Dipartimento di Ingegneria dell'Ambiente - Tesi di Dottorato
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Questa collezione raccoglie le Tesi di Dottorato afferenti al Dipartimento di Ingegneria per l'Ambiente e il Territorio e Ingegneria Chimica dell'Università della Calabria.
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Item <> costruzione di possibili profili di sostenibilità applicati a scala di quartiere.(2013-11-29) Manfredi, Emilia; Pantano, Pietro; Rossi, FrancescoItem Innovative UV-LED polymerised bicontinuous microemulsion coating for membranes with special emphasis on MBRs(2017-07-11) Schmidt, Slefan-André; Pantano, Pietro; Curcio, Efrem; Gabriele, Bartolo; Figoli, AlbertoThe main objective of this work is the preparation of polymerisable bicontinuous microemulsion (PBM) coatings applied onto commercial membranes for improving the anti-fouling properties and performance, in terms of water flux and foulants rejection. Microstructured and nanostructured materials obtained by PBM have been widely investigated in the course of the last 30 years. The interest in microemulsion lies mainly in the possibility of dissolving larger amounts of oil and water by using polymerisable and non-polymerisable surfactants. By polymerising the bicontinuous microemulsion it is possible to produce transparent porous polymeric solids [Gan et al. (1995), Gan and Chew (1997)]. This thesis represents the follow-up of the work done by Galiano et al. (2015) and Deowan et al. (2016). Galiano et al. (2015) developed the PBM composition that based on a non-polymerisable surfactant (DTAB) and another polymerisable surfactant (AUTEAB). In their work the PBM was polymerised by redox initiators leading to a process that is very difficult to up-scale for a commercial application. Critical issues were, the polymerisation time (at least 20 minutes), and the reproducibility of the coating. Therefore, it is the aim of this work to develop another polymerisation technique that increases the polymerisation speed and allows the easy reproduction of membranes with defined properties. The polymerisation by photoinitiators excited by UV-light represents a promising possibility for this requirement as it has the potential of decreasing the polymerisation time down to a few seconds. Several photoinitiators were selected for their compatibility with the PBM, and studied for their conversion rate efficiency (section 5.1.5). As there is a wide range of potential UV-light sources available, several technologies are studied for their coating performance (section 5.1.3). Subsequent to that, experiments were done in order to define the ideal photoinitiator type and concentration while polymerising onto glass plates. The coating onto commercial membranes is studied deeply for e.g. different casting knife thickness or ambient temperature (section 5.2.2 As the polymerisation under inert conditions is expected to increase the polymerisation speed, experiments are done, both under inert and non-inert conditions. The final membrane, coated under the optimum conditions, is further characterised for their permeability under different conditions like transmembrane pressure (TMP), model foulant experiments and a fixed volume flow (section 5.2.3). Further characterisation is done by contact angle, SEM, AFM (section 5.2.5 to 5.2.7). The prepared PBM membranes are foreseen to be finally applied for model textile dye wastewater treatment by Membrane BioReactor (MBR) technology. According to the previous results of Deowan et al. (2016) higher permeate quality through increased COD, TOC, dyestuffs removal efficiency and stronger anti-fouling properties are expected. Consequently, lower operation/maintenance costs due to reduced necessary aeration for scouring purposes and reduced membrane cleaning cycles as well as less membrane replacement are of special interest for commercial applications. In the previous work of Deowan et al. (2016) a lab scaled MBR with a single membrane housing was used. As of the biocenosis of the bacteria inside the reactor tank, a comparison of the membrane performance of the PBM and commercial membrane is difficult to achieve. Therefore an existing MBR system was redesigned to allow the simultaneous run of a commercial and a PBM coated membrane (section 4.1). As the revamp requires also additional sensors, the data acquisition needs to be adapted as well. To assure the proper function of the MBR the system was running for long term with two commercial membranes using a model textile wastewater (see 5.3.2). Finally the PBM coated membrane was compared with a commercial one for their performance in the MBR. Initial experiments for the water permeability are done as preparation for future work (see 5.3.3).Item Dynamic operation and control of cell culture environments in bioreactors for bioartificial liver application(2017-07-11) Naghib, Seyed Danial; Pantano, Pietro; Di Renzo, Alberto; Curcio, Efrem; Di Maio, Francesco Paolo; De Bartolo, LoredanaOn the global scale, liver diseases are severe public health problems, with the incidences of end-stage liver disease (ESLD) rising annually. Isolated hepatocytes represent a good model of liver metabolism