Two different aortic prostheses can be used for performing the Bentall procedure: a standard straight graft and the Valsalva graft that better reproduces the aortic root anatomy. The aim of the present work is to study the effect of the graft geometry on the blood flow when a bileaflet mechanical heart valve is used, as well as to evaluate the stress concentration near the suture line where the coronary arteries are connected to graft. An accurate three-dimensional numerical method is proposed, based on the immersed boundary technique. The method accounts for the interactions between the flow and the motion of the rigid leaflets and of the deformable aortic root, under physiological pulsatile conditions. The results show that the graft geometry only slightly influences the leaflets dynamics, while using the Valsalva graft the stress level near the coronary-root anastomoses is about half that obtained using the standard straight graft.

The simultaneous replacement of a diseased aortic valve, aortic root and ascending aorta with a composite graft equipped with a prosthetic valve is a nowadays standard surgical approach, known as the Bentall procedure: the Valsalva sinuses of the aortic root are sacrificed and the coronary arteries are reconnected directly to the graft. In practice, two different composite-material prostheses are largely used by surgeons: a standard straight graft and the Valsalva graft with a bulged portion that better reproduces the aortic root anatomy. The aim of the present investigation is to study the effect of the graft geometry on the the flowfield as well as on the stress concentration at the level of coronary-root anastomoses during the cardiac cycle. An accurate three-dimensional numerical method, based on the immersed boundary technique, is proposed to study the flow inside moving and deformable geometries. Direct numerical simulations of the flow inside the two prostheses, equipped with a bileaflet mechanical valve with curved leaflets, under physiological pulsatile inflow conditions show that, when using the Valsalva graft, the stress level near the coronary-root anastomoses is about half that obtained using the standard straight graft.

This work provides a three-dimensional energy optimization analysis, looking for perturbations inducing the largest energy growth at a finite time in a boundary-layer flow in the presence of roughness elements. The immersed boundary technique has been coupled with a Lagrangian optimization in a three-dimensional framework. Four roughness elements with different heights have been studied, inducing amplification mechanisms that bypass the asymptotical growth of Tollmien-Schlichting waves. The results show that even very small roughness elements, inducing only a weak deformation of the base flow, can strongly localize the optimal disturbance. Moreover, the highest value of the energy gain is obtained for a varicose perturbation. This result demonstrates the relevance of varicose instabilities for such a flow and shows a different behavior with respect to the secondary instability theory of boundary layer streaks.

This work provides a global optimization analysis, looking for perturbations inducing the largest energy growth at a finite time in a boundary-layer flow in the presence of smooth three-dimensional roughness elements. Amplification mechanisms are described which can bypass the asymptotical growth of Tollmien-Schlichting waves. Smooth axisymmetric roughness elements of different height have been studied, at different Reynolds numbers. The results show that even very small roughness elements, inducing only a weak deformation of the base flow, can localize the optimal disturbance characterizing the Blasius boundary-layer flow. Moreover, for large enough bump heights and Reynolds numbers, a strong amplification mechanism has been recovered, inducing an increase of several orders of magnitude of the energy gain with respect to the Blasius case. In particular, the highest value of the energy gain is obtained for an initial varicose perturbation, differently to what found for a streaky parallel flow. Optimal varicose perturbations grow very rapidly by transporting the strong wall-normal shear of the base flow, which is localized in the wake of the bump. Such optimal disturbances are found to lead to transition for initial energies and amplitudes considerably smaller than sinuous optimal ones, inducing hairpin vortices downstream of the roughness element.

This paper provides some recent developments of an immersed boundary method for solving flows of industrial interest at arbitrary Mach numbers. The method is based on the solution of the preconditioned compressible Favre-averaged Navier - Stokes equations closed by the k-ω low Reynolds number turbulence model. A flexible local grid refinement technique is implemented on parallel machines using a domain-decomposition approach and an edge-based data structure. Thanks to the efficient grid generation process, based on the ray-tracing technique, and the use of the METIS software, it is possible to obtain the partitioned grids to be assigned to each processor with a minimal effort by the user. This allows one to by-pass the very time consuming generation process of a body-fitted grid.

The purpose of these Lecture Series notes is to offer a full overview of the present development and the potential of the Large Eddy Simulation (LES) of turbulent flows. The first part of the course notes introduces and discusses fundamental principles, presents state-of-the-art applications and possible developments of LES and Detached Eddy Simulation (DES) which represents the most promising technique to extend the usefulness of LES for high Reynolds-number flows. The second part presents applications of these approaches to various engineering fields of wide interest. The course notes are written by internationally recognized experts. Its content is addressed both to researchers interested in the fundamental simulation of turbulence and engineers wanting to apply the LES technique or LES solvers to the accurate simulations of turbulent.

