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Hybrid Nano-systems Based on PEGylate Porphyrins: Synthesis, Characterization and Theranostic Applications
No full textFollowing the modern lines of development in theranostic field, this PhD research project focuses mainly on the field of oncological therapies where the primary purpose of the research is to increase the effectiveness of treatments and to decrease the undesirable toxic side effects of current therapies, which indiscriminately affect both sick and healthy cells, causing often serious collateral damages.
The goal can be achieved by creating biocompatible smart systems that do not require carriers to function, but that are themselves able to "move" recognize and treat diseased tissues. The research project proposes the development of new organic/inorganic hybrid nanosystems having a core-shell-shell structure, consisting of nanoparticles (NPs) (Au and/or Fe3O4@Au) in which PEGylate porphyrin systems are bounded. The choice of synthesizing these hybrid systems, stems from the possibility of exploiting the different properties of the individual components, combined into a single complex system. The gold nanoparticles were chosen for the different properties in the theranostic field. AuNPs are considered to be relatively biologically non-reactive and therefore suitable for in vivo applications. Other advantageous qualities include the strong optical properties of AuNPs due to localized surface plasmon resonance (LSPR), easily controllable surface chemistry which enables versatility in adding surface functional groups, and lastly, the ease in control over particle size and shape during synthesis. Silver nanoparticles (AgNPs) are increasingly being investigated as tools for novel cancer therapeutics, capitalizing on their unique properties to enhance potential therapeutic efficacy. The AgNPs are a promising tool as anticancer agents in diagnostics and probing, with strong effects against different cancer cell lines offering many advantages. Their better penetration, and the possibility to track AgNPs in the body make them a more efficient tool in cancer treatment with less risk compared to standard therapeutic procedures. The unique AgNP properties, such as easy surface functionalization, optical properties, reproducible synthetic routes and high surface: volume ratio, makes them suitable for cancer treatment. The optical properties can be tuned to have an absorption at specific wavelengths that is useful for imaging and photothermal applications in tissue. The magnetite core will provide the paramagnetic properties necessary for use in the Targeted Drug Delivery (NPs tissues via magnetic field), in Magnetic Resonance Imaging and Magnetic Hyperthermia (the magnetic NPs may be subjected to an alternating magnetic field, overheating and thus determining cell death). The nanoscale dimensions of the complex system (40-100 nm) will allow the latter to perform passive targeting (EPR effect), while the external shell obtained by functionalization with the PEGylated porphyrins derivatives will induce the necessary water solubility and biocompatibility of the whole system. Given the excellent absorption spectroscopic properties, fluorescence (to monitor its presence inside the tissues) and photo-cytotoxicity (for the photodynamic therapy of tumors), it will be possible to strongly implement the field of application and efficiency of these nanohybrid systems. In synthesis, upon validation of the functioning of the system, the synthesis strategy can be adapted to functionalize and/or co-functionalize the nanoparticles also with active targeting agents to limit the accumulation exclusively in diseased tissues endowed with specific receptors, further implementing the targeting properties described above. Therefore, the results obtained during my PhD research work, could be a fundamental starting point in order to developing systems for theranostic applications, exploiting both the nanoparticles and the porphyrin derivatives properties, thus to obtain multifunctional platforms for biomedical applications
Modulation of neuroplasticity in humans after acute intake of antidepressant, anxiolytic and adaptogenic herbs
No full textHerbal medicine represents one of the most frequently used complementary and alternative approaches for the treatment of psychiatric conditions such as depression, anxiety and sleep disturbance. Among the most used herbal medicines, Hypericum perforatum (HYP) extract, Valeriana officinalis extract (VE) and Rhodiola rosea extract (RRE) are the oldest and most thoroughly researched phytotherapeutic medications. Despite their widespread use, the mechanisms of action and the role of the different compounds of these herbal products are still a matter of debate and warrant the need to develop new approaches to investigate their effects in humans. Noninvasive brain stimulation protocols, such as Transcranial Magnetic Stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) can be used to elucidate the mechanisms of action of psychoactive substances at the cortical