because they are able to perform the full range of functions. In recent years, biochemical and biotechnological engineering have been applied to the culture of human and animal hepatocyte cells, which requires the design, operation, and control of complex appropriate bioreactors. In this work, the predictable, stable and durable operation of two types of bioartificial reactors for cell cultures is investigated. The thesis is divided into the following two parts. Part I: Fluidized bed bioreactor Fluidized-bed-based biomedical devices acting as bioartificial liver, in which cells are trapped and encapsulated into appropriated fluidized beads, have proved effective solutions to many respects. However, the bioreactor performance is significantly affected by the hydrodynamics and mass transfer, not well characterized yet for most aspects. In the present work, the intrinsic and fluidization properties of alginate beads as encapsulation medium for hepatic cells are carefully analyzed experimentally using two rigs at different scales. Appropriate alginate beads were prepared and characterized in terms of size distribution and density. Expansion properties were evaluated for free alginate beads (i.e. without hepatic cells) using saline (Ringer) solutions as fluidization medium. Bed expansion tests over a wide range of voidage values have been conducted in a 1-cm diameter column, used for perfusion during in vitro experiments, as well as in a 10-cm diameter column close to human size bioreactor, in the latter case at two temperatures: ambient (20°C) and human body (37°C) conditions. Full fluid-dynamic characterization of the alginate beads is conducted, including expansion data, terminal velocity measurements, and velocity-voidage plots and their elaboration in terms of Richardson-Zaki parameters. Part II: Hollow fiber membrane bioreactor Due to their structure affine to the physiological environment in vivo, hollow fibre membrane bioreactors in crossed configuration can provide favourable conditions for the cell behaviour and metabolism. Specific devices have been proposed in recent years with very promising potential for applications. To be able to develop bioartificial systems that operate effectively and for the long term, in addition to handling the biological complexities, fluid dynamics and transport phenomena require an advance model, careful control, and appropriate automation strategies. Tight control of the culturing environment and strategies for dealing with some inherently unsteady changes of conditions in a membrane bioreactor is investigated by developing and implementing a new hydrodynamic dual control system for an existing bioreactor prototype. The experimental implementation of the sensors-controllers-actuators system is complemented by the development of a transient mathematical model of the instrumented bioreactor, in which the membrane unit is treated as a three-compartment model. A four-input/seven-state transient model of the bioreactor is obtained, able to describe the time evolution of the flowrates, the extra-capillary space liquid level and the oxygen concentration across the system. The selection of appropriate sensors and the manipulated control variables is discussed. Bioreactor dynamic simulation and control is carried out within the Matlab/Simulink environment and Matlab is also used as a platform for the experimental data digital acquisition and control logic implementation (e.g. controller tuning), allowing both for flexibility with testing of different control schemes and for direct comparison of simulated and experimental values. Different experiments with selected input changes were carried out under idealized conditions and using water as perfusing medium. The applied stimuli served to mimick causes of previously observed bioreactor malfunctions (e.g. high sensitivity to liquid level variations during prolonged cell culturing experiments) and check the control system efficacy and efficiency. Finally, the developed control system is utilized during a prolonged experiment of multi-cell culture within the membrane bioreactor, demonstrating the reliable, continuous and successful cultivation for nearly one month time. The set of results collected during the present work allows to achieve new insight into the operation and reliability of bioreactors for application as bioartificial devices, by improving the capacity to predict their behaviour and better design their structure as well as by enhancing the control over the cell culture environment conditionsItem Development of Tailored Hydrogel Composite Membranes for Application in Membrane Contactors(2017-07-11) Majidi Salehi, Shabnam; Pantano, Pietro; Curcio, Efrem; Di Profio, Gianluca; Fontananova, EnricaThis work was performed during the period from November 2013 to May 2015 in the Institute on Membrane Technology (ITM-CNR) at the University of Calabria (UNICAL), under supervision of Prof. Efrem Curcio, Dr. Gianluca Di Profio and Dr. Enrica Fontananova, from May 2015 to December 2015 at Universidade Nova de Lisboa (UNL), under supervision of Prof. Joao Crespo and from March 2016 to September 2016 at the University of Chemistry and Technology (ICT) Prague, under supervision of Dr. Eng. Vlastmil Fila. The main objective of this study was to design and develop tailored hydrogel composite membranes for application in membrane contactors, in particular, membrane distillation and membrane crystallization. Among various methods for membrane surface functionalization, surface photo-initiated graft polymerization technique (at UNICAL) and surface coating by incorporating nanoparticles (at UNL) were investigated to fabricate tailored hydrogel composite membranes In the first year at the University of Calabria, various hydrogel composite membranes were prepared by using photo-initiated polymerization method. The possibility of fine tuning the porosity and the chemical nature of hydrogels, were implemented with the preparation of composites containing diverse hydrogel components (monomer and cross-linker) and ratio among them. The selection of hydrogel components was based on the possibility to obtain homogeneous and stable composites by using specific polymeric porous membranes as supports. The resulting composite membranes were characterized by electron scanning microscopy, surface chemistry analysis, swelling degree, ion exchange capacity and water contact angle measurements Furthermore, virgin and hydrogel composite membranes were used in membrane distillation and crystallization experiments and the performance improvement was evaluated. As a result, higher water-transfer flux and enhanced ion rejection than traditional MD membranes was observed in MD treatment of saline solutions. When such HCMs used in membrane assisted crystallization of carbonate calcium (biomineralization), a wide range of crystal morphologies, most of them displaying a polycrystalline or mesocrystalline structure, was obtained in a great variety of experimental conditions. We demonstrated that this composite provides the opportunity to fine control the delivery of additives to the gel network through the porous structure of both support membrane and hydrogel layer, thus affecting crystallization kinetics, and crystal morphologies In the second year of the study at Universidade Nova de Lisboa, hydrogel composite membranes with tailored surface roughness and patterning were designed to examine the influence of the topography of such composite membranes on the growth of protein crystals. Iron oxide nanoparticles (NPs) were used as topographical designers providing a good control of membrane surface roughness and patterning. Surface morphology and topography of the prepared membranes were characterized using electron scanning microscopy, profilometry analysis and contact angle measurements. Finally, their performance was evaluated in the crystallization of Lysozyme used as a model protein and the effect of surface chemistry and topography on the heterogeneous nucleation of lysozyme crystals was investigated. We demonstrated that roughness influences crystallization, but we also show that excessive roughness may be deleterious, since it increases the number of crystals formed at the expenses of crystal size. Therefore, there is an optimum value of roughness for the formation of a low number of well-faced crystals with a larger size In the third year at the University of Chemistry and Technology Prague, the modeling of membrane crystallization was studied. The main goal of this work was to develop general model of membrane crystallization process. The development of this model involved the fundamental theories and models in membrane process and crystallization engineering, especially the models described the mass and heat transfers in membrane module and the crystal size distribution (CSD) determined by both nucleation and crystal growth processes based on the concept of the population balance equation. The experimental results of this study, allows to achieve new insight to fabricate and develop the novel hydrogel composite membranes with proper properties and novel functionality for application in membrane distillation and membrane crystallization processesItem Mass and momentum transfer in membrane-based bioartificial liver systems(2017-07-11) Khakpour, Shervin; Pantano, Pietro; De Bartolo, Loredana; Curcio, EfremLiver failure, caused by acute or chronic end-stage liver disease (ESLD) imposes a significant disease burden worldwide. Chronic liver disease and cirrhosis is ranked as 12th cause of death in the United States and 4th in middle-aged adults. Researchers in Mayo Clinic report liver-related mortality as 8th by using a more comprehensive definition accounting for other aspects of liver disease as well. Currently, liver transplantation remains the conventional treatment for ESLD as the only medically proven method to promote patient’s health. To avoid the problem of inadequate donor organs and yet provide a comprehensive range of liver functions, cell-based therapies have been actively under investigation to potentially provide a substitute for transplantation, or a temporary support for liver failure patients. Studies on the latter aim has led to development of extracorporeal bioartificial liver (BAL) devices. Hepatic cell cultures are exploited for different applications in liver disease studies, drug