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Model-based optimization of radial flow packed-bed bioreactors for tissue engineering
(2016-01-13) Donato, Danilo; Canonaco, Canonaco; Catapano, Gerardo; Segers, Patrick
Tissue loss or organ failure represents one of the major problems in human health care, and is responsible of impressive social and economic costs worldwide. Current approaches to restore tissues or organs functions consist in tissue replacement with allogeneic or xenogeneic grafts, taken from donors or animals, respectively, or autologous grafts, taken from the patient himself. The use of allogenic and xenogenic grafts is severely limited by the donor shortage and by the difficult integration of the donor tissue within the patient body. Tissue replacement with autografts, although avoiding the risk of immune rejection by the patient, is limited by donor-site morbidity, so that it may be adopted only for small-scale tissue losses. In recent years, tissue engineering has been proposed as a promising alternative to tissue replacement with artificial grafts. According to this approach, biological engineered substitutes for tissue replacement are realized by seeding isolated autologous cells onto three-dimensional (3D) porous supports, termed scaffolds, and by guiding cell proliferation and differentiation in bioreactors, that provide the physiological pericellular environment for tissue development. The major issue for the realization of clinical-scale bioengineered substitutes for tissue replacement is the difficult supply of physiological amounts of dissolved oxygen and nutrients to, as well as metabolic wastes removal from, the cells located in the innermost regions of the 3D constructs (i.e. cell-seeded scaffolds). In particular, it is generally acknowledged that the severe consumption of dissolved oxygen by the cells represents the major limitation for cell survival in the development of bioengineered tissues. Static cultures in which dissolved oxygen and nutrients are supplied to the cells by pure diffusive transport have been shown to enable cell survival only to small-scale constructs. In order to overcome transport limitations of static cultures, dynamic bioreactors have been proposed in which a certain degree of convection is superimposed to pure diffusion to enable solutes transport towards, or away from, the innermost region of large-scale constructs. However, although some improvements over static cultures have been evidenced, dynamic bioreactors proposed so far, such as spinner flasks, rotating wall vessels and direct axial perfusion bioreactors, are still sub-optimal for the realization of clinical-scale bioengineered tissues. Recently, radial perfusion of hollow cylindrical 3D constructs in radial flow packed-bed bioreactors (rPBBs) has been proposed to overcome the limitations of both static and direct axial perfusion bioreactors, in particular for the development of bioengineered liver and bone tissues. In fact, since culture medium is perfused radially to the cells, shorter path lengths and larger cross-sectional areas for solutes transport are featured than those in axial flow bioreactors, that enable cell culture at small pressure drops and superficial velocities, and smoother solutes concentration gradients in the direction of the medium perfusion. Despite these promising features, design of rPBBs is more difficult than that of axial flow packed bed bioreactors. In fact, rPBBs require two void chambers (i.e. the inner hollow cavity and the peripheral annular space) to distribute and collect culture medium flowing across the construct thickness, the fluid dynamics of which may significantly influence radial flux distribution of culture medium along the construct length. Furthermore, the annular construct geometry and the direction of medium perfusion may strongly affect the transport of solutes towards, or from, the cells. The extent of the perfusion flow rates have also to be chosen in order to ensure adequate mass delivery to cells while preventing cell damage and washout. Mathematical models of transport in rPBBs may help optimize bioreactor design for a given application to enable dissolved oxygen and nutrients delivery towards, and metabolic wastes removal from, 3D clinical-scale constructs. However, a systematic analysis of the influence of all the geometrical, transport and operational dimensionless groups on bioreactor behavior aimed to design rPBBs so that solutes transport towards, or from, the cells is maximized and controlled has not been reported yet. This limits the exploitation of the peculiar features of the rPBBs in the development of bioengineered substitutes for tissue replacement. In this thesis, a model-based reference framework is proposed to optimize rPBB design to ensure adequate environmental conditions to cells for the realization of clinical-scale 3D bioengineered substitutes for tissue replacement. In particular, the attention is paid on transport