Glycomics as an innovative technology to identify biomarkers of aging

Introduction. Glycomic analysis allows investigating on the global glycome within body fluids (as serum/plasma), this could eventually lead to identify new types of disease biomarkers, or as in this study, biomarkers of human aging studying specific aging models. Recent studies demonstrated that the plasma N-glycome is modified during human aging, suggesting that measurements of log-ratio of two serum/plasma N-glycans (NGA2F and NA2F), named GlycoAge test could provide a non-invasive biomarker of aging. Down syndrome (DS) is a genetic disorder in which multiple major aspects of senescent phenotype occur much earlier than in healthy age-matched subjects and has been often defined as an accelerated aging syndrome. The aim of this study was to compare plasma N-glycome of patients affected by DS with age- and sex matched non-affected controls, represented by their siblings (DSS), in order to assess if DS is characterized by a specific N-glycomic pattern. Therefore, in order to investigate if N-glycans changes that occur in DS were able to reveal an accelerated aging in DS patients, we enrolled the mothers (DSM) of the DS and DSS, representing the non-affected control group with a different chronological age respect to DS. We applied two different N-glycomics approaches on the same samples: first, in order to study the complete plasma N-glycome we applied a new high-sensitive protocol based on a MALDI-TOF-MS approach, second, we used DSA-FACE technology. Results: MALDI-TOF/MS analysis detected a specific N-glycomics signature for DS, characterized by an increase of fucosylated and bisecting species. Moreover, in DS the abundance of agalactosylated (as NA2F) species was similar or higher than their mothers. The measurement of GlycoAge test with DSA-FACE, validated also by MALDI-TOF, demonstrated a strongly association with age, moreover in DS, it’s value was similar to their mothers, and significantly higher than their age- and sex matched not-affected siblings

Development of innovative catalysts for the hydrodechlorination to fluoroethers

In this work the hydrodechlorination of CF3OCFClCF2Cl to produce unsaturated CF3OCF=CF2 was studied over a series of supported metal catalysts. Currently this molecule is produced from the precursor CF3OCFClCF2Cl by dechlorination with zinc powder. An important cost on the economic and environmental balance is represents by the large amount of ZnCl2 produced and to be disposed of. A new approach, based on gas-phase hydrodechlorination over supported catalysts can lead to a new sustainable process. During the feasibility step of this project, substantially two kind of materials were studied: metals supported over activated carbon and Pd/Cu species supported over MCM-41 mesoporous silica. Observed catalytic performances were strongly dependent on the metal and support used. All carbon-supported Ru, Pd, and bimetallic catalysts are fairly active and yielded the target product CF3OCF=CF2, the higher selectivity being obtained with ruthenium- and palladium-based materials. Nevertheless, Ru-based catalysts showed poor stability and this deactivation may be attributed to the deposition of chlorinated organic species blocking the active sites. On the other hand, palladium-containing catalysts showed high stability. Ru/Pd and Pd/Cu bimetallic catalysts exhibited long-term selectivity and stability, highlighting the possibility for these materials to be employed in the CF3OCF=CF2 production process. During the second part of this thesis, a series of bimetallic meso-structured Pd/Cu MCM-41 catalysts were studies to overcome possible mass transfer limitations. The materials were obtained by different synthesis methods. The incorporation of Pd and Cu during MCM-41 synthesis, did not destroy the typical hexagonal array and ordered pore system of MCM-41. However, the calcination for the removal of the template provoked significant segregation of oxides. The impregnation leads to pore-occlusion and formation of Cu particles and large bimetallic PdCu species. Larger metal particles leads to lower CF3OCFClCF2Cl conversion, while the monometallic particles can decrease the selectivity to CF3OCF=CF2, fostering the dehalogenation to CF3OCH=CF2.