toxicity testing, and bioartificial liver (BAL) devices. However, development of such systems is often hindered by the peculiar characteristics and intricate requirements of primary hepatocytes, challenging their prolonged functionality and viability in vitro. Despite the development of various 3D cell culture systems using perfused bioreactors, mass transfer properties still remain a critical and controversial topic, especially oxygen supply as the limiting and modulating factor The aim of this work is to enhance and optimize a prototype hollow fiber membrane bioreactor (HFMBR) providing efficient mass transfer for nutrient provision and catabolite removal, promoting prolonged viability and functionality of hepatocytes. In this bioreactor, two bundles of hollow fibers are employed in a crossed configuration: one bundle for supplying the oxygenated medium, and the other for removing the medium from the extra-capillary space. Optimization of the operational culture conditions to enforce an in vivo-like microenvironment is an intrinsic part of the process that requires a clear understanding of the in vitro cellular microenvironment. Oxygen transport in a convection-enhanced, crossed-configuration HFMBR hosting hepatocyte spheroids was investigated through mass transfer modelling using COMSOL Multiphysics®, a specialized, commercial finite-element software. The permeability of hollow fibers (hydraulic, albumin solution) was evaluated experimentally, showing significant, irreversible decrease in the permeance of the membranes due to protein absorption during culture period. Bioreactor’s hydrodynamics was investigated through residence time distribution analysis, by which a portion of the bioreactor was diagnosed as stagnant region. Finally, oxygen diffusion through the medium and the effect of different conditionings on the oxygen sensor’s readings in multi-well plates were studied. Mass transfer in static culture systems – both as a monolayer and as spheroids – was evaluated using a diffusion-reaction model numerically solved for oxygen (steady-state study) and urea (time-dependent study). In addition to the size and number of spheroids, sufficiency of oxygen supply to cells also depended on their distribution (the distance between them) and the amount of culture medium in each well. A convection-diffusion-reaction time distribution analysis, by which a portion of the bioreactor was diagnosed as stagnant region. Finally, oxygen diffusion through the medium and the effect of different conditionings on the oxygen sensor’s readings in multi-well plates were studied. Mass transfer in static culture systems – both as a monolayer and as spheroids – was evaluated using a diffusion-reaction model numerically solved for oxygen (steady-state study) and urea (time-dependent study). In addition to the size and number of spheroids, sufficiency of oxygen supply to cells also depended on their distribution (the distance between them) and the amount of culture medium in each well. A convection-diffusion-reaction time distribution analysis, by which a portion of the bioreactor was diagnosed as stagnant region. Finally, oxygen diffusion through the medium and the effect of different conditionings on the oxygen sensor’s readings in multi-well plates were studied. Mass transfer in static culture systems – both as a monolayer and as spheroids – was evaluated using a diffusion-reaction model numerically solved for oxygen (steady-state study) and urea (time-dependent study). In addition to the size and number of spheroids, sufficiency of oxygen supply to cells also depended on their distribution (the distance between them) and the amount of culture medium in each well. A convection-diffusion-reaction time distribution analysis, by which a portion of the bioreactor was diagnosed as stagnant region. Finally, oxygen diffusion through the medium and the effect of different conditionings on the oxygen sensor’s readings in multi-well plates were studied. Mass transfer in static culture systems – both as a monolayer and as spheroids – was evaluated using a diffusion-reaction model numerically solved for oxygen (steady-state study) and urea (time-dependent study). In addition to the size and number of spheroids, sufficiency of oxygen supply to cells also depended on their distribution (the distance between them) and the amount of culture medium in each well. A convection-diffusion-reaction model was developed to describe momentum and mass transfer in the bioreactor, in which the influential parameters were parametrized through implementation of applicable correlations. The model was numerically solved for two different types of geometries: (i) single-spheroid model using a periodic/symmetric unit cell within the bioreactor to locally represent the system decreasing the computational complexity of the model, (ii) miniaturized bioreactor model. The single-spheroid model was used to carry out a systematic parametric study to evaluate the effect of different parameters – oxygen tension (Co,sat), perfusion rate (QBR), hollow fiber spacing (δHF), spheroid diameter (Dsph), Michaelis-Menten kinetics for oxygen uptake (Vmax, Km) and porosities of the spheroid (εcc) and the