of dissolved oxygen, since its limiting role for the realization of large-scale 3D biological constructs is generally acknowledged. In order to reach the proposed objective, the workflow was divided in three different steps, as follows: 1. A reference framework was first developed based on a one-dimensional stationary transport model, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics, to optimize annular construct geometry and direction and extent of the radial superficial velocity of the culture medium across the cell mass for the culture of largescale 3D porous constructs, assuming that radial flux distribution of the culture medium was uniform along the construct length. Dimensional analysis was used to find the dimensionless groups determining bioreactor behavior, under typical conditions for tissue engineering. In particular, according to this model, bioreactor behavior was shown to depend on the perfusion flow direction parameter, g; the dimensionless construct Darcy permeability, kL/R3; the inner hollow cavity radius-to-construct thickness ratio, R/dC; the maximal radial Peclet number, Perad,max; the Thiele modulus, fC; the saturation parameter, b. The effectiveness of oxygen supply to the cells was expressed in terms of the non-hypoxic fractional construct volume. Model predictions suggest that outward perfusion (i.e. form the construct inner surface towards the outer peripheral surface) of 3D annular porous constructs having small curvature (i.e., high inner hollow cavity radius-to-annular thickness ratio) at high perfusion flow rates, (i.e high maximal radial Peclet numbers) may enhance dissolved oxygen supply to the cells as compared to cell culture in static and axial flow bioreactors. 2. A design criterion to optimize rPBB design in order to achieve uniform radial flux distribution of the culture medium along the construct length was obtained, based on a two-dimensional stationary transport model of momentum in all the rPBB compartments (i.e. inner hollow cavity, porous construct, peripheral annulus), assuming that medium is perfused outwards according to the results obtained with the 1D model. In particular, momentum transport in the void spaces of the rPBB was described according to the Navier-Stokes equation, whereas Darcy-Brinkman equation was used to describe momentum transport in the porous construct. Dimensional analysis showed that the uniformity of radial flux distribution of the culture medium along the construct length depends on: a reduced Reynolds number, Rein; the construct aspect ratio, L/R; the inner hollow cavity radius-toconstruct thickness ratio, R/dC; the inner hollow cavity radius-to-peripheral annulus thickness ratio, R/dE; the construct-to-hollow cavity permeability ratio, k/R2. The influence of R/dC and R/dE was lumped in one dimensionless group (i.e. the hollow cavity-to-peripheral annulus cross-sectional area ratio, x), as suggested by literature results. The design criterion, termed CORFU (Criterion Of Radial Flux Uniformity), was shown to depend on all the dimensionless groups found by dimensional analysis. In particular, according to the CORFU criterion, uniform radial flux distribution of the culture medium along the construct length may be achieved by adjusting the values of the dimensionless groups determining rPBB behavior in order to ensure that the ratio between the total axial pressure drop in the void spaces is maintained within ±10% of the radial pressure drop across the construct. 3. The momentum transport model was integrated with a mass transport model to assess the actual effect of the radial flux distribution of the culture medium along the construct length on dissolved oxygen transport and to design rPBBs for a given therapeutic objective. Transport of dissolved oxygen in the construct was described in terms of the convection-diffusion-reaction equation, and dissolved oxygen consumption was described according to the Michaelis-Menten kinetics. Oxygen mass transfer coefficients accounting for the external mass transport at cell/medium interface were estimated for a bed of Raschig rings transport-equivalent to porous scaffolds adopted for tissue engineering. Dimensional analysis showed that, in addition to the dimensionless groups obtained for the momentum transport model previously listed, bioreactor behavior, which was expressed in terms of the Non-Hypoxic Fractional Construct Volume, depends on the following dimensionless groups: the maximal radial Peclet number, Perad,max; the construct-to-hollow cavity diffusivity ratio, DC/DH (and, analogously, the construct-to-peripheral annulus diffusivity ratio, DC/DE); the Sherwood number, Sh; the saturation parameter, b; the Thiele modulus, fC; the squared surface Thiele modulus-to-Sherwood number ratio, fs 2/Shp. The effect of the dimensionless number on bioreactor behavior was investigated under working conditions typical of tissue engineering. Model predictions suggested how to optimize bioreactor