Explosive activity and lava dome collapse at stratovolcanoes can lead to pyroclastic density currents (PDCs; mixtures of volcanic gas, air, and volcanic particles) that produce complex deposits and pose a hazard to surrounding populations. Two-dimensional computer simulations of dilute PDCs (characterized by a turbulent suspended load and deposition through a bed load) show that PDC transport, deposition, and hazard potential are sensitive to the shape of the volcano slope (profile) down which they flow. We focus on three generic volcano profiles: straight, concave-upward, and convex-upward. Dilute PDCs that flow down a constant slope gradually decelerate over the simulated run-out distance (5 km in the horizontal direction) due to a combination of sedimentation, which reduces the density of the PDC, and mixing with the atmosphere. However, dilute PDCs down a concave-upward slope accelerate high on the volcano flanks and have less sedimentation until they begin to decelerate over the shallow lower slopes. A convex-upward slope causes dilute PDCs to lose relatively more of their pyroclast load on the upper slopes of a volcano, and although they accelerate as they reach the lower, steeper slopes, the acceleration is reduced because of the upstream loss of pyroclasts (lower density contrast with the atmosphere). Dynamic pressure, a measure of the damage that can be caused by PDCs, reflects these complex relations.

The simultaneous replacement of a diseased aortic valve, aortic root and ascending aorta with a prosthesis is known as Bentall procedure (Bentall and De Bono in Thorax 23:338, 1968). This is a nowadays standard surgical approach in which the Valsalva sinuses of the aortic root are sacrificed and the coronary arteries are reconnected directly to the graft. The important function of the natural sinuses in the presence of the natural valve is well established; however, very little information is available about whether or not their presence can affect the functioning of a prosthetic hi-leaflet valve and the coronary flow. In the present work, we study the effect of the aortic root geometry on the blood flow through such devices, focusing the attention on the coronary entry-flow. Three root geometries have been considered, two mimicking the prostheses used in practice by surgeons (a straight tube, and the more recent tube with a circular pseudo-sinus), and a third maintaining the natural shape with three sinuses, Obtained by Reul et al. (J Biomech 23:181-191, 1990) by averaging numerous angiographies of the aortic root in healthy patients. Direct numerical simulations of the flow inside the three prostheses, assumed as undeformable, under physiological pulsatile inflow conditions are presented. The dynamics of the valvular leaflets is obtained by a fully-coupled fluid structure-interaction approach and the coronary perfusion is reproduced by modulating in time an equivalent porosity, an thus the resistance, of the coronary channels. The results indicate that the sinuses do not significantly influence the coronary entry flow, in agreement with the in vivo observations of De Paulis et al. (Eur J Cardio-thorac Surg 26:66-72, 2004). Nevertheless, the peak pressure at the joints of the coronary arteries is smaller in the natural-like aortic root geometry. The latter also produces a further beneficial effect of a reduction in the leaflets' angular velocity at the closure onto the valvular ring. These phenomena, if confirmed in more realistic clinical conditions, suggest that the use of a prothesis with physiologic sinuses would potentially reduce the local pressure peak, with the associated risk of post-operative bleeding and pseudo-aneurysm formation. It would also reduce the haemolysis effects caused by the red blood cells squashing between impacting solid artificial surfaces.

This paper provides some recent results obtained in the development of Immersed Boundary (IB) methods at the Politecnico di Bari: in particular, the development and testing of one such method—using a versatile Moving Least Squares approach, coupled with a very efficient solver for solving fluid-structure interaction problems in incompressible laminar flows—will be addressed. Such a method allows one to solve complex three-dimensional solid-fluid interaction problems within reasonable computer times. The solver is validated versus: the free fall of a sphere within a fluid at rest and jellyfish propulsion. Such results demonstrate the accuracy, efficiency, and versatility of the proposed method.

The paper reports the prediction of mechanical hemolysis by three different models for the case of blood flow through aortic valved prostheses. Two of the adopted models are based on the action of instantaneous shear stress on the blood cells (stress-based), while the third accounts for the finite response time of cell deformation and relaxation (strain-based). Two aortic Dacron grafts commonly adopted in clinical practice are considered, and both are equipped with a bileaflet mechanical valve. One of the grafts reproduces the three sinuses of Valsalva, while the other is a straight tube. A direct numerical simulation approach is utilized to solve the complex fluid-structure-interaction problem and obtain detailed information of the flow patterns. To evaluate hemolysis, a large number of Lagrangian tracer particles were released at the inlet of the computational domain (upstream of the valve), and blood damage was evaluated along each trajectory for each model. We found that stress-based models predict higher levels of blood damage than the strain-based one. The same level of blood damage is observed in the two geometric configurations we considered, indicating that the adopted mechanical valve is primary risk factor for hemolysis.

Pyroclastic density currents are ground hugging, hot, gas-particle flows representing the most hazardous events of explosive volcanism. Their impact on structures is a function of dynamic pressure, which expresses the lateral load that such currents exert over buildings. Several critical issues arise in the numerical simulation of such flows, which involve a rheologically complex fluid that evolves over a wide range of turbulence scales, and moves over a complex topography. In this paper we consider a numerical technique that aims to cope with the difficulties encountered in the domain discretization when an adequate resolution in the regions of interest is required. Without resorting to time-consuming body-fitted grid generation approaches, we use Cartesian grids locally refined near the ground surface and the volcanic vent in order to reconstruct the steep velocity and particle concentration gradients. The grid generation process is carried out by an efficient and automatic tool, regardless of the geometric complexity. We show how analog experiments can be matched with numerical simulations for capturing the essential physics of the multiphase flow, obtaining calculated values of dynamic pressure in reasonable agreement with the experimental measurements. These outcomes encourage future application of the method for the assessment of the impact of pyroclastic density currents at the natural scale.