membrane (εm) – on dissolved oxygen concentration (DOC) profile. Dimensionless numbers were defined for in-depth analysis of oxygen transfer and how each parameter can affect that. Among the operational conditions, Co,sat was found much more influential than QBR. Due to the mild advection added, the extra-spheroid resistances to diffusive mass transfer, i.e. the membrane (governed by εm) remains an important factor. However, εcc was found as a key intrinsic property strongly affecting intra-spheroid DOC profile. Maintaining physiological DOC range in large spheroids (Dsph=400μm) with different porosities was investigated in the single-spheroid model. Regulation of DOC profile was more manageable in spheroids with higher εcc, which lead to feasibility of achieving physiological oxygen concentrations. Low-porosity spheroids demonstrated a sharper concentration gradient, challenging sufficient oxygen supply to cells. Temporal shrinkage of spheroids due to rearrangement of cells changes the microstructure of the spheroid, the effect of which was numerically studied and proved to adversely affect the transport properties and consequently the DOC profile inside the spheroid. In the end, values from an experimental study were incorporated into the model to analyze the cellular microenvironment during the experiment, and the predictive capacity of the model regarding the outcome. Miniaturized bioreactor model was developed to reduce the computational cost while providing a more realistic model for the bioreactor. Another major advantage of this approach is capacitating investigation of the fluid dynamics inside the bioreactor. Notable DOC drop along the lumina of the supplying bundle was observed, consistent with the DOC gradient in the extra-capillary space along the supplying bundle. Having retentate flow in the hollow fibers significantly reduced these gradients and improved oxygen supply to the cells. Oxygen transfer was not noticeably affected by different flow patterns realized through using both bundles supplying or both removing the medium. However, minimization of the stagnant region had in fact a negative influence on oxygen supply. The miniaturized bioreactor model was also modified based on the experimental results for comparison with the single-spheroid model and the actual bioreactor, showing better compatibility with the real case.Item Performance of hollow fiber membrane bioreactor as a bioartificial liver(2017-07-11) Magdy Ahmed, Haysam Mohamed; Pantano, Pietro; De Bartolo, Loredana; Curcio, EfremC'è una crescente necessità di sviluppare un dispositivo bioartificiale di tipo epatico da utilizzare sia in applicazioni in vitro, per la sperimentazione della tossicità di molecole da parte delle aziende farmaceutiche, e sia in applicazioni cliniche per supportare pazienti con insufficienza epatica in attesa di trapianto di organo. A tale scopo è stato realizzato un bioreattore a membrana a fibre cave incrociate adoperante cellule epatiche umane in grado di favorire il mantenimento a lungo termine di epatociti. Il bioreattore è costituito da due fasci di membrane a fibre cave (HFM), uno deputato all’alimentazione e l’altro alla rimozione di cataboliti e prodotti specifici cellulari. I due fasci di fibre sono assemblati in una configurazione incrociata ed alternata in modo da stabilire una distanza l’una dall’altra di 250 μm. Questa configurazione del bioreattore delinea tre compartimenti separati: due compartimenti all’interno del lumen delle fibre cave dove il mezzo di coltura fluisce e un compartimento extraluminale dove le cellule sono coltivate. I compartimenti intraluminali ed extraluminale comunicano tra di loro attraverso i pori della parete di membrana. Il mezzo che fluisce nel lumen delle fibre di alimentazione permea nel compartimento cellulare, dove i cataboliti ed i metaboliti prodotti dalle cellule vengono rimossi dalle fibre cave deputate all’allontanamento dei molecole di sintesi e di scarto cellulari. In questo dispositivo le membrane a fibre cave consentono la compartimentalizzazione delle cellule in un microambiente controllato a livello molecolare ed il trasporto selettivo di molecole verso e dal compartimento cellulare proteggendo le cellule da eventuali sforzi di taglio. Inoltre, le membrane, grazie alla loro geometria intrinseca, offrono un'ampia superficie per l'adesione e la crescita delle cellule in un volume ridotto. Epatociti umani rappresentano una fonte cellulare ottimale da utilizzare nelle terapie che sono basate sull’uso di cellule, in quanto riflettono più da vicino le condizioni in vivo. In vivo gli epatociti sono altamente proliferativi all'interno del loro microambiente. Tuttavia, quando sono isolati dal loro microambiente e coltivati in vitro, perdono rapidamente le loro funzioni specifiche. Pertanto, è di importanza fondamentale la realizzazione di modelli in vitro in grado di mantenere gli epatociti vitali e funzionali per lungo tempo. Un aspetto critico è la la scarsa disponibilità di epatociti umani per cui occorre prendere in considerazione fonti cellulari alternative. Gli studi effettuati in questi ultimi anni indicano come una delle migliori fonti cellulari alternativa agli epatociti