level in humans. TMS can be used to test the affect of acute drug intake at the system level in the cerebral cortex in humans. Pharmaco-TMS offers a broad array of measures of cortical excitability and offers the possibility to probe the activity of different forms of inhibitory and excitatory networks. Furthermore, tDCS is a safe noninvasive brain stimulation technique that, combined with TMS, has been shown to induce cortical plastic changes in humans that resemble Long-term potentiation and depression (LTP and LTD)-like plasticity. The studies presented in this thesis explored the neurophysiological effect of the acute intake of herbal products commonly used to treat psychiatric conditions. Study 1 explored the effect of HYP extract acute dose intake on cortical excitability and plasticity. The results indicated that HYP acute intake affected cortical plasticity induced by cathodal tDCS by modulating LTD-like plasticity in a similar manner of conventional antidepressants. Study 2 investigated the effects of a single dose intake of VE on cortical excitability. It was found that VE intake modulated intracortical facilitatory circuits explored by TMS. Study 3 studied the effect of a single oral dose of RRE intake on cortical excitability and plasticity. Results showed that RRE acute intake prevented cathodal tDCS-induced LTD and increased (non-significantly) LTP-like plasticity. The translational studies described in the thesis add to the understanding of how the herbal products used in psychiatry can affect brain circuitries in humans
Scene Understanding for Parking Spaces Management
No full textThe major part of world-wide population moved to urban areas. After such process many issues of major cities have worsened, e.g. air pollution, traffic, security. The increase of security cameras and the improvements of Computer Vision algorithm can be a good solution for many of those problems.
The work in this thesis was started after a grant by Park Smart s.r.l., a company located in Catania, which believes that Computer Vision can be the answer for parking space management.
The main problem the company has to face is to find a fast way to deploy working solutions, lowering the labeling effort to the minimum, across different scene, cities, parking areas.
During the three years of doctoral studies we have tried to solve the problem through the use of various methods such as Semi-Supervised Learning, Counting and Scene Adaptation
through Image Classification, Object Detection and Semantic Segmentation.
Semi-Supervised classification was the first approach used to decrease labeling effort for fast deployment. Methods based on counting objects, like cars and parking spots, were analyzed as second solution. To gain full knowledge of the scene we focused on Semantic Segmentation and the use of Generative Adversarial Networks in order to find a viable way to reach good Scene Adaptation results comparable to state-of-the-art methods
K*(892)± resonance with the ALICE detector at LHC
No full textK*(892)± resonance with the ALICE detector at LHC
Author: Kunal Garg
PhD Cycle XXXI, University of Catania
It has been established that ultra-relativistic heavy-ion collisions produce a hot and dense QCD system which behaves like a perfect fluid. The study of the Quark Gluon Plasma created in these collisions is important to understand the cosmic evolution of our Universe. The study of strange hadronic resonances in pp collisions contributes to the study of strangeness production in small systems. Usually, measurements in pp collisions constitute a reference for the study in larger colliding systems and provide constraints for tuning QCD-inspired event generators and then to test specific aspects of QCD in the non-perturbative sector. However recent observations at the LHC have shown striking similarities between Pb-Pb collisions and high-multiplicity p-Pb and pp collisions. In the elementary collisions a large variation of the characteristics of the event and of the strange particle production rate has been observed as a function of the charged particle multiplicity density. In particular it has been observed as particle production depends only from the event multiplicity and it is independent of the system size and collision energy.
This thesis reports about first measurement of K^{*}(892)^{\pm} in pp collisions at \sqrt{s} = 13 TeV in inelastic pp collisions and in different charged particle multiplicity classes. In particular the transverse momentum (p_{T}) spectrum, the integrated yield, the mean p_{T} and the ratio to stable hadrons as pions and kaons have been measured. Moreover the K^{*}(892)^{0} p_{T} spectrum in inelastic pp collisions at the same energy has been also measured. Similar results have been obtained for charged and neutral K^{*}. The K*(892)± p_{T} spectrum has been compared to the predictions of some event generators as PYTHIA6, PYTHIA8 and EPOS-LHC. Furthermore, the comparison of the p_{T} spectrum with the one obtained at different energies has shown a hardening of the spectra with increasing energy of the collisions.