Design and experimental characterization of antennas and wireless systems for innovative wearable and implantable ultra low–power applications

The present PhD thesis exploits the design skills I have been improving since my master thesis’ research. A brief description of the chapters’ content follows. Chapter 1: the simulation of a complete front–end is a very complex problem and, in particular, is the basis upon which the prediction of the overall performance of the system is possible. By means of a commercial EM simulation tool and a rigorous nonlinear/EM circuit co–simulation based on the Reciprocity Theorem, the above–mentioned prediction can be achieved and exploited for wireless links characterization. This will represent the theoretical basics of the entire present thesis and will be supported by two RF applications. Chapter 2: an extensive dissertation about Magneto–Dielectric (MD) materials will be presented, together with their peculiar characteristics as substrates for antenna miniaturization purposes. A designed and tested device for RF on–body applications will be described in detail. Finally, future research will be discussed. Chapter 3: this chapter will deal with the issue regarding the exploitation of renewable energy sources for low–energy consumption devices. Hence the problem related to the so–called energy harvesting will be tackled and a first attempt to deploy THz solar energy in an innovative way will be presented and discussed. Future research will be proposed as well. Chapter 4: graphene is a very promising material for devices to be exploited in the RF and THz frequency range for a wide range of engineering applications, including those ones marked as the main research goal of the present thesis. This chapter will present the results obtained during my research period at the National Institute for Research and Development in Microtechnologies (IMT) in Bucharest, Romania. It will concern the design and manufacturing of antennas and diodes made in graphene–based technology for detection/rectification purposes.

Scripting automation e modelli bayesiani: Applicazioni cliniche in radioterapia e sviluppo di tecniche innovative per adaptive radiation therapy

La presente ricerca consiste nel validare ed automatizzare metodiche di Adaptive Radiation Therapy (ART), che hanno come obiettivo la personalizzazione continua del piano di trattamento radioterapico in base alle variazioni anatomiche e dosimetriche del paziente. Tali variazioni (casuali e/o sistematiche) sono identificabili mediante l’utilizzo dell’imaging diagnostico. Il lavoro svolto presso la struttura di Fisica Medica dell’Azienda Ospedaliera Universitaria del Policlinico di Modena, si inserisce in un progetto del Ministero della Salute del bando Giovani Ricercatori dal titolo: “Dose warping methods for IGRT and ADAPTIVERT: dose accumulation based on organ motion and anatomical variations of the patients during radiation therapy treatments”. Questa metodica si sta affermando sempre più come nuova opportunità di trattamento e, per tale motivo, nasce l’esigenza di studiare e automatizzare processi realizzabili nella pratica clinica, con un utilizzo limitato di risorse. Si sono sviluppati script che hanno permesso l’automazione delle operazioni di Adaptive e deformazioni, raccogliendo i dati di 51 pazienti sottoposti a terapia mediante Tomotherapy. L’analisi delle co-registrazioni deformabili delle strutture e delle dosi distribuite, ha evidenziato criticità del software che hanno reso necessario lo sviluppo di sistemi di controllo dei risultati, per facilitare l’utente nella revisione quotidiana dei casi clinici. La letteratura riporta un numero piuttosto limitato di esperienze sulla validazione e utilizzo su larga scala di questi tools, per tale motivo, si è condotto un esame approfondito della qualità degli algoritmi elastici e la valutazione clinica in collaborazione di fisici medici e medici radioterapisti. Sono inoltre stati sviluppati principi di strutturazione di reti Bayesiane, che consentono di predirre la qualità delle deformazioni in diversi ambiti clinici (H&N, Prostata, Polmoni) e coordinare il lavoro quotidiano dei professionisti, identificando i pazienti, per i quali sono apprezzabili variazioni morfo-dosimetriche significative. Da notare come tale attività venga sviluppata automaticamente durante le ore notturne, sfruttando l’automation come strumento avanzato e indipendente dall’operatore. Infine, il forte sviluppo, negli ultimi anni della biomeccanica applicata al movimento degli organi (dimostrato dalla numerosa letteratura al riguardo), ha avuto come effetto lo sviluppo, la valutazione e l’introduzione di algoritmi di deformazione efficaci. In questa direzione, nel presente lavoro, si sono analizzate quantitivamente le variazioni e gli spostamenti delle parotidi, rispetto all’inizio del trattamento, gettando le basi per una proficua linea di ricerca in ambito radioterapico.