design in order to ensure controlled oxygen supply to cells for different tissue engineering applications. Medium radial flux distribution was shown to significantly influence oxygen spatial distribution inside the construct under conditions in which oxygen depletion is not properly compensated by oxygen supply to cells. The effect of medium radial flux distribution on oxygen supply becomes less important if oxygen consumption is compensated by oxygen supply. Model predictions also suggest that higher Rein influences oxygen spatial distribution from the top towards the bottom of the bioreactor for non-uniform medium radial flux distribution, giving higher uniformity of oxygen distribution along bioreactor length. The radial perfusion rates have to be optimized not only to control radial flux distribution, but also to enable adequate supply of dissolved oxygen to the cells while preventing cell wash out, at any given stage of tissue development. In particular, model predictions suggest that at the beginning of the culture medium flow rates may be kept low to avoid cell damage or wash out, whereas, as cells proliferate and differentiate, the medium flow rates should be gradually increased to balance out the increasing metabolic requirements of cells. In particular, higher perfusion flow rates enable more adequate oxygen supply to cells for a given value of fC. Finally, choosing perfusion rates that cause minimal Damköhler number, Darad,min = fC 2/Perad,max, to be small were shown to ensure adequate pericellular oxygenation (i.e. NHy-FCV around 1) for tissue development
Model-based optimization of radial flow packed-bed bioreactors for tissue engineering
(2015) Donato, Danilo; Canonaco, Marcello; Catapano, Gerardo; Segers, Patrick
Tissue loss or organ failure represents one of the major problems in human health care, and is responsible of impressive social and economic costs worldwide. Current approaches to restore tissues or organs functions consist in tissue replacement with allogeneic or xenogeneic grafts, taken from donors or animals, respectively, or autologous grafts, taken from the patient himself. The use of allogenic and xenogenic grafts is severely limited by the donor shortage and by the difficult integration of the donor tissue within the patient body. Tissue replacement with autografts, although avoiding the risk of immune rejection by the patient, is limited by donor-site morbidity, so that it may be adopted only for small-scale tissue losses. In recent years, tissue engineering has been proposed as a promising alternative to tissue replacement with artificial grafts. According to this approach, biological engineered substitutes for tissue replacement are realized by seeding isolated autologous cells onto three-dimensional (3D) porous supports, termed scaffolds, and by guiding cell proliferation and differentiation in bioreactors, that provide the physiological pericellular environment for tissue development. The major issue for the realization of clinical-scale bioengineered substitutes for tissue replacement is the difficult supply of physiological amounts of dissolved oxygen and nutrients to, as well as metabolic wastes removal from, the cells located in the innermost regions of the 3D constructs (i.e. cell-seeded scaffolds). In particular, it is generally acknowledged that the severe consumption of dissolved oxygen by the cells represents the major limitation for cell survival in the development of bioengineered tissues. Static cultures in which dissolved oxygen and nutrients are supplied to the cells by pure diffusive transport have been shown to enable cell survival only to small-scale constructs. In order to overcome transport limitations of static cultures, dynamic bioreactors have been proposed in which a certain degree of convection is superimposed to pure diffusion to enable solutes transport towards, or away from, the innermost region of large-scale constructs. However, although some improvements over static cultures have been evidenced, dynamic bioreactors proposed so far, such as spinner flasks, rotating wall vessels and direct axial perfusion bioreactors, are still sub-optimal for the realization of clinical-scale bioengineered tissues. Recently, radial perfusion of hollow cylindrical 3D constructs in radial flow packed-bed bioreactors (rPBBs) has been proposed to overcome the limitations of both static and direct axial perfusion bioreactors, in particular for the development of bioengineered liver and bone tissues. In fact, since culture medium is perfused radially to the cells, shorter path lengths and larger cross-sectional areas for solutes transport are featured than those in axial flow bioreactors, that enable cell culture at small pressure drops and superficial velocities, and smoother solutes concentration gradients in the direction of the medium perfusion. Despite these promising features, design of rPBBs is more difficult than that of axial flow packed bed bioreactors. In