRI which is now essential to the adequate clinical management of many tumour types due to its capability in detecting active angiogenesis. Several strategies have been proposed for DCE-MRI evaluation. Visual inspection of contrast agent concentration curves vs time is a very simple yet operator dependent procedure, therefore more objective approaches have been developed in order to facilitate comparison between studies. In so called model free approaches, descriptive or heuristic information extracted from time series raw data have been used for tissue classification. The main issue concerning these schemes is that they have not a direct interpretation in terms of physiological properties of the tissues. On the other hand, model based investigations typically involve compartmental tracer kinetic modelling and pixel-by-pixel estimation of kinetic parameters via non-linear regression applied on region of interests opportunely selected by the physician. This approach has the advantage to provide parameters directly related to the pathophysiological properties of the tissue such as vessel permeability, local regional blood flow, extraction fraction, concentration gradient between plasma and extravascular-extracellular space. Anyway, nonlinear modelling is computational demanding and the accuracy of the estimates can be affected by the signal-to-noise ratio and by the initial solutions. The principal aim of this thesis is investigate the use of semi-quantitative and quantitative parameters for segmentation and classification of breast lesion. The objectives can be subdivided as follow: describe the principal techniques to evaluate time intensity curve in DCE-MRI with focus on kinetic model proposed in literature; to evaluate the influence in parametrization choice for a classic bi-compartmental kinetic models; to evaluate the performance of a method for simultaneous tracer kinetic modelling and pixel classification; to evaluate performance of machine learning techniques training for segmentation and classification of breast lesion.

Structural and kinetic characterization of DNA polymerases I and III from Escherichia coli

DNA elongation is performed by Pol III α subunit in E. coli, stimulated by the association with ε and θ subunits. These three subunits define the DNA Pol III catalytic core. There is controversy about the DNA Pol III assembly for the simultaneous control of lagging and leading strands replication, since some Authors propose a dimeric model with two cores, whereas others have assembled in vitro a trimeric DNA Pol III with a third catalytic core, which increases the efficiency of DNA replication. Moreover, the function of the PHP domain, located at the N-terminus of α subunit, is still unknown. Previous studies hypothesized a possible pyrophosphatase activity, not confirmed yet. The present Thesis highlights by the first time the production in vivo of a trimeric E. coli DNA Pol III by co-expressing α, τ, ε and θ subunits. This trimeric complex has been enzymatically characterized and a molecular model has been proposed, with 2 α subunits sustaining the lagging-strand replication whereas the third core replicates the leading strand. In addition, the pyrophosphatase activity of the PHP domain has been confirmed. This activity involves, at least, the H12 and the D19 residues, whereas the D201 regulates phosphate release. On the other hand, an artificial polymerase (HoLaMa), designed by deleting the exonuclease domain of Klenow Fragment, has been expressed, purified and characterized for a better understanding of bacterial polymerases mechanism. The absence of exonuclease domain impaired enzyme processivity, since this domain is involved in DNA binding. Finally, Klenow enzyme, HoLaMa, α subunit and DNA Pol III αεθ have been characterized at the single-molecule level by FRET analysis, combining ALEX and TIRF microscopy. Fluorescently-labeled DNA molecules were immobilized, and changes in FRET efficiency enabled us to study polymerase binding and DNA polymerization.

Kinetic and mechanistic studies on unconventional antioxidant activities of natural compounds

