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An innovative approach to simulate thrombosis with smoothed particle hydrodynamics
Full text linkLa trombosi è una patologia che porta alla formazione di coaguli, che possono provocare ostruzioni arteriose e, infine, migrano attraverso il sistema cardiocircolatorio causando infarto, ictus o embolia polmonare. Il processo è abbastanza complesso ed il suo meccanismo non è ancora chiaro, essendo il risultato dell’interazione tra diversi fattori, compresa l'attivazione e l'aggregazione piastrinica, le reazioni chimiche e l'emodinamica.È fondamentale considerare e ridurre al minimo la formazione di trombi nella progettazione e realizzazione di organi artificiali, come valvole cardiache artificiali o protesi. Lo studio dell'emodinamica può fornire un supporto efficace per identificare e prevenire il rischio di trombosi.A causa della mancanza di soluzioni analitiche adeguate e della complessità degli studi sperimentali, la ricerca evolve sempre più verso l’utilizzo delle simulazioni numeriche Questa tesi mira a modellare la formazione, la crescita e l'evoluzione del trombo mediante il metodo numerico accoppiato Smoothed Particle Hydrodynamics (SPH) usando un modello di interazione fluido-struttura (FSI). Il modello proposto descrive le principali fasi della cascata coagulativa attraverso l'equilibrio di quattro specie biochimiche e tre tipologie di piastrine. Le particelle SPH possono passare dalla fase fluida a quella solida se sono soddisfatte delle specifiche condizioni biochimiche e fisiche. L'accoppiamento fluido-solido è modellato introducendo legami elastici tra le particelle solide senza nessuna interfaccia. Per raggiungere questo obiettivo, in primo luogo il modello viene validato confrontando i risultati numerici con i dati sperimentali disponibili in letteratura, in secondo luogo, il nuovo codice numerico è applicato per descrivere la trombosi in appendice atriale in caso di fibrillazione o come trombosi indotta in aneurismi cerebrali.Thrombosis is a pathology leading to the formation of clots, that can result in arterial obstructions and, eventually, migrate through the cardiocirculatory system causing heart attack, stroke or pulmonary embolism. The process is complex and its mechanism is still unclear, being the result of the interaction between various factors, including platelet activation and aggregation, chemical reactions, and hemodynamics.It is crucial to consider and minimise thrombosis in the design and implementation of artificial organs, such as artificial heart valves, and vascular prostheses. The study of hemodynamics can provide effective support to identify and prevent the risk of thrombosis.Due to the lack of adequate analytical solutions and the complexity of experimental studies, research increasingly evolves towards the use of computational methods.This thesis aims at modelling the formation, growth and evolution of thrombus by means of a Smoothed Particle Hydrodynamics (SPH) numerical method coupled with a fluid-structure interaction (FSI) model. The proposed model describes the main phases of the coagulative cascade through the balance of four biochemical species and three types of platelets. SPH particles can switch from fluid to solid phase whenspecific biochemical and physical conditions are satisfied. Fluid-solid coupling is modelled by introducing elastic binds between solid particles, without requiring detention and management of the interface between the two media.In order to reach this goal, firstly the model is validated by comparing the numerical prediction with experimental data available in the literature, secondly, it is applied to describe thrombosis formation due to relevant pathologies such as atrial fibrillation and cerebral aneurysms where the insertion of flow diverter creates thrombogenic stasis zone
Theoretical and numerical analysis of the flow through a diffuser/nozzle element in pulsatile laminar conditions
Full text linkDiffusion of floating particles in open channel flow through emergent vegetation
Full text linkIn this thesis we study the problem of the dispersion of floating particles within emergent vegetation through experimental, numerical and theoretical analysis of the mechanisms that rule their temporary retention and the
capture by plants.
In Chapter 1 we present early results of laboratory experiments performed to investigate the transport and the diffusion of floating particles e.g., buoyant seeds) in open channel flow with emergent vegetation. The experiments are aimed at providing a better understanding of the relevant
particle-vegetation interaction mechanisms responsible for the observed diffusion processes.
Qualitative observational data are then used to set up a stochastic model for floating particle transport and diffusion. Quantitative observations, such as the distribution of distances travelled by a particle before it is permanently captured by a plant (resembled spartina maritima) and the arrival
time distributions at prescribed cross sections along the vegetated test section, are instead used to calibrate and validate the model. The comparison between theoretical predictions and experimental results is quite satisfactory
and suggests that the observed relevant aspects of the particle-vegetation interaction processes are properly described in the model.