fact, rPBBs require two void chambers (i.e. the inner hollow cavity and the peripheral annular space) to distribute and collect culture medium flowing across the construct thickness, the fluid dynamics of which may significantly influence radial flux distribution of culture medium along the construct length. Furthermore, the annular construct geometry and the direction of medium perfusion may strongly affect the transport of solutes towards, or from, the cells. The extent of the perfusion flow rates have also to be chosen in order to ensure adequate mass delivery to cells while preventing cell damage and washout. Mathematical models of transport in rPBBs may help optimize bioreactor design for a given application to enable dissolved oxygen and nutrients delivery towards, and metabolic wastes removal from, 3D clinical-scale constructs. However, a systematic analysis of the influence of all the geometrical, transport and operational dimensionless groups on bioreactor behavior aimed to design rPBBs so that solutes transport towards, or from, the cells is maximized and controlled has not been reported yet. This limits the exploitation of the peculiar features of the rPBBs in the development of bioengineered substitutes for tissue replacement. In this thesis, a model-based reference framework is proposed to optimize rPBB design to ensure adequate environmental conditions to cells for the realization of clinical-scale 3D bioengineered substitutes for tissue replacement. In particular, the attention is paid on transport of dissolved oxygen, since its limiting role for the realization of large-scale 3D biological constructs is generally acknowledged. In order to reach the proposed objective, the workflow was divided in three different steps, as follows: 1. A reference framework was first developed based on a one-dimensional stationary transport model, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics, to optimize annular construct geometry and direction and extent of the radial superficial velocity of the culture medium across the cell mass for the culture of largescale 3D porous constructs, assuming that radial flux distribution of the culture medium was uniform along the construct length. Dimensional analysis was used to find the dimensionless groups determining bioreactor behavior, under typical conditions for tissue engineering. In particular, according to this model, bioreactor behavior was shown to depend on the perfusion flow direction parameter, g; the dimensionless construct Darcy permeability, kL/R3; the inner hollow cavity radius-to-construct thickness ratio, R/dC; the maximal radial Peclet number, Perad,max; the Thiele modulus, fC; the saturation parameter, b. The effectiveness of oxygen supply to the cells was expressed in terms of the non-hypoxic fractional construct volume. Model predictions suggest that outward perfusion (i.e. form the construct inner surface towards the outer peripheral surface) of 3D annular porous constructs having small curvature (i.e., high inner hollow cavity radius-to-annular thickness ratio) at high perfusion flow rates, (i.e high maximal radial Peclet numbers) may enhance dissolved oxygen supply to the cells as compared to cell culture in static and axial flow bioreactors. 2. A design criterion to optimize rPBB design in order to achieve uniform radial flux distribution of the culture medium along the construct length was obtained, based on a two-dimensional stationary transport model of momentum in all the rPBB compartments (i.e. inner hollow cavity, porous construct, peripheral annulus), assuming that medium is perfused outwards according to the results obtained with the 1D model. In particular, momentum transport in the void spaces of the rPBB was described according to the Navier-Stokes equation, whereas Darcy-Brinkman equation was used to describe momentum transport in the porous construct. Dimensional analysis showed that the uniformity of radial flux distribution of the culture medium along the construct length depends on: a reduced Reynolds number, Rein; the construct aspect ratio, L/R; the inner hollow cavity radius-toconstruct thickness ratio, R/dC; the inner hollow cavity radius-to-peripheral annulus thickness ratio, R/dE; the construct-to-hollow cavity permeability ratio, k/R2. The influence of R/dC and R/dE was lumped in one dimensionless group (i.e. the hollow cavity-to-peripheral annulus cross-sectional area ratio, x), as suggested by literature results. The design criterion, termed CORFU (Criterion Of Radial Flux Uniformity), was shown to depend on all the dimensionless groups found by dimensional analysis. In particular, according to the CORFU criterion, uniform radial flux distribution of the culture medium along the construct length may be achieved by adjusting the values of the dimensionless groups determining rPBB behavior in order to ensure that the ratio between the total axial pressure drop in the void spaces is maintained within ±10% of the radial pressure drop across the construct. 