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Barred galaxies in cosmological simulations. Tidal perturbations and feedback.
No full textBars are truly common objects among disc galaxies. Even though it is now commonly accepted that non-axisymmetric structures could deeply affect the life of isolated disc galaxies, by shaping their stellar and gaseous distribution, some fundamental aspects of their formation and growth are still debated. The following manuscript is divided in two parts, in which I contribute to the study of bar formation and evolution through the use of state-of-the-art hydrodynamical and cosmological simulations. In the first part of my work, I investigate the influence of tidal encounters on either unbarred, or already barred systems. Here, I take advantage of two specific simulations belonging to the Eris suite – ErisBH and Eris2k – which evolve two Milky Way-sized barred galaxies in their cosmological volume. I both analyse the direct output of these simulations, and run a sample of new cosmological zoom-in simulations, by altering the original history of galaxy-satellite interactions in the ErisBH run. In the second part, I focus on the analysis of the effect of the different feedback prescriptions implemented in the ErisBH and Eris2k runs. My conclusions depict a scenario where, once the disc has grown to a mass large enough to sustain global non-axisymmetric modes, bar formation is inevitable and tidal encounters have, a destructive effect on the two-fold overdensity. In addition, the self-gravity of the disc and its interplay with various internal processes, seem to be the main drivers of bar formation and growth. I confirm the importance of accurate feedback prescriptions in cosmological zoom-in simulations on the investigated processes, and propose a possible use of a statistical sample of barred galaxies to quantitatively assess this dependence
Il pensiero filosofico e politico di Vito D'Ondes Reggio
No full textMy thesis focuses on the philosophical and political thought of Baron Vito D’Ondes Reggio (Palermo, 1811 - Florence, 1885). The first chapter is about the baron's life, with special emphasis on his intellectual formation, the sources of his thought, and his specific contribution to the pivotal events in Italian history of the 19th century in which he took part: from the Sicilian Revolution of 1848 to his work as a deputy of the Kingdom of Italy; from his parliamentary resignation after the "capture of Rome" (20 September 1870) to the foundation of the "Work of the Congress" (1874). The second chapter analyses his philosophical thought concerning the relationship between the individual, society, and the State. Finally, the third and last chapter introduces D’Ondes Reggio’s theories concerning the “natural” origin of property and his arguments against the “convenitionalist” position
Development of nanostructured supported photocatalysts for hydrogen production and inorganic pollutants removal
No full textSemiconductor photocatalysis has emerged as one of the most promising approach to exploit a renewable energy source (i.e. sunlight irradiation) for several environmental purposes such as the production of clean energy (e.g. photocatalytic H2 evolution), the removal of organic and inorganic pollutants in natural water, purification of air and antibacterial activity.
In view of these recent trends, the focus of this thesis was directed towards the study of different supported photo(electro)catalytic materials for topical environmental applications:
i) Photocatalytic hydrogen gas evolution from aqueous solutions under UV light irradiation (365 nm) over highly ordered TiO2 nanotubes decorated through a sputtering/dewetting approach with a well-defined stacked co-catalyst (a WO3 layer decorated with Pt NPs);
ii) Photocatalytic hydrogen gas evolution from aqueous solutions under UV light irradiation (365 nm) over highly ordered TiO2 nanotubes decorated through a sputtering/dewetting approach with dewetted-alloyed NiCu nanoparticles;
iii) Photocatalytic reduction/scavenging of inorganic mercury (Hg(II)) from water under solar light irradiation over templated-dewetted Au on TiO2 nanotubes;
iv) Photoelectrocatalytic oxidation/abatement of inorganic arsenic (As(III)) over hematite-based photoanodes under solar light irradiation.
After a general introduction about photocatalytic processes and materials, each chapter of this dissertation contains the outcomes of the above listed studies
Fluids at interfaces: Casimir effect, depletion and thermo-osmosis.
No full textThe critical Casimir effect is the long-range interaction between two planar walls in a critical fluid due to the confinement, achieved by the wall interfaces, of the critical density fluctuations. In this Thesis we provide a microscopic description of the critical Casimir force, introducing a novel density functional approximation coupled to the hierarchical reference theory of fluids.
The depletion interaction is an effective attractive force arising between colloidal particles immersed in a solvent: The first prediction of this effect dates back to the seminal work by Asakura and Oosawa and has been obtained assuming that the colloidal particles were perfectly smooth spheres immersed in an ideal gas. In this Thesis we address the study of the interaction potential mediated by an ideal gas between two rough colloidal particles, as a function of the geometry, the dimension and the spatial configuration of the corrugations.