In chapter one, the autoxidation kinetics of natural oil substrates, including, triglyceric sunflower oil, olive oil, terpenic squalene, and p-cymene were calibrated through differential oximetry methods. Calibration allows their use as reference oxidizable substrates for further studies, e.g. for quantitative testing of antioxidants under biomimetic settings. Several essential oils samples, of different botanical species or different productions of same species were studied for their antioxidant activity in inhibited autoxidation kinetics. Their antioxidant activities were matched with their composition analyzed by GC-MS. In chapter two, the molecular mechanism of the synergy between the common phenolic antioxidants such as tocopherol and catechols with widespread essential component gamma-terpinene was studied through lipid oxidation kinetics. Wherein, gamma-terpinene was able to disclose the key intermediacy HOO·, which acted as a reducing agent regenerating the phenolic antioxidant. This counterintuitive role of HOO· radicals was further investigated in detail and allowed to rationalize for the first time the purported antioxidant behavior of PDA melanin nanoparticles. It will also open to a deeper understanding of the redox biology of quinones. Regarding melanin, its role is broadly important in living organisms and its control, including its inhibition, is of great importance with several relevant applications ranging from food preservation to control of human skin pigmentation. In chapter three, an oximetry method combined with the traditional UV-Vis spectroscopy was developed to study the tyrosinase inhibition kinetics, which allowed identifying Glabridin (from G. glabra, L.), as one of the most effective natural tyrosinase inhibitors.

Alpha oscillations index the functionality and the plastic changes of the visual system

Alpha oscillations are linked to visual awareness and to the periodical sampling of visual information, suggesting that alpha rhythm reflect an index of the functionality of the posterior cortices, and hence of the visual system. Therefore, the present work described a series of studies investigating alpha oscillations as a biomarker of the functionality and the plastic modifications of the visual system in response to lesions to the visual cortices or to external stimulations. The studies presented in chapter 5 and 6 showed that posterior lesions alter alpha oscillations in hemianopic patients, with reduced alpha reactivity at the eyes opening and decreased alpha functional connectivity, especially in right-lesioned hemianopics, with concurrent dysfunctions in the theta range, suggesting a specialization of the right hemisphere in orchestrating alpha oscillations and coordinating complex interplays among different brain rhythms. The study presented in chapter 7 investigated a mechanism of rhythmical attentional sampling of visual information in healthy participants, showing that perceptual performance is influenced by a rhythmical mechanism of attentional allocation, occurring at lower-alpha frequencies (i.e., 7 Hz), when a single spatial location is monitored, and at lower frequencies (i.e., 5 Hz), when attention is allocated to two spatial locations. Moreover, the right hemisphere seemed to have a dominance in this rhythmical attentional sampling, distributing attentional resources to the entire visual field. Finally, the study presented in chapter 8 showed that prolonged visual entrainment induce long-term modulations of resting-state alpha activity in healthy participants, suggesting that persistent modifications in the functionality of the visual system are possible. Altogheter, these findings show that functional processes and plastic changes of the visual system are reflected in alpha oscillatory patterns. Therefore, investigating and promoting alpha oscillations may contribute to the development of rehabilitative protocols to ameliorate the functionality of the visual system, in brain lesioned patients.

Ecological responses of Western Palearctic avian species to late Quaternary climate oscillations

This PhD thesis explores the ecological responses of bird species to glacial-interglacial transitions during the late Quaternary in the Western Palearctic, using multiple approaches and at different scales, enhancing the importance of the bird fossil record and quantitative methods to elucidate biotic trends in relation to long-term climate changes. The taxonomic and taphonomic analyses of the avian fossil assemblages from four Italian Middle and Upper Pleistocene sedimentary successions (Grotta del Cavallo, Grotta di Fumane, Grotta di Castelcivita, and Grotta di Uluzzo C) allowed us to reconstruct local-scale patterns in birds’ response to climate changes. These bird assemblages are characterized by the presence of temperate species and by the occasional presence of cold-dwelling species during glacials, related to range shifts. These local patterns are supported by those identified at the continental scale. In this respect, I mapped the present-day and LGM climatic envelopes of species with different climatic requirements. The results show a substantial stability in the range of temperate species and pronounced changes in the range of cold-dwelling species, supported by their fossil records. Therefore, the responses to climate oscillations are highly related to the thermal niches of investigated species. I also clarified the dynamics of the presence of boreal and arctic bird species in Mediterranean Europe, due to southern range shifts, during the glacial phases. After a reassessment of the reliability of the existing fossil evidence, I show that this phenomenon is not as common as previously thought, with important implications for the paleoclimatic and paleoenvironmental significance of the targeted species. I have also been able to explore the potential of multivariate and rarefaction methods in the analyses of avian fossils from Grotta del Cavallo. These approaches helped to delineate the main drivers of taphonomic damages and the dynamics of species diversity in relation to climate-driven paleoenvironmental changes.