In Chapter 2 we present the results of a new laboratory investigation aimed at providing a better understanding of the transport and diffusion processes. The experiments are designed primarily to study the influence of vegetation density and flow velocity on the relevant interaction mechanisms between particles and vegetation. The aim is also to ascertain the validity of the stochastic model proposed in Chapter 1.
We find that i) the proper definition of plant spacing is given as 1/npdp, dp being the plant diameter and np the number of plants per unit area; ii) the particle retention time distribution can be approximated by a weighted combination of two exponential distributions; iii) flow velocity has a significant
influence on the retention time and on the efficiency of the different trapping mechanisms, iv) vegetation pattern and density have a minor or negligible influence on the capture probability and on the retention time.
In the first part of Chapter 3 we study, in details, through a numerical model, the dynamics of capture due to surface tension (i.e. the Cheerios effect) of a cylindrical collector. The analysis shows that when capillary force is comparable to inertial forces the capture efficiency of the collector
increases significantly with respect to the non-floating particle.
In the second part of Chapter 3, instead, we propose, and verify through laboratory experiments, some improvements to the model described in Chapter 1. In this case the emergent vegetation is simulated with an array of cylinders,
randomly arranged, with the mean gap between cylinders far greater than the particle size, so to prevent the trapping of particles between pairs of cylinders, referred to as net trapping in Chapter 1. A good agreement
is found also when comparing the model prediction with experimental data available in the literature for real seeds and more complex plant morphology.In questa tesi è stato studiato il problema della dispersione di particelle galleggianti in presenza di vegetazione emergente per mezzo di analisi sperimentali, numeriche e teoriche dei meccanismi che ne governano la ritenzione
temporanea e la cattura da parte delle piante.
Nel Capitolo 1 sono presentati i risultati delle prove di laboratorio effettuate per indagare il trasporto e la diffusione di particelle galleggiati (ad esempio alcune varietà di semi) in un canale con vegetazione emergente. Questi esperimenti sono stati svolti per fornire una comprensione più ampia
dei principali processi di interazione particella-pianta responsabili del processo diffussivo osservato. Queste osservazioni qualitative sono state successivamente utilizzate per mettere a punto un modello stocastico per il trasporto e la diffusione di particelle galleggianti. Ulteriori dati raccolti sperimentalmente, quali la distribuzione delle distanze percorse dalle particelle prima di essere catturate permanentemente dalle piante e la distribuzione dei tempi di arrivo in alcune specifiche sezioni del tratto vegetato utilizzato nelle prove sperimentali, sono invece stati utilizzati per la calibrazione e la validazione del modello. Il confronto
tra i risultati forniti dal modello e quelli sperimentali è soddisfacente e suggerisce che gli aspetti più rilevanti osservati nei processi di interazione particella-vegetazione sono opportunamente descritti dal modello.
Nel Capitolo 2 sono presentati i risultati di nuove prove sperimentali effettuate per approfondire la conoscenza dei processi di trasporto e di diffusione. In questo caso le prove sono state realizzate per valutare l’influenza della densità della vegetazione e della velocità della corrente sui meccanismi di interazione precedentemente individuati. I risultati, infine, sono stati utilizzati per confermare la validità del modello proposto nel Capitolo 1.
E' stato trovato che i) la definizione più corretta di interasse tra le piante è 1/npdp, dp, essendo dp il diametro della pianta e np il numero di piante per unità d’area, ii) la distribuzione dei tempi di ritenzione delle particelle può essere approssimato da una combinazione di due distribuzioni esponenziali opportunamente pesate, iii) la velocità della corrente ha un forte impatto sui tempi di ritenzione e sull'efficacia dei differenti meccanismi di cattura,
mentre iv) la distribuzione e la densità della vegetazione gioca un ruolo di minor rilievo, se non addirittura trascurabile, sulla probabilità di cattura e sui tempi di ritenzione.
Nella prima parte del Capitolo 3 è studiata nel dettaglio la dinamica di cattura di un collettore cilindrico dovuta alla tensione superficiale (cioè l’effetto Cheerios). Lo studio mostra che, quando la forza capillare è comparabile alle forze inerziali, l’efficienza di cattura del collettore aumenta
significativamente rispetto al caso in cui le particelle siano non galleggianti.