le cellule staminali, poiché queste cellule sono ampiamente disponibili possiedono in vitro un’elevata capacità proliferativa e possono essere differenziate in epatociti. A differenza delle cellule provenienti da animali e delle linee cellulari, le cellule staminali non costituiscono un rischio di trasmissione virale zoonotica o tumorigenicità. In questo lavoro, il bioreattore a membrana è stato ottimizzato al fine di creare condizioni di coltura per aggregati cellulari come sferoidi e per sistemi organotipici tridimensionali (co-coltura di epatociti e cellule non parenchimali) che garantiscano il mantenimento a lungo termine della funzionalità dei costrutti epatici umani. A tal proposito, le funzioni specifiche epatiche come l'urea, la sintesi dell'albumina e la biotrasformazione di farmaci sono state valutate nel bioreattore. I cambiamenti morfologici cellulari sono stati analizzati utilizzando il microscopio elettronico a scansione ed il microscopio confocale a scansione laser. Inoltre, il consumo di ossigeno delle cellule poste in coltura nel bioreattore è stato continuamente monitorato nel tempo al fine di assicurare un adeguato approvvigionamento di ossigeno. Gli sferoidi epatici umani, posti in coltura nello spazio extracapillare del bioreattore sono andati incontro ad un processo di fusione che ha portato alla formazione di strutture di maggiore dimensione simili a microtessuti. La fusione degli sferoidi è stata osservata sia tra le fibre che intorno alle fibre simulando il processo che avviene in vivo. Questo modello di coltura, grazie alle sue caratteristiche tridimensionali e all'aumentata interazione cellulare, così come avviene in vivo, ha favorito il mantenimento a lungo termine della vitalità e delle diverse funzioni specifiche epatiche come la sintesi di albumina ed urea ed il metabolismo xenobiotico. Allo stesso modo, nel sistema organotipico, le cellule si riorganizzano formando strutture tissutali simili a quelle del tessuto epatico in vivo. Questo è stato reso possibile grazie al piastramento sequenziale sulle membrane di cellule non parenchimali e parenchimali che hanno formato strutture stratificate tridimensionali simili a quelli in vivo. Il bioreattore che è stato ottimizzato in questo lavoro di tesi fornisce un microambiente di coltura ben controllato da un punto di vista molecolare attraverso l'alimentazione continua di sostanze nutritive, di cui una delle più importanti è l'ossigeno, e la rimozione di cataboliti. Ciò è stato confermato dai risultati relativi alla misura della concentrazione di ossigeno nel mezzo di coltura sia nella corrente in ingresso che in uscita dal bioreattore. In entrambi i modelli di coltura, l'approvvigionamento di ossigeno nel bioreattore è risultato essere sufficiente e significativamente maggiore a quello osservato in condizioni di coltura statica. Inoltre, una nuova fonte di cellule staminali, ovvero le cellule staminali mesenchimali derivate dal fegato, è stata utilizzata: le cellule sono state differenziate con successo in epatociti dopo 24 giorni di coltura, sia nel sistema statico che nel bioreattore. Tuttavia, il bioreattore ha mostrato una migliore capacità di mantenere la vitalità delle cellule e di differenziare le cellule staminali mesenchimalinel fenotipo epatico, come dimostrato dall'aumento dell'espressione genica di marcatori epatici specifici (ad es. albumina ed il fattore nucleare epatico alfa-4) e dalle velocità di sintesi di urea e albumina. Il prototipo di bioreattore realizzato su scala di laboratorio ha mantenuto con successo e funzionalmente attivi gli epatociti umani coltivati come sferoidi e in co-coltura con cellule non parenchimali per quasi un mese. Un aspetto importante è stato il differenziamento epatico delle cellule staminali mesenchimali, che rappresentano una potenziale fonte di cellule alternativa agli epatociti umani primari. Tutti questi risultati sono stati ottenuti utilizzando solo cellule umane, che convalidano le prestazioni del dispositivo che è stato sviluppato come sistema epatico bioartificiale da utilizzare in vitro. Questo bioreattore su scala di laboratorio ha un elevato potenziale applicativo cha va dagli studi in vitro delle malattie epatiche agli studi di tossicità a lungo termine. Inoltre, può essere realizzato su scala clinica ed applicato come fegato biartificiale per sostituire le funzioni epatiche di pazienti affetti da insufficienza epatica in attesa di trapianto.Item Charged-particle distributions and material measurements in ps = 13 TeV pp collisions with the ATLAS Inner Detector(2017-07-14) Cairo, Valentina Maria Martina; Pantano, Pietro; Dell'Acqua, Andrea; Schioppa, MarcoThe Run 2 of the Large Hadron Collider, which began in Spring 2015, offers new challenges to the Experiments with its unprecedented energy scale and high luminosity regime. To cope with the new experimental conditions, the ATLAS Experiment was upgraded during the first long shutdown of the collider, in the period 2013-2014. The most relevant change which occurred in the ATLAS Inner Detector was the installation of a fourth pixel layer, the Insertable B-Layer, at a radius of 33 mm together with a new thinner beam pipe. The Pixel Services, located