Kinetic and mechanistic studies on peroxidation and stabilization of lipids with industrial and biological relevance

Lipid peroxidation is a complex mechanism that causes the degradation of lipid material of both industrial and biological significance. During processing, it is known that thermal stress produces oxidation and polymerization of oils. Additionally, biological lipids with both structural and bioactive roles are prone to peroxidation, which can have pathogenic effects including cancer and long-term degenerative disorders. To create innovative strategies to slow down the deterioration of lipids, it is crucial to improve our understanding of oxidation reactions and kinetics. To this purpose, Chapter II of this thesis focuses on the kinetic study of the oxidation reactions that take place during the thermal processing of bio-oils for industrial application. Through a new method it was possible to evaluate the kinetic parameters of oxidation of various lipid materials. This allowed us to distinguish between the different lipid materials based on their intrinsic properties. The effect of 18 antioxidants from the major families of natural and synthetic phenols were studied using the same methodology in order to acquire crucial data for enhancing the antioxidant activity of phenols based on structure-activity at high temperatures. Finally, it has been described how the antioxidant activity of α-tocopherol, revealed to be scarce in our conditions, can be improved in the presence of gamma-terpinene, through a synergistic action. Chapter III describes the synthesis and study of the antioxidant activity of polydopamine nanoparticles, in order to clarify the unclear mechanism of action of this material. Finally, in Chapter IV it was reported how the gamma-terpinene strongly inhibits the peroxidation of unsaturated lipids in heterogeneous model systems (micelles and liposomes) by forming hydroperoxyl radicals which diffuse outside the lipid nucleus, blocking the propagation of the chain radical. Furthermore, gamma-terpinene shows a very potent protective activity against ferroptosis being effective in the nanomolar range in the human neuroblastoma cell model.

New indicators of star cluster dynamical evolution

This thesis presents a study of globular clusters (GCs), based on analysis of Monte Carlo simulations of globular clusters (GCs) with the aim to define new empirical parameters measurable from observations and able to trace the different phases of their dynamical evolution history. During their long term dynamical evolution, due to mass segregation and and dynamical friction, massive stars transfer kinetic energy to lower-mass objects, causing them to sink toward the cluster center. This continuous transfer of kinetic energy from the core to the outskirts triggers the runaway contraction of the core, known as "core collapse" (CC), followed by episodes of expansion and contraction called gravothermal oscillations. Clearly, such an internal dynamical evolution corresponds to significant variations also of the structure of the system. Determining the dynamical age of a cluster can be challenging as it depends on various internal and external properties. The traditional classification of GCs as CC or post-CC systems relies on detecting a steep power-law cusp in the central density profile, which may not always be reliable due to post-CC oscillations or other processes. In this thesis, based on the normalized cumulative radial distribution (nCRD) within a fraction of the half-mass radius is analyzed, and three diagnostics (A5, P5, and S2.5) are defined. These diagnostics show sensitivity to dynamical evolution and can distinguish pre-CC clusters from post-CC clusters.The analysis performed using multiple simulations with different initial conditions, including varying binary fractions and the presence of dark remnants showed the time variations of the diagnostics follow distinct patterns depending on the binary fraction and the retention or ejection of black holes. This analysis is extended to a larger set of simulations matching the observed properties of Galactic GCs, and the parameters show a potential to distinguish the dynamical stages of the observed clusters as well.