3. The momentum transport model was integrated with a mass transport model to assess the actual effect of the radial flux distribution of the culture medium along the construct length on dissolved oxygen transport and to design rPBBs for a given therapeutic objective. Transport of dissolved oxygen in the construct was described in terms of the convection-diffusion-reaction equation, and dissolved oxygen consumption was described according to the Michaelis-Menten kinetics. Oxygen mass transfer coefficients accounting for the external mass transport at cell/medium interface were estimated for a bed of Raschig rings transport-equivalent to porous scaffolds adopted for tissue engineering. Dimensional analysis showed that, in addition to the dimensionless groups obtained for the momentum transport model previously listed, bioreactor behavior, which was expressed in terms of the Non-Hypoxic Fractional Construct Volume, depends on the following dimensionless groups: the maximal radial Peclet number, Perad,max; the construct-to-hollow cavity diffusivity ratio, DC/DH (and, analogously, the construct-to-peripheral annulus diffusivity ratio, DC/DE); the Sherwood number, Sh; the saturation parameter, b; the Thiele modulus, fC; the squared surface Thiele modulus-to-Sherwood number ratio, fs 2/Shp. The effect of the dimensionless number on bioreactor behavior was investigated under working conditions typical of tissue engineering. Model predictions suggested how to optimize bioreactor design in order to ensure controlled oxygen supply to cells for different tissue engineering applications. Medium radial flux distribution was shown to significantly influence oxygen spatial distribution inside the construct under conditions in which oxygen depletion is not properly compensated by oxygen supply to cells. The effect of medium radial flux distribution on oxygen supply becomes less important if oxygen consumption is compensated by oxygen supply. Model predictions also suggest that higher Rein influences oxygen spatial distribution from the top towards the bottom of the bioreactor for non-uniform medium radial flux distribution, giving higher uniformity of oxygen distribution along bioreactor length. The radial perfusion rates have to be optimized not only to control radial flux distribution, but also to enable adequate supply of dissolved oxygen to the cells while preventing cell wash out, at any given stage of tissue development. In particular, model predictions suggest that at the beginning of the culture medium flow rates may be kept low to avoid cell damage or wash out, whereas, as cells proliferate and differentiate, the medium flow rates should be gradually increased to balance out the increasing metabolic requirements of cells. In particular, higher perfusion flow rates enable more adequate oxygen supply to cells for a given value of fC. Finally, choosing perfusion rates that cause minimal Damköhler number, Darad,min = fC 2/Perad,max, to be small were shown to ensure adequate pericellular oxygenation (i.e. NHy-FCV around 1) for tissue development
Process design optimization based on metamodeling and metaheuristic techniques
(2015-12-16) Ciancio, Claudio; Pagnotta, Leonardo; Ambrogio, Giuseppina
This dissertation explores the use of mathematical and statistical tools to analyze, control and optimize manufacturing processes. Table 8.1 summarizes the topics analyzed and the contributions of this dissertation. The main topic discussed in this thesis is related to the features that have to be taken into account to select, according to the analyzed process: 1. the metamodel technique; 2. the sampling strategy; 3. the optimization algorithm All these problems were analyzed from two di erent point of views. Attacking the problems from a Computer Science angle has led to the development of a general version of the methodologies. In contrast, it is also crucial to analyze the process from a mechanical point of view trying to detect peculiarities that may simplify the computational e ort to solve the problem making use of the available knowledge. Chapter 2 provides a brief introduction of the most used approaches to de ne input-output relationships. It is pointed out that each technique is a ected by many limitations that could signi cantly a ect the accuracy of the model under certain conditions.Table 8.1: Dissertation Contributions. Chapter Theory Applications Chapter 1 Introduction, research statement and scope of the thesis Chapter 2 Machine learning techniques introduction Impression die forging Chapter 3 Heuristic technique to optimize neural network performance Extrusion, rolling and shearing Chapter 4 Kriging metamodel for mixed continuous/discrete problems Incremental sheet forming: thickness distributon Chapter 5 Manufacturing processes problem modeling Incremental sheet forming: temperature prediction Chapter 6 Adaptive KPI prediction based on response surface projection through