Social inclusion of vulnerable groups through participatory and emancipatory approaches. Implementing active citizenship and socially innovative actions in the framework of civil & human rights model of disability

The research hypothesis of the thesis is that “an open participation in the co-creation of the services and environments, makes life easier for vulnerable groups”; assuming that the participatory and emancipatory approaches are processes of possible actions and changes aimed at facilitating people’s lives. The adoption of these approaches is put forward as the common denominator of social innovative practices that supporting inclusive processes allow a shift from a medical model to a civil and human rights approach to disability. The theoretical basis of this assumption finds support in many principles of Inclusive Education and the main focus of the hypothesis of research is on participation and emancipation as approaches aimed at facing emerging and existing problems related to inclusion. The framework of reference for the research is represented by the perspectives adopted by several international documents concerning policies and interventions to promote and support the leadership and participation of vulnerable groups. In the first part an in-depth analysis of the main academic publications on the central themes of the thesis has been carried out. After investigating the framework of reference, the analysis focuses on the main tools of participatory and emancipatory approaches, which are able to connect with the concepts of active citizenship and social innovation. In the second part two case studies concerning participatory and emancipatory approaches in the areas of concern are presented and analyzed as example of the improvement of inclusion, through the involvement and participation of persons with disability. The research has been developed using a holistic and interdisciplinary approach, aimed at providing a knowledge-base that fosters a shift from a situation of passivity and care towards a new scenario based on the person’s commitment in the elaboration of his/her own project of life.

Behaviour and applications of elastic waves in structures and metamaterials

The present thesis focuses on elastic waves behaviour in ordinary structures as well as in acousto-elastic metamaterials via numerical and experimental applications. After a brief introduction on the behaviour of elastic guided waves in the framework of non-destructive evaluation (NDE) and structural health monitoring (SHM) and on the study of elastic waves propagation in acousto-elastic metamaterials, dispersion curves for thin-walled beams and arbitrary cross-section waveguides are extracted via Semi-Analytical Finite Element (SAFE) methods. Thus, a novel strategy tackling signal dispersion to locate defects in irregular waveguides is proposed and numerically validated. Finally, a time-reversal and laser-vibrometry based procedure for impact location is numerically and experimentally tested. In the second part, an introduction and a brief review of the basic definitions necessary to describe acousto-elastic metamaterials is provided. A numerical approach to extract dispersion properties in such structures is highlighted. Afterwards, solid-solid and solid-fluid phononic systems are discussed via numerical applications. In particular, band structures and transmission power spectra are predicted for 1P-2D, 2P-2D and 2P-3D phononic systems. In addition, attenuation bands in the ultrasonic as well as in the sonic frequency regimes are experimentally investigated. In the experimental validation, PZTs in a pitch-catch configuration and laser vibrometric measurements are performed on a PVC phononic plate in the ultrasonic frequency range and sound insulation index is computed for a 2P-3D phononic barrier in the sonic frequency range. In both cases the numerical-experimental results comparison confirms the existence of the numerical predicted band-gaps. Finally, the feasibility of an innovative passive isolation strategy based on giant elastic metamaterials is numerically proved to be practical for civil structures. In particular, attenuation of seismic waves is demonstrated via finite elements analyses. Further, a parametric study shows that depending on the soil properties, such an earthquake-proof barrier could lead to significant reduction of the superstructure displacement.

Innovative techniques for sport turf managing: Agronomic and phyisiological implications