When a thermal gradient is applied to a fluid at contact with a surface a stationary flow develops. This effect, referred to as thermo-osmosis, has been discovered in the late nineteenth century but successful theoretical descriptions have been up to now devised only when the fluid is a rarefied gas. In this thesis we presents a microscopic theory of thermo-osmosis based on a generalisation of linear response theory to inhomogeneous and anisotropic environments and to thermal disturbances
Molecular characterization of a Mecp2Y120D mouse model and MeCP2 role in primary cilia formation: implications in Rett syndrome
No full textRett syndrome (RTT) is a neurological progressive disorder affecting about 1/10,000 new born females. Most cases of “classic” RTT are primarily ascribable to sporadic mutations in the X-linked MECP2 gene, encoding the multifunctional methyl-CpG-binding protein 2 (MeCP2). Studies of different mouse models of Mecp2 indicate that MeCP2 activities are modulated by a series of post-translational modifications.
We generated a knockin mouse model harboring the human pathogenic tyrosine 120aspartic acid (Y120D) mutation in Mecp2. This mutation was found in a female patient affected by RTT. Studies carried out on Mecp2Y120D mouse line showed a surprisingly severe phenotype overlapping that of Mecp2 null mice. The obtained data showed that the Y120D mutation causes a significant reduction in protein levels of Mecp2 and a clear defect in its chromatin binding. Since our studies on tyrosine 120 phosphorylation allowed us to functionally connect MeCP2 with the centrosome, we investigated whether Mecp2 deficiency might lead to centrosomal dysfunctions also in neurons that represent the most affected cells in RTT. Thus, we undertook a study to determine whether MeCP2 is required for the proper formation of the primary cilium. Our studies demonstrate that loss of MeCP2 determines a defect in ciliogenesis in all tested cells including murine neurons and astrocytes and RTT patients’ fibroblasts. We have also observed a functional defect in the activation of the Sonic Hedgehog pathway. Both morphological and functional defects are rescued by the stabilization of microtubules with an histone deacetylase 6 inhibitor
Development of saporin-based therapeutic options for the treatment of solid tumors.
No full textUp to now, cancer represents one of the most challenging disease to treat, mostly due to its ability to adapt and negatively respond to current available therapies. Over the past 30 years, Ribosome Inactivating Proteins (RIPs) have attracted great interest in the scientific community for their therapeutic potential. Indeed, such toxins have been extensively used as potent and versatile therapeutic weapons due to important advantages compared to chemotherapeutics: for instance, they act independently form cell cycle, killing both quiescent and dividing cells, limiting the development of cancer resistance. However, the successful application of toxins-based therapeutics to solid tumors remains to be demonstrated. In this study, we explored the potential use of the plant-RIP saporin (SAP) for the treatment of solid tumors. In particular, we propose two different strategies, in which SAP is selectively and safely conveyed to malignant cells either in the form of recombinant protein through genetically fused targeting moieties, or throughout cell-derived extracellular vesicles as vehicles. Overall our data indicate that SAP-based recombinant proteins are promising antitumoral therapeutic options. Applied as single or combined treatment, as well as used together with traditional therapeutics, they appropriately address both intra and inter- tumor heterogeneity. In addition, the use of exosomes as SAP nanocarriers is a promising strategy to improve safety and drug delivery to tumor cells
Unravelling the physiopathological role of sacsin, the protein mutated in the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
No full textSacsin is a large, multimodular protein encoded by the SACS gene and found only in vertebrates. It is expressed in the central nervous system, especially in Purkinje cells and corticospinal neurons. Bioinformatics’ predictions suggest that sacsin plays a role in protein quality control. However, to date sacsin physiological functions and subcellular localization are still open questions.
Loss of function mutations in SACS gene cause Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), an early-onset neurodegenerative disorder. Being sacsin function still unknown, the molecular pathogenesis leading to ARSACS has very poorly been investigated. My thesis is focused on exploring sacsin physiopathological role at the cellular level and on dissecting the pathogenesis of ARSACS.
First, we examined how sacsin mutations alter the residual amount of the protein in ARSACS patient cells, since until now it has never been evaluated, leaving a hole in the genotypephenotype correlation in ARSACS.
At the same time, we investigated the effects of the lack of sacsin in different models depleted of its expression (ARSACS patient fibroblasts, SACS KO HeLa cells, Sacs KO mouse embryonic fibroblasts, and primary Purkinje neurons from the Sacs KO mouse model). We found alterations in mitochondrial dynamics, namely mitochondrial hyperfusion and, by dissecting the molecular mechanism, we demonstrated that the mitochondrial fission process was indeed impaired. In line with these results, we showed that mitochondrial hyperfusion has a strong impact on mitochondrial trafficking in primary Purkinje cells that lack sacsin expression. This highlights the importance of this phenotype in the pathogenesis of ARSACS, as Purkinje neurons are the first cells to be affected.
In sacsin-depleted cells, we detected a dramatic remodelling of the cytoskeletal network, particularly of intermediate filaments. Our data supports the hypothesis that sacsin may be involved in intermediate filament remodelling in an indirect manner, such as by regulating their folding. This is also suggested by the predicted chaperone-like activities of certain sacsin domains. An intermediate filament reorganization and/or accumulation could sterically hinder both transport and distribution of mitochondria in Purkinje neurons of Sacs KO mouse. On the other hand, cytoskeletal derangement could be responsible for impairing DRP1 recruitment.