similarity function Remote laser welding Chapter 7 Multi Objective Techniques. Development of a GDE3 based algorithm. Porthole extrusion Chapter 3 discusses the use of heuristic algorithms to solve these limitations. Di erent techniques were developed to improve the performance of a neural network metamodel. In particular three heuristics were developed and used to: 1. select the network architecture; 2. select the starting weights; 3. reduce the training time through an hybrid algorithm (simulated annealing+ backpropagation) Chapter 4 presents a novel kriging metamodel to solve problem characterized by both continuous and discrete variables. The model was coupled with a customized sampling strategy to reduce the number of experiments to reach a required accuracy. Typically, a speci c DoE method is most suitable in combination with each individual metamodel formulation. The proposed designs try to maximize a space- lling property. This feature assures a balanced predictive performance of the approximation model throughout the investigated model space. To collect training data e ciently, the locations for sampling points have to be chosen systematically thus assuring a maximum gain in information with minimal e ort. In particular the space lling criterion was considered only around a feasible region denoted as process window. Chapter 5 discuss the use of customized model based on prior knowledge of the process. According to that chapter 6 presents a new methodology with which a metamodel is developed making use of qualitative knowledge and/or historical data on similar problems. The metamodel try to iteratively develop new response surfaces through a geometrical projection based on a similarity function. Finally chapter 7 discuss the use of evolutionary algorithm to solve multi objective problems making use of the previous developed metamodel. To conclude, it is believed that this dissertation explores machine learning and optimization techniques for manufacturing from many angles, and that several of the ideas presented here will be useful both in practice and for theoretic studies
Advanced structural analyses of cable supported bridges
(2014-11-26) Pascuzzo, Arturo; Renato Sante Olivito, Renato Sante; Lonetti, Paolo
I ponti di grande luce sono strutture complesse che presentano un utilizzo ottimale dei materiali strutturali, caratteristiche estetiche e costruttive efficienti e bassi costi di manutenzione. A causa delle loro grandi dimensioni e delle diverse caratteristiche degli elementi strutturali, che sono essenzialmente la trave di irrigidimento, i piloni e il sistema dei cavi, i ponti di grande luce presentano diversi problemi che devono essere analizzati. Uno riguarda la definizione della configurazione iniziale della struttura. I ponti di grande luce, infatti, specialmente per lunghezze elevate, presentano un gran numero di cavi, che determinano strutture altamente iperstatiche. Come risultato, le forze di pretensione e le dimensioni delle sezioni trasversali dei cavi possono essere considerati come variabili di progetto che devono essere determinati. Un altro riguarda la valutazione della vulnerabilità strutturale nei riguardi di condizioni di carico estreme come il transito di carichi mobili o gli effetti prodotti da meccanismi di danneggiamento del sistema dei cavi, come la corrosione, che riducono fortemente l'integrità strutturale. Tali fenomeni producono significativi effetti di amplificazione dinamica in termini variabili tensionali e di spostamento. Tuttavia, gli effetti prodotti dall'azione dei carichi mobili o da meccanismi di danno non sono indipendenti. L’effetto della corrosione rende la struttura più sensibile all'azione di carichi mobili. D'altra parte, le vibrazioni indotte dal transito dei veicoli possono causare il deterioramento dei cavi per fatica o abrasione. Per queste ragioni, i problemi dei carichi mobili e dei meccanismi di danno dovrebbero essere studiati congiuntamente. L'ultimo è relativo agli effetti delle nonlinearità geometriche e dei materiali sul comportamento strutturale dei ponti. Le nonlinearità geometriche e dei materiali, infatti, influenzano la risposta dei ponti di grande luce e, di conseguenza, anche la massima capacità portante. Le nonlinearità dei materiali derivano dal legame sforzo-deformazione dei materiali, mentre le nonlinearità geometriche sono dovute all’effetto “sag” dei cavi, ai grandi spostamenti e ai fenomeni di interazione sforzo assiale-momento flettente che insorgono nella trave di irrigidimento e nei piloni (effetto beam-column). Obiettivo della presente tesi di dottorato è quello di sviluppare modelli strutturali avanzati per l’analisi delle problematiche dei ponti di grande luce precedentemente descritte. A tal fine, è si è fatto ricorso alla metodologia degli elementi finiti per riprodurre il comportamento strutturale dei principali ponti di grande luce. In particolare, è stata adottata una formulazione di tipo nonlineare geometrico, che ben