The growing substrate of the putting greens is considered a key factor for a healthy turf ecosystem. Actually detailed study on the effects of growth promoting bacteria and biostimulants on a professional sport turf are very limited. This thesis aimed to study the effectiveness of different microorganisms and biostimulants in order to improve the knowledge relative to the relationship between the beneficial microflora and root apparatus of sport turfs. The research project was divided in three principal steps: Initially, commercial products based on biostimulants and microorganisms were tested on a Lolium perenne L. essence grown in a controlled-environment. The principal evaluations were the study of the habitus of plants, biomass production and length of leaves and roots. Were studied the capacity of colonization of microorganisms within root tissues and rhizosphere. In the second step were developed two different biostimulant solutions based on effective microorganisms, mycorrhizae and humic acids. This test was conducted both on an Agrostis stolonifera putting green (Modena Golf & Country Club) in a semi-field condition and within a growth chamber on a Lolium perenne L. essence. Fungicide and chemicals applications were suspended in order to assess the effectiveness of the inoculants for nutrition and control of pests. In the last step, different microorganism mixes and biostimulants were tested on an experimental putting green in the Turf Research Center (TRC) (Virginia Tech, United States) in a real managing situation. The effects of different treatments were studied maintaining all chemicals and mechanicals managements scheduled during a sport season. Both growth-chamber and field results confirmed the capacity of microorganisms based biostimulants to promote the physiologic conditions of the plants, improve the growth of the roots and enhance the aesthetic performance of the turf. Molecular analysis confirmed the capacity of microorganisms to colonize the root tissues.

Sperimentazione di metodologie innovative di indagine termografica in campo industriale

La termografia è un metodo d’indagine ampiamente utilizzato nei test diagnostici non distruttivi, in quanto risulta una tecnica d’indagine completamente non invasiva, ripetibile nel tempo e applicabile in diversi settori. Attraverso tale tecnica è possibile individuare difetti superficiali e sub–superficiali, o possibili anomalie, mediante la rappresentazione della distribuzione superficiale di temperatura dell’oggetto o dell’impianto indagato. Vengono presentati i risultati di una campagna sperimentale di rilevamenti termici, volta a stabilire i miglioramenti introdotti da tecniche innovative di acquisizione termografica, quali ad esempio la super-risoluzione, valutando un caso di studio di tipo industriale. Si è effettuato un confronto tra gli scatti registrati, per riuscire a individuare e apprezzare le eventuali differenze tra le diverse modalità di acquisizione adottate. L’analisi dei risultati mostra inoltre come l’utilizzo dei dispositivi di acquisizione termografica in modalità super-resolution sia possibile anche su cavalletto.

Innovative Man Machine Interfaces In Aeronautics

The research activity focused on the study, design and evaluation of innovative human-machine interfaces based on virtual three-dimensional environments. It is based on the brain electrical activities recorded in real time through the electrical impulses emitted by the brain waves of the user. The achieved target is to identify and sort in real time the different brain states and adapt the interface and/or stimuli to the corresponding emotional state of the user. The setup of an experimental facility based on an innovative experimental methodology for “man in the loop" simulation was established. It allowed involving during pilot training in virtually simulated flights, both pilot and flight examiner, in order to compare the subjective evaluations of this latter to the objective measurements of the brain activity of the pilot. This was done recording all the relevant information versus a time-line. Different combinations of emotional intensities obtained, led to an evaluation of the current situational awareness of the user. These results have a great implication in the current training methodology of the pilots, and its use could be extended as a tool that can improve the evaluation of a pilot/crew performance in interacting with the aircraft when performing tasks and procedures, especially in critical situations. This research also resulted in the design of an interface that adapts the control of the machine to the situation awareness of the user. The new concept worked on, aimed at improving the efficiency between a user and the interface, and gaining capacity by reducing the user’s workload and hence improving the system overall safety. This innovative research combining emotions measured through electroencephalography resulted in a human-machine interface that would have three aeronautical related applications: • An evaluation tool during the pilot training; • An input for cockpit environment; • An adaptation tool of the cockpit automation.

Silk Fibroin: a biopolymer platform for innovative pharmaceutical formulation and biomedical devices.