Increase of the K*(892)± yield and mean p_{T} when growing the event multiplicity, confirms the independence of the particle yields from the collision system or energy. From the distribution of the K^{*}/K ratio as a function of the charged particle multiplicity, a hint of suppression of the K* production has been observed in high multiplicity pp collisions. This in an analogy to the K^{*}/K results in heavy-ion collisions, is consistent with the presence of re-scattering effects in an hadronic phase in high multiplicity pp collisions
The role of VIP family members in diabetic retinopathy
No full textDiabetic retinopathy (DR) is a microvascular complication of diabetes leading to blindness. Hyperglycemic/hypoxic microenvironment concurs to mechanical breakdown of blood-retinal barrier (BRB) as well as the aberrant angiogenesis activating many downstream target genes including inflammatory cytokines and vasoactive peptides, such as interleukin-1beta and vascular endothelial growth factor (VEGF). To date, intravitreal injection of agents directed against VEGF represents the elective DR therapy. However, they counteract efficaciently ocular neovascularization only in 50% of treated patients, suggesting that other pathogenic events may play an important role in non-responders. Therefore, there is an increased need for new molecule able to counteract microenvironmental alterations of DR.
It has been largely demonstrated that pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective effect against retinal injuries, including DR. However, until now, no study has investigated their protective role against the harmful combined effect of both hyperglycemia and hypoxia.
The main objectives of this PhD thesis have been evaluate whether PACAP protects retinal tissue of diabetic rats through modulation of hypoxia and inflammation, both converging on angiogenic process. Moreover, we have investigated the protective effects of PACAP and VIP on BRB integrity whose breakdown due to hypoxic and inflammatory event, leads to diabetic macular edema (DME).
The results have demonstrated that a single intravitreal administration of PACAP in streptozotocin-injected rats modulated the expression of hypoxic, inflammatory and angiogenic factors. Moreover, PACAP and VIP restored the integrity of BRB through the activation of phosphoinositide 3 kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) survival signaling pathways.
Overall, these data indicate that these peptides, both in vivo and in vitro, perform a beneficial effect to attenuate some pathologic events occuring in DR
Torri campanarie degli edifici ecclesiastici tradizionali allo specchio tra conoscenza e sicurezza. Tecnologia e forma negli areali a rischio della Sicilia orientale e della Castilla y León
No full textLe torri campanarie di fattura tradizionale contrassegnano i centri storici europei, rappresentando l emblema del paesaggio urbano e il simbolo di identità per la popolazione. A causa della spiccata verticalità, queste emergenze architettoniche sono sempre esposte a rischi di diversa natura che ne minacciano la sopravvivenza. Nel campo del restauro e della conservazione di questi edifici è fondamentale la conoscenza preventiva dei caratteri geometrici e tecnico costruttivi per potere intervenire in modo da garantire sia la tutela del valore culturale sia la messa in sicurezza. In ragione di ciò, la presente ricerca, scegliendo due areali geograficamente distanti ed esposti a rischi differenti come la Sicilia orientale e la Castilla y Leòn, vuole studiare le configurazioni geometriche e le tecniche costruttive di questi edifici al variare del rischio prevalente.
In Sicilia lo studio ha approfondito il tema delle torri campanarie nell areale Etneo, zona esposta da sempre a rischio sismico e vulcanico. È stato condotto un censimento dei campanili in muratura esistenti mai effettuato precedentemente e una classificazione tipologica, seguendo le categorie proposte dagli studi di tipo empirico sugli edifici ecclesiastici storici soggetti a rischio sismico. Successivamente, sono stati selezionati alcuni casi studio ritenuti emblematici per l areale (risalenti ai secoli XVII e XVIII) e che sono stati studiati più approfonditamente anche grazie a rilievi di tipo diretto e fotogrammetrico, sia per individuare le configurazioni geometriche e le tecniche costruttive più ricorrenti sia le possibili criticità intrinseche celate in esse. In questo modo possono essere individuati degli indicatori di vulnerabilità, come richiesto anche dalle norme italiane sugli studi preventivi alle valutazioni di vulnerabilità sismica.