si presta a riprodurre gli effetti delle vibrazioni locali dei cavi e i grandi spostamenti a cui sono soggetti la trave d’irrigidimento e i piloni. Per quanto riguarda la definizione della configurazione geometrica iniziale, viene elaborata una metodologia di progettazione per l’ottimizzazione delle forze di pretensione e per il dimensionamento delle sezioni trasversali dei cavi. La metodologia è data dalla combinazione del modello strutturale agli elementi finiti descritto in precedenza con una procedura di ottimizzazione iterativa. Tale procedura iterativa è utilizzata per ottimizzare la distribuzione delle forze di pretensione e le dimensioni delle sezioni trasversali al fine di minimizzare la quantità di acciaio e massimizzare le performance strutturali sotto l’azione di carichi di natura accidentale. In tale ambito, sono stati elaborati dei risultati per validare la metodologia proposta per mezzo di confronti con formulazioni presenti in letteratura. Inoltre, sono stati sviluppati risultati parametrici con riferimento a ponti di conformazione più complessa per verificare le regole di dimensionamento e per confrontare i ponti a configurazione mista sospesa strallata con le convenzionali configurazioni sospese e strallate. Inoltre, dettagliati risultati sono proposti con riferimento al caso dei ponti misti auto-ancorati sospesi strallati. Al fine di analizzare il comportamento strutturale di ponti di grande luce in presenza di meccanismi di danneggiamento del sistema dei cavi, sotto l’azione di carichi viaggianti, al modello agli elementi finiti sono aggiunte ulteriori formulazioni. In particolare, sono presi in considerazione gli effetti di accoppiamento flesso-torsionale della struttura da ponte e quelli associati ai contributi di carico e di massa derivanti dal sistema mobile. Inoltre, gli effetti di fenomeni di danneggiamento di elementi del sistema dei cavi, prodotti da preesistenti fenomeni di corrosione o rotture improvvise, vengono analizzati per mezzo di leggi esplicite in funzione del tempo, sviluppate nell’ambito della teoria della meccanica del danneggiamento. Inizialmente, le analisi hanno focalizzato l'attenzione sul comportamento dinamico di ponti strallati in presenza di rottura improvvisa di elementi costituenti il sistema dei cavi. In tale contesto sono proposti dei risultati ricavati da analisi sensitive delle variabili dei ponti di grande luce. In particolare, l’influenza dalle caratteristiche dei carichi mobili, delle tipologia dei piloni e dello scenario di danneggiamento sono studiati per mezzo di confronti tra configurazioni del ponte danneggiate e non danneggiate. Successivamente, viene analizzato il comportamento dei ponti misti strallati sospesi. E’ sviluppato uno studio parametrico sulla base di quattro scenari di danneggiamento che prevedono il danneggiamento degli stralli, dei pendini e del cavo principale. In particolare, al fine di evidenziare i vantaggi presentati dalla configurazione mista, vengono proposi dei risultati sotto forma di confronto con sistemi puri strallati e sospesi. I risultati sono espressi in termini di fattori di amplificazione dinamica delle tipiche variabili cinematiche e tensionali di progetto. Il problema della influenza sulla capacità massima di carico delle nonlinearità geometriche e del materiale è presentato con riferimento allo schema di sospensione strallato-sospeso auto-ancorato. Il comportamento non lineare del materiale della trave di irrigidimento e dei piloni è rappresentato da una raffinata formulazione agli elementi finiti che combina la teoria alla base del modulo tangente con un modello di cerniera plastica, mentre per i cavi viene adottata la teoria della plasticità per deformazioni finite. Nel quadro della non linearità geometrica, dal momento che il modello strutturale di base agli elementi finiti riproduce i grandi spostamenti e l’effetto "sag" dei cavi, che viene riprodotto per mezzo di un approccio multi truss element, sono agiunti ulteriori contributi per riprodurre l’effetto di interazione sforzo normalemomento flettente presente nelle pile e nella trave di irrigidimento. L'analisi si basa su un’analisi nonlineare al passo. Poiché il comportamento strutturale del ponte è fortemente influenzato dalle distribuzioni delle forze di pretensione del sistema dei cavi, come primo step viene determinata la configurazione geometrica iniziale del ponte sotto l'azione di carichi permanenti. I risultati sono finalizzati ad analizzare l'influenza sulla massima capacità di carico del comportamento nonlineare del materiale nonché dei parametri geometrici e strutturali.
Modelli e metodi di ottimizzazione nella progettazione, organizzazione e gestione dei Centri di Distribuzione
(2011) Simini, Maria; Musmanno, Roberto; Grandinetti, Lucio
Models and Policies for Service Industries via Revenue Management
(2011) Olivito, Filomena; Miglionico, Giovanna; Guerriero, Francesca; Grandinetti, Lucio

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