The protein silk fibroin (SF) from the silkworm Bombyx mori is a FDA-approved biomaterial used over centuries as sutures wire. Importantly, several evidences highlighted the potential of silk biomaterials obtained by using so-called regenerated silk fibroin (RSF) in biomedicine, tissue engineering and drug delivery. Indeed, by a water-based protocol, it is possible to obtain protein water-solution, by extraction and purification of fibroin from silk fibres. Notably, RSF can be processed in a variety of biomaterials forms used in biomedical and technological fields, displaying remarkable properties such as biocompatibility, controllable biodegradability, optical transparency, mechanical robustness. Moreover, RSF biomaterials can be doped and/or chemical functionalized with drugs, optically active molecules, growth factors and/or chemicals In this view, activities of my PhD research program were focused to standardize the process of extraction and purification of protein to get the best physical and chemical characteristics. The analysis of the chemo-physical properties of the fibroin involved both the RSF water-solution and the protein processed in film. Chemo-physical properties have been studied through: vibrational (FT-IR and Raman-FT) and optical (absorption and emission UV-VIS) spectroscopy, nuclear magnetic resonance (1H and 13C NMR), thermal analysis and thermo-gravimetric scan (DSC and TGA). In the last year of my PhD, activities were focused to study and define innovative methods of functionalization of the silk fibroin solution and films. Indeed, research program was the application of different methods of manufacturing approaches of the films of fibroin without the use of harsh treatments and organic solvents. New approaches to doping and chemical functionalization of the silk fibroin were studied. Two different methods have been identified: 1) biodoping that consists in the doping of fibroin with optically active molecules through the addition of fluorescent molecules in the standard diet used for the breeding of silkworms; 2) chemical functionalization via silylation.

Analisi preliminare di combustioni innovative su un motore diesel di piccola cilindrata

Analisi delle emissioni di inquinanti per combustioni innovative Dual-Fuel e Premixed Charge Compression Ignition (PCCI) operate su un motore Diesel, nel laboratorio di propulsione e macchine della Scuola d'Ingegneria e Architettura con sede a Forlì. Tale studio è stato realizzato in quanto la riduzione delle emissioni e dei consumi sono caratteristiche di primo impatto per la competitività sul mercato di un motore e poiché le emissioni di inquinanti sono regolate da standard europei che ne esigono la continua riduzione. L'obiettivo della ricerca è quello di definire un pattern di combustioni, variando il valore e la sincronizzazione dei parametri delle attuazioni, che consenta la riduzione di inquinanti senza compromettere le prestazioni. Capire come ottenere minori emissioni di inquinanti significa poter far rientrare anche i motori diesel nelle future normative EURO 6 (già definite ed in vigore da Settembre 2014), e di seguire studi paralleli sulla riduzione dei consumi sui quali sono già stati riscontrati risultati positivi.

Innovative asymmetric organocatalytic processess: en route to the synthesis of biologically relevant compounds

This doctoral thesis deals with the development of novel organocatalytic strategies for asymmetric transformation. The intrinsic versatility of organocatalysis and the use of different activation modes have been exploited to achieve new catalytic enantioselective processes, towards the synthesis of biologically relevant scaffolds. The most investigated organocatalytic system have been those based on H-bond interaction (such as chiral thioureas or phosphoric acids) as well as the ones based on aminocatalysis. Despite conceptually distinct, the transformations detailed in this Thesis are linked together by simple and recurring modes of activation, induction and reactivity, promoted by the catalysts employed. The chemical diversity of the challenges encountered allows to get a precious overall view on organocatalysis, highlighting that enormous chemical diversity can be created by judicious choice of select catalyst.

Sviluppo di metodologie innovative di supporto decisionale alla progettazione basate su indicatori di prestazione

Il progetto di ricerca è finalizzato allo sviluppo di una metodologia innovativa di supporto decisionale nel processo di selezione tra alternative progettuali, basata su indicatori di prestazione. In particolare il lavoro si è focalizzato sulla definizione d’indicatori atti a supportare la decisione negli interventi di sbottigliamento di un impianto di processo. Sono stati sviluppati due indicatori, “bottleneck indicators”, che permettono di valutare la reale necessità dello sbottigliamento, individuando le cause che impediscono la produzione e lo sfruttamento delle apparecchiature. Questi sono stati validati attraverso l’applicazione all’analisi di un intervento su un impianto esistente e verificando che lo sfruttamento delle apparecchiature fosse correttamente individuato. Definita la necessità dell’intervento di sbottigliamento, è stato affrontato il problema della selezione tra alternative di processo possibili per realizzarlo. È stato applicato alla scelta un metodo basato su indicatori di sostenibilità che consente di confrontare le alternative considerando non solo il ritorno economico degli investimenti ma anche gli impatti su ambiente e sicurezza, e che è stato ulteriormente sviluppato in questa tesi. Sono stati definiti due indicatori, “area hazard indicators”, relativi alle emissioni fuggitive, per integrare questi aspetti nell’analisi della sostenibilità delle alternative. Per migliorare l’accuratezza nella quantificazione degli impatti è stato sviluppato un nuovo modello previsionale atto alla stima delle emissioni fuggitive di un impianto, basato unicamente sui dati disponibili in fase progettuale, che tiene conto delle tipologie di sorgenti emettitrici, dei loro meccanismi di perdita e della manutenzione. Validato mediante il confronto con dati sperimentali di un impianto produttivo, si è dimostrato che tale metodo è indispensabile per un corretto confronto delle alternative poiché i modelli esistenti sovrastimano eccessivamente le emissioni reali. Infine applicando gli indicatori ad un impianto esistente si è dimostrato che sono fondamentali per semplificare il processo decisionale, fornendo chiare e precise indicazioni impiegando un numero limitato di informazioni per ricavarle.