In Castilla y Leòn sono stati selezionati alcuni casi studi emblematici per l areale della Tierra de Campos, territorio a rischio idrogeologico a causa dei continui fenomeni di ritiro e rigonfiamento del terreno argilloso. I casi analizzati, studiati con rilievi diretti e fotogrammetrici, risalgono ai secoli XVI e XVII e sono contraddistinti da stati di conservazione differenti (soprattutto allo stato di rudere). Lo studio delle configurazioni geometriche e delle tecniche costruttive rivelano come il rischio che realmente minaccia queste architetture è il rischio di obsolescenza naturale a causa dello spopolamento dei piccoli centri e la conseguente assenza di manutenzione.
In conclusione, la ricerca ha evidenziato come tali fabbriche in Sicilia convivano da sempre con il rischio sismico e per tale ragione, seguendo la regola dell arte, geometrie, materiali e tecniche contribuiscono alla sopravvivenza degli edifici (tranne in caso di eventi sismici di carattere distruttivo). In Castilla y León invece le torri campanarie tradizionali risultano non solo vulnerabili ai fenomeni idrogeologici del territorio ma anche, e soprattutto, ai fenomeni di deterioramento per obsolescenza che purtroppo non lascia possibilità di sopravvivenza in assenza di continui monitoraggi e manutenzione
Synthesis of hybrid metalorganic/inorganic systems and doped halide thin films for photovoltaics
No full textThe aim of the present PhD thesis has been the synthesis of novel materials for photovoltaic (PV) technologies. One possible way to increase the conversion efficiency of silicon solar cells is to shift the incident sunlight spectrum, converting photons poorly exploited by the active PV material into more effective photons. The materials studied as energy converters, consist of thin film layers integrated in the PV panel and made of a host material and an active luminescent species. In the present thesis, the energy conversion systems made of lanthanide doped fluorides (CaF2, NaYF4, NaGdF4, KYF4 and YOF) have been synthetized using MOCVD and sol-gel methods and deeply studied for their potential integration in silicon solar cells. Together with the traditional silicon PV technology, a new class of PV materials, based on inorganic multi-junction technology, new hybrid materials and organic dye-sensitized solar cells (DSSC) is subject of interest in the last years. Hybrid metalorganic/inorganic systems of Eu-complex/NiO films have been developed for the DSSC technology and for the potential improvement of the PV material with new functionalities, that combine the semiconductor behavior of the inorganic part to the luminescent properties of the metalorganic component. The all-inorganic halide perovskite CsPbBr3 has been synthetized through a precipitation method. The perovskite CsPbBr3 has a semiconductor behavior, with an energy band gap useful in the PV application and has the advantages to not have any labile or expensive organic components
Towards the post-antibiotic era: The role of antibiotic resistant enterococci in different sources
No full textL esplosione del fenomeno dell antibiotico resistenza (AR) si configura come un fenomeno globale. Sebbene i batteri AR sia stati per lungo tempo esclusivamente associati ad ambienti ospedalieri e/o sanitari, nell ultimo decennio sono stati isolati sempre più frequentemente, in numerosi altri ambienti e persino negli alimenti. La diffusione dell antibiotico resistenza tra gli enterococchi, noti come patogeni nosocomiali, ha contribuito a innalzarne il rischio di colonizzazione e infezione, incrementandone l importanza clinica.
L'obiettivo principale della presente tesi di dottorato è stato quello di indagare la presenza e la struttura della popolazione enterococcica AR sia in matrici alimentari sia ambientali. In dettaglio, sono stati presi in considerazione due formaggi siciliani (Capitolo 1) e un impianto di depurazione urbano (Capitolo 2). Ad oggi, questa rappresenta la prima evidenza scientifica di AR in enterococchi isolati da formaggio Ragusano DOP e da un impianto di trattamento delle acque reflue urbane siciliano. I risultati ottenuti dal formaggio hanno evidenziato la presenza di una specifica popolazione, per lo più riferita alla specie E. durans, per la quale meno informazioni sull AR sono disponibili in letteratura. In particolare, è stata rilevata un elevata prevalenza di multi-resistenza e alcuni ceppi hanno evidenziato resistenza alla vancomicina. Inoltre, la distribuzione multimodale dei valori di MIC, all interno della specie, ha consentito la distinzione di due sottopopolazioni, suggerendo meccanismi di acquisizione genica di AR.