between the Pixel and SCT detectors, were also modified. Owing to the radically modified ID layout, many aspects of the track reconstruction programs had to be re-optimized. In this thesis, the improvements to the tracking algorithms and the studies of the material distribution in the Inner Detector are described in detail, together with the improvements introduced in the geometry model description in simulation as well as the re-evaluation and the reduction of the systematic uncertainty on the estimate of the track reconstruction efficiency. The results of these studies were applied to the measurement of Charged-Particle Multiplicity in proton–proton collisions at a centre-of-mass energy of 13 TeV. The chargedparticle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on the charged-particle multiplicity are presented for various fiducial phase spaces. The measurements are corrected for detector effects, presented as particle-level distributions and are compared to the predictions of different Monte Carlo event generators. New sets of recommended performance figures along with the related systematic uncertainties were also derived for several aspects of the ATLAS tracking, such as track reconstruction efficiency, fake rate and impact parameter resolution. These recommendations provide information on appropriate working points, i.e. track selection criteria with wellunderstood performance. They apply to physics analyses using Inner Detector tracks in Run 2 data and are important inputs for other objects based on tracks, such as jets. A simulation-based method which uses the tracking recommendations to calibrate light-jets mis-tagged as b-jets it is also presented in the context of the measurement of the crosssection of the W-boson produced in association with b-jets at 13 TeV, together with an overview of the inclusiveW-boson cross-section analysis.Item Geo-referencing devices based on retroreflectors for Galileo and earth observation(2017-07-11) Contessa, Stefania; Pantano, Pietro; Dell'Agnello, SimoneItem Improving General Relativity tests with innovative Lunar and Martian retrore ector payloads(2017-07-11) Ciocci, Emanuele; Pantano, Pietro; Dell'Agnello, SimoneItem Valutazione della scuscettibilità e degli scenari di pericolosità e di rischio da frana in aree di interesse socio-economico (Calabria Settentrionale)(2016-02-02) Rago, Valeria; Pantano, Pietro; Gagliardo, Pietro; Muto, FrancescoLandslides are natural geologic processes that play a key role in landscape evolution, but represent also one of the most widespread natural hazard in Italian territory. In particular, many areas of the Calabria region (southern Italy) have been affected historically by mass movements, due to the combination of its peculiar geological, morphological, seismic and climatic features and frequently to regionally unsustainable land management. Landslides are responsible for direct and indirect damages, may cause loss of life and property, damages to natural resources and hamper infrastructure projects, by generating strong social and economic impacts. This resulting in millions of Euro per year in damages and restoration as well. Therefore, spatial identification of potentially unstable slopes and landslide risk evaluation are very important in order to get mitigation measures and for land planning. The aim of this study is landslide susceptibility and risk assessment in areas of socio-economic interest in Northern Calabria. Study areas were a section of the A3 highway and a part of Amendolara town. The identification and selection of study areas took into account topography, geology and urban development conditions for which the landsliding is potentially a problem. Landslide risk assessment in the section of A3 highway was performed in a qualitative way by overlapping the highway on the landslide susceptibility map; this had lead to the zonation of spatial risk which allowed an evaluation of the involvement of the highway in the different susceptibility areas. In the Amendolara territory risk assessment was carried out in a quantitative way according to the formula: Risk = Hazard × Vulnerability × Economic value of elements at risk (buildings and roads). Hazard was computed in a probabilistic way by means the product between spatial probability (probability that any given region will be affected by landslides), temporal probability (probability of occurrence of landslide events during time t) and probability of landslide size (probability that a landslide will have a certain size). Physical vulnerability was evaluated considering elements at risk features and landslide size. Finally, landslide risk was computed on the basis of economic value of elements at risk, pointing to the probability of money that can be lost at the occurrence of a landslide in a given area, in a certain interval of time and with a certain area. This study provides two case example for the qualitative and quantitative risk assessment which can be useful to planners and decision makers to identify areas where more damages are expected and that should receive priority in the use of limited resources directed to preventive plans to reduce the impact of the landslides.