Nella seconda parte del Capitolo 3, invece, sono proposte e verificate attraverso prove di laboratorio, alcune migliorie al modello introdotto nel Capitolo 1. In questo caso la vegetazione emergente è simulata da una
schiera di cilindri, disposti casualmente, e distanziati tra loro in modo tale che le particelle non possano essere soggette alla cattura dovuta ad una coppia di cilindri e definita net trapping nel corso del Capitolo 1. Una buona
corrispondenza è stata trovata anche quando i risultati forniti dal modello sono stati confrontati con alcuni dati sperimentali reperiti in letteratura relativi a semi reali ed a piante aventi una morfologia più complessa
TRASPORTO E DIFFUSIONE DI PARTICELLE GALLEGGIANTI IN CANALI VEGETATI IN PRESENZA DI VEGETAZIONE EMERSA
No full textIn questo lavoro si propone un semplice modello stocastico del trasporto e della diffusione di piccole particelle galleggianti in una corrente a superficie libera in presenza di vegetazione parzialmente emersa. Il modello, che si basa sull’osservazione sperimentale dei processi di interazione particelle-vegetazione, sintetizza in modo concettualizzato i principali meccanismi che influenzano la propagazione delle particelle galleggianti.
Le previsioni del modello proposto sono quindi confrontate con i risultati di alcune indagini sperimentali condotte in una canaletta di laboratorio attrezzata con vegetazione sintetica. Dal confronto emerge un sostanziale accordo tra le previsioni teoriche e le risultanze sperimentali a confermare l’efficacia del modello e la correttezza con cui sono rappresentati i diversi meccanismi di interazione osservati
Diffusion in floating particles in flow through emergent vegetation: Further experimental investigations
No full textIn this paper we present the results of a new laboratory
investigation aimed at providing a better understanding of the
transport and diffusion processes of floating particles (e.g.,
buoyant seeds) in open channel flow with emergent vegetation. The
experiments are designed primarily to study the influence of
vegetation density and flow velocity on the relevant interaction
mechanisms between particles and vegetation. The aim is also to
ascertain the validity of a stochastic model recently proposed by Defina and Peruzzo [2010].
We find that i) the proper definition of plant spacing is given
as 1/np dp, dp being the plant diameter, np the number
of plants per unit area; ii) the particle retention time
distribution can be satisfactorily approximated by a weighted
combination of two exponential distributions; iii) flow velocity
has a significant influence on the retention time and on the
efficiency of the different trapping mechanisms, and iv)
vegetation pattern and density have a minor influence on the
probability of capture and on the retention time of particles}.
Indeed, the comparison between model predictions and experimental
results is satisfactory and suggests that the observed relevant
aspects of the particle-vegetation interaction processes are
properly described by the model
Metabolic alterations and mitochondrial bioenergetic profile in HDAC4-driven tumorigenesis
Full text linkMany tumors display a high rate of glycolysis and lactate secretion even in presence of ample oxygen concentrations and a reduced rate of aerobic respiration - the so called Warburg effect. Nevertheless, most tumor mitochondria are not defective in their ability to carry out oxidative phosphorylation. Previous experiments demonstrated that NIH-3T3 murine fibroblasts expressing the TM mutant of class IIa HDAC4, which has an almost total nuclear subcellular localization and therefore acts as a "super-repressive" form of HDAC4, are capable, unlike the WT counterpart, to grow in anchorage-independent way in-vitro and to form tumors in mice. The aim of this thesis is to characterize the tumoral metabolic phenotype of HDAC4TM-expressing cells. Although HDAC4TM-expressing cells had a proliferative advantage with respect to control cells, they did not lower the pH of the medium. In accordance, HDAC4TM cells lactate secretion, taken as a marker of glycolytic metabolism, was comparable with their counterpart cells and the inhibition of LDHa was able to discriminate between HDAC4TM- and H-RASG12V-expressing tumorigenic control cells which displayed a classic Warburg phenotype. However, HDAC4TM-expressing cells showed higher glucose shortage sensibility and a lower 2-DG IC50 compared to control cells, indicating a glycolysis dependance of HDAC4TM-expressing cells in between that of H-RASG12V-expressing cells and non-tumorigenic cells. In contrast to H-RASG12V cells, short-term blockade of glycolysis in HDAC4TM-expressing cells affected ATP production in a manner undistinguishable from control cells, while long-term glycolysis inhibition differentially impacted H-RASG12V and HDAC4TM tumorigenic potential. High resolution respirometry showed, in sharp contrast with H-RASG12V cells, a slight increase in basal mitochondrial oxygen consumption rate of