The cellular phenotypes that we have identified in the absence of sacsin are steps forward in understanding the pathogenetic cascade of ARSACS and shed light on potential sacsin functions
Per una storia della comunicazione globale: dal Centro Mondiale di Andersen al Web.
No full textThe concept of global communication was defined through the comparison between the World Centre of Communication and the World Wide Web. This notion refers to the idea, spread in the nineteenth century, to create a system which ensure connection over long distances. Electrification, the construction of infrastructures and the use of media allowed to connect geographically distant places. This process, which began in the 19th century, ended its long and difficult path between the 80s and 90s of the 20th century with the advent of the World Wide Web. Well before Tim Berners Lee’s innovation, Norwegian sculptor Hendrik Christian Andersen developed an ideal project with similar objectives: The World Centre of Communication. Poorly studied by historiography in the field of technology and communication, this plan represented the hypothesis to create a universal communication system to connect different territories and spread information and knowledge throughout the globe. Unfortunately, this idea remained a utopia; while the Web has developed between the 80s and 90s of the twentieth century, becoming a real universal library of information open and accessible. Over time Lee’s innovation has gone into crisis. The digital giants have taken control of the network: through the algorithms - complex, opaque and invisible -, they have undermined the pedagogical and educational functions of the Web, supporting a commercial orientation
Privacy nell’era digitale: la tutela dei dati personali fra legislazione e salvaguardia della libertà e dignità dell’uomo
No full textIn the first chapter, starting from some general definitions of privacy and tracing the history of the term since its modern affirmation, we have directed our attention to the inherent aspect of the protection of personal data, coming to outline the concept of privacy as "self-ownership ", an area belonging to the subject and, as such, like any economic asset (although it is an immaterial property) needs to be safeguarded from external interference. From the question of privacy and its protection, the foundations have been laid for a broader reflection, closely related to the values of human dignity and freedom, fundamental and essential components of every democracy.
In the second chapter we focused on the description of the complex social reality in which we live: postmodernity. Our analysis took into consideration three closely related aspects: 1. Technological aspect: it was highlighted how a radical anthropological change occurred in human being following an instrumental dimension that influenced his mindset (brainframe) allowing him to transcend the categories of space and time, virtually extending his being beyond the physicality of the body. 2. Socio-economic aspect: we have shown how the emergence of a new planetary economy has favored the birth of a morphological structure of the society of which the Network embodies the model par excellence. 3. Political aspect: the establishment of forms of power and control that tend to colonize every aspect of life in a subliminal way.
In the third chapter, starting from the concept of the infosphere, the economic, political and social value of the big data (Big data) and the dangers that may derive from their mismanagement by third parts or from their voluntary dissemination have been highlighted, as in the case of social networks.
In the fourth chapter the general legal principles underlying the right to privacy have been reported. Moving from a broader context, which sees the protection of the private life of the person sanctioned for the first time in 1948 with the Universal Declaration of Human Rights, we have restricted the field of investigation to the right to the protection of personal data, analyzing in the specific the most interesting points of the new General Data Protection Regulation (GDPR).
In the fifth and last chapter, we focused on what, hopefully, should be the direction to take to protect the person in the digital age and guarantee them the rights of freedom and dignity; it provides, in addition to solid legislation on data protection (a necessary but not sufficient condition), a cultural-educational policy aimed at making the individual acquire conscious digital citizenship
Inibitori PCSK-9 e infiammazione in pazienti ad alto richio cardiovascolare
No full textInibitori PCSK-9 e infiammazione in pazienti ad alto rischio cardiovascolare Inflammation plays an important role in atherosclerosis both in the early stage and in its progression.
PCSK-9 is a newly discovered serine protease playing a key role in destroying LDL receptors in liver and thereby controlling the level of LDL in plasma. New monoclonal antibodies capable of binding to PCSK 9 and blocking their interaction with hepatic receptors for LDL were therefore developed.
NETs are one of the most recent inflammatory markers used for atherosclerotic vasal damage.
The aim of this study is to evaluate the inflammatory response of dyslipidemic patients at high nontarget cardiovascular risk which have been treated with PCSK9 inhibitors in association with statin and compared it to the inflammatory response of a group of patients treated with statin therapy only.
The data of our research is taken from a group of 19 patients with high-risk cardio-vascular dyslipidemia. Among these, 13 patients had non-target LDL levels with the highest tolerated statin dose and were treated with statin and PCSK9; while 6 patients had target LDL values with statin
therapy alone.
Anthropometric measurements such as blood chemistry tests, quantification of NETs formation in neutrophil and its correlation with the elastase release and detecting of some cytokines (IL8 IL10 IL17 IL-1beta and TNFalfa) were determined in all patients.
In conclusion in patients already treated with maximal statin doses, it seems that the addition of PCSK9i did not affect the ability of neutrophils to release NETs nor the trend over time of the inflammatory cytokines evaluated. We assume that the inflammatory pattern may have already been intensively modified by statin therapy at high dosages