Per quanto riguarda gli enterococchi isolati dal sistema di depurazione di acque urbane, i risultati hanno evidenziato la dominanza di E. faecium in tutti i siti analizzati e un'alta prevalenza di AR nei riguardi di numerosi antibiotici. Attraverso l analisi PFGE numerosi profili unici sono stati ottenuti e la presenza dello stesso clone con differenti profili di resistenza, in differenti siti, è stata osservata. In conclusione, i risultati ottenuti rafforzano la necessità di un monitoraggio costante e di una sorveglianza attiva sulla presenza di enterococchi AR sia nei formaggi che in ambienti acquatici, al fine di contenere il rischio per la salute umana
Impact of Vitamin D intake and high-fat diets on liver and muscle: a rat model of Western and Mediterranean Diets
No full textBackground: The metabolic syndrome is associated with sarcopenia. Decreased serum levels of Vitamin D (VitD) and insulin-like growth factor (IGF)-1 and their mutual relationship were also reported. We aimed to evaluate whether different dietary profiles, containing or not VitD, may exert different effects on muscle and liver.
Methods: Twenty-eight male rats were fed for 10 weeks in order to detect early defects induced by different dietary regimens: regular diet (R); regular diet with vitamin D supplementation (R-DS) and regular diet with vitamin D restriction (R-DR); high-fat butter-based diets (HFB-DS and HFB-DR) with 41% energy from fat; high-fat extra-virgin olive oil-based diets (HFEVO-DS and HFEVO-DR) with 41% energy from fat. IL-1beta, insulin-like growth factor (IGF)1, Dickkopf-1 (DKK-1), and VitD-receptor (VDR) expressions were evaluated by immunohistochemistry in both muscle and liver, Collagen type I expression was evaluated in the liver. Muscle fiber perimeter was measured by histology and morphometric analysis. Severity of NAFLD was assessed by NAFLD Activity Score (NAS).
Results: Muscle fibers of HEVO-DS rats were hypertrophic, comparable to those of the R-DS rats. An inverse correlation existed between the dietary fat content and the perimeter of the muscle fibers (p < 0.01). In HFB-DR rats, muscle fibers appeared hypotrophic with an increase of IL-1beta and a dramatic decrease of IGF-1 expression. All liver samples showed a NAS between 0 and 2 considered not diagnostic of steatohepatitis. Collagen I, although weakly expressed, was statistically greater in HFB-DS and HFB-DR groups. IL-1beta was mostly expressed in rats fed by HFBs and HFEVOs and R-DR, and almost absent in R and R-DS diets. IGF-1 and DKK-1 were reduced in HFBs and HFEVOs diets and in particular in DR groups.
Conclusions: High-fat western diet could impair muscle and damage liver tissue in terms of inflammation and collagen I deposition, putting the basis for the subsequent steatohepatitis, still not identifiable histopathologically. VitD associated with a Mediterranean diet showed trophic action on the muscle fibers. Vitamin D restriction increases inflammation and reduces the expression of IGF-1 in the liver, worsening the fat-induced changing. EVO seems be protective against liver collagen I production
Arf good semigroups
No full textIn this thesis we explore the properties of the Arf good subsemigroups of
N^r, with
r>1. We give a way to compute all the Arf semigroups with a given collection of multiplicity branches. We also deal with the problem of determining the Arf closure of a set of vectors and of a good semigroup, extending the concept of characters of an Arf numerical semigroup to Arf good semigroups. Furthermore we present some procedures to calculate the set of the Arf good semigroups with a given conductor and with a given genus. Finally we give an effcient algorithm for the computation of the Arf Closure of an algebroid curve with more than one branch