HDAC4TM cells with respect to control cells, without affecting mitochondrial mass or membrane potential, that can be in part accounted for a slightly higher ETS complex I activity. OXPHOS inhibition did not cause a dramatic drop in intracellular ATP levels even though was sufficient to abolish HDAC4TM proliferative advantage with respect to cotrol cells. Surprisingly, however, OXPHOS inhibition revealed a less pronounced effect on HDAC4TM than on H-RASG12V tumorigenic potential. These results seem to support a model in which, despite a tumorigenic potential similar to H-RASG12V cells, the augmented glycolytic flux of HDAC4TM cells is not coupled to lactate secretion because of the preservation of mitochondrial compartment functionality but is speculatively used to increase the pool of metabolic intermediates needed for sustained cell proliferation
Floating particle trapping and diffusion in vegetated open channel flow
Full text linkIn this paper we present early results of laboratory experiments to investigate the
transport and diffusion of floating particles (e.g., buoyant seeds) in open channel flow
with emergent vegetation. The experiments are aimed at providing a better understanding
of the relevant particle‐vegetation interaction mechanisms responsible for the observed
diffusion processes. Qualitative observational data are then used to set up a stochastic
model for floating particle transport and diffusion. Quantitative observations, such as the
distribution of distances travelled by a particle before it is permanently captured by a plant
and the arrival‐time distributions at prescribed cross sections along the vegetated test
section, are instead used to calibrate and validate the model. The comparison between
theoretical predictions and experimental results is quite satisfactory and suggests that the
observed relevant aspects of the particle‐vegetation interaction processes are properly
described in the model
Limb ischemia prevention: an open problem explored by computational fluid dynamics
No full textLimb ischemia has a high incidence (10-30%) in patients supported by peripheral Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO), negatively impacting long-term functional outcomes and survival. In recent years, bidirectional flow cannulae have shown promise as a solution to ensure distal limb perfusion, potentially eliminating the need for additional interventions. However, concerns remain about their local effects on haemodynamics close to the cannula insertion.
We compared by numerical simulation the flow field in an idealised artery-cannula district considering three designs of cannula. All configurations are based on a standard cannula of 21Fr with three different geometries of the elbow. Cannula A has the one-directional standard configuration, while Cannula B and C include one and four secondary holes, respectively, as indicated in two published patents. To evaluate the efficacy of the new cannulae, we applied the same operative conditions. Specifically, a pressure of 0mmHg is applied at the distal and proximal extremities of the artery, and a flow condition of 1.4L/min is applied at the cannula inlet.
The results show that Cannula B and C increase the distal limb perfusion. The secondary holes provide a flow of 0.32L/min and 0.56L/min, respectively. Furthermore, the numerical simulations evidence potential risks related to shear stress distribution in design A and C, displaying extended regions with low wall shear stress, WSS<0.4Pa. This condition favours clot formation and abnormal response of the wall.
The presented numerical simulations partially confirm the efficacy of new return cannula as an alternative to the standard techniques
Metabolic alterations and mitochondrial bioenergetic profile in HDAC4-driven tumorigenesis
No full textThe importance of hemodynamics in stented vessels: A conceptual model for predicting restenosis using the time-averaged shear stress
Full text linkThe role of hemodynamics has often been overlooked in mathematical modeling aimed at replicating the restenosis process in stented arteries. This study seeks to address this gap by proposing a simplified model of tissue growth driven by the distribution of mean shear stress acting on the vessel wall. Using an iterative sequence of three-dimensional Computational Fluid Dynamics simulations applied to idealized coronary and femoral arteries, combined with a semi-empirical parametrization of endothelium growth, we demonstrated that the progression of restenosis can be effectively modeled and differentiated according to the intensity of time-varying flow velocities. Notably, restenosis develops faster in the femoral artery (approximately 17 days) compared to the coronary artery (approximately 25 days). The progress of tissue accretion is well defined by the evolution of time-averaged wall shear stress. After an initial decrease (triggering phase), significant increases in wall shear stress..
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