Development of an innovative pyrolysis plant for the production of secondary raw materials

This project was born with the aim of developing an environmentally and financially sustainable process to dispose of end-life tires. In this perspective was devised an innovative static bed batch pilot reactor where pyrolysis can be carried out on the whole tires in order to recover energy and materials and simultaneously save the energy costs of their shredding. The innovative plant is also able to guarantee a high safety of the process thanks to the presence of a hydraulic guard. The pilot plant was used to pyrolyze new and end-life tires at temperatures from 400 to 600°C with step of 50°C in presence of steam. The main objective of this research was to evaluate the influence of the maximum process temperature on yields and chemical-physics properties of pyrolysis products. In addition, in view of a scale-up of the plant in continuous mode, the influence of the nature of several different tires as well as the effects of the aging on the final products were studied. The same pilot plant was also used to carry out pyrolysis on polymeric matrix composites in order to obtain chemical feedstocks from the resin degradation together with the recovery of the reinforcement in the form of fibers. Carbon fibers reinforced composites ad fiberglass was treated in the 450-600°C range and the products was fully characterized. A second oxidative step was performed on the pyrolysis solid residue in order to obtain the fibers in a suitable condition for a subsequent re-impregnation in order to close the composite Life Cycle in a cradle-to-cradle approach. These investigations have demonstrated that steel wires, char, carbon and glass fibers recovered in the prototypal plant as solid residues can be a viable alternative to pristine materials, making use of them to obtain new products with a commercial added value.

Studio di celle solari innovative basate su "multiple electron-hole generation"

L’aumento dei consumi energetici e la sempre maggiore attenzione posta al tema ambientale fanno delle energie alternative una valida alternativa alle fonti , quali carbone e petrolio,che presentano una elevata generazione di gas serra . Tra le varie fonti alternative di energia un ruolo preponderante è stato assunto dal solare fotovoltaico, che dagli anni ’80 ad oggi ha conosciuto un rapido sviluppo sia in termini di ricerca che di utilizzo su larga scala. Negli ultimi anni tutti gli studi si stanno concentrando su un nuovo tipo di fotovoltaico, quello di terza generazione , il cui scopo è quello di ottenere dispositivi che possano garantire elevate efficienze in modo tale che la tecnologia fotovoltaica sia in grado di affermarsi definitivamente nel settore dell’energia. Il presente lavoro di tesi analizza il processo di conversione fotovoltaica ed il principio di funzionamento delle celle solari . I limiti termodinamici per l'efficienza di conversione di celle solari a singola giunzione sono stati discussi nella tesi. E' presentata nella tesi una rassegna delle principali strategie per il superamento dei limiti termodinamici per l'efficienza di una cella solare a singola giunzione . Sono stati analizzati : •il processo di rilassamento intrabanda dei nanocristalli ; •la generazione multipla di eccitoni (MEG) •il processo di Generazione di eccitoni multipli in nanocristalli di silicio colloidali (MEG in Si NCs). Tali risultati rivestono un particolare interesse per lo sviluppo di celle solari innovative , ad alta efficienza di conversione , utilizzando un materiale facilmente reperibile ed economico come appunto è il Silicio.