Vascular targeted nanoparticles have been developed for the delivery of therapeutic and imaging agents in cancer and cardiovascular diseases. However, at authors' knowledge, a comprehensive systematic analysis on their delivery efficiency is still missing. Here, a computational model is developed to predict the vesselwall accumulation of agents released from vascular targeted nanoconstructs. The transport problem for the released agent is solved using a finite volume scheme in terms of three governing parameters: the local wall shear rate S, ranging from 10 to 200 s-1; the wall filtration velocity Vf , varying from 10-9 to 10-7 m/s; and the agent diffusion coefficient D, ranging from 10-12 to 10 -9 m2/s. It is shown that the percentage of released agent adsorbing on the vessel walls in the vicinity of the vascular targeted nanoconstructs reduces with an increase in shear rate S, and with a decrease in filtration velocity Vf and agent diffusivity D. In particular, in tumor microvessels, characterized by lower shear rates (S = 10 s-1) and higher filtration velocities (Vf = 10-7 m/s), an agent with a diffusivity D = 10-12 m2/s (i.e. a 50nm particle) is predicted to deposit on the vessel wall up to 30 % of the total released dose. Differently, drug molecules, exhibiting a smaller size and much higher diffusion coefficient (D = 10-9 m2/s), are predicted to accumulate up to 70 %. In healthy vessels, characterized by higher S and lower Vf , the largest majority of the released agent is redistributed directly in the circulation. These data suggest that drug molecules and small nanoparticles only can be efficiently released from vascular targeted nanoconstructs towards the diseased vessel walls and tissue.

Dust storms are common in arid and semi-arid regions, e.g., the Arabian Peninsula, where undisturbed wind can either weather the rocks and transport the grains for kilometers over the landscape or even overseas, or form dunes and ripples. We used a multiphase Eulerian–Lagrangian computational fluid dynamics model to investigate the impact of dust storms in the form of density current on a 10 × 10-m building. This numerical investigation particularly applies to the suburbs of metropolis, consisting of peripheral neighborhoods of meter-scale buildings that, as suggested by our results, can strongly affect the path of the storm before impacting the Downtown. Our results of flow-building interaction on pulsating (CASE 1) versus sustained (CASE 2, reference) and long-lived (CASE 3) storm show a strong amplification of flow dynamic pressure up to a factor of about 14 in streamwise direction and a heavy grain accumulation of about 800 kg around the building. With respect to reference sustained storm, the results show a more intense pressure amplification up to about 12 for slower (CASE 4) or coarser (CASE 5) storm, but a less intense amplification up to about 3 for more dilute storm (CASE 6) in transverse direction. Maximum grain accumulation around the building is of about 4,300 kg (55 % is on building front) for coarser storm, whereas high fog in the building rear occurs for more dilute storm. These results can be useful when assessing the impact of dust storms against buildings.

The in vivo evaluation of prosthetic device performance is often difficult, if not impossible. In particular, in order to deal with potential problems such as thrombosis, haemolysis, etc., which could arise when a patient undergoes heart valve replacement, a thorough understanding of the blood flow dynamics inside the devices interacting with natural or composite tissues is required. Numerical simulation, combining both computational fluid and structure dynamics, could provide detailed information on such complex problems. In this work, a numerical investigation of the mechanics of two composite aortic prostheses during a cardiac cycle is presented. The numerical tool presented is able to reproduce accurately the flow and structure dynamics of the prostheses. The analysis shows that the vortical structures forming inside the two different grafts do not influence the kinematics of a bileaflet valve or the main coronary flow, whereas major differences are present for the stress status near the suture line of the coronaries to the prostheses. The results are in agreement with in vitro and in vivo observations found in literature.

A large number of studies document the strong expression of aquaporin-1 (AQP1) in tumor microvessels and correlate this aberrant expression with higher metastatic potential and aggressiveness of the malignancy. Although small animal experiments have shown that the modulation of AQP1 expression can halt angiogenesis and induce tumor regression, effective and safe strategies for the tissue specific inhibition of AQP1 are still missing. Here, small interference RNA-chitosan complexes encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are proposed for the intracellular delivery of siRNA molecules against AQP1. These NPs are coated with poly(vinyl alcohol) (PVA), to improve stability under physiological conditions, and demonstrate a diameter of 160 nm. The partial neutralization of the negatively charged siRNA molecules with the cationic chitosan enhances the loading by 5-fold, as compared to that of the free siRNA molecules, and allows one to modulate the release kinetics in the pH-dependent manner. At pH = 7.4, mimicking the conditions found in the systemic circulation, only the 40% of siRNA is released at 24 h post incubation; whereas at pH = 5.0, recreating the cell endosomal environment, all siRNA molecules are released in about 3 h. These NPs show no cytotoxicity on HeLa cells up to 72 h of incubation. In the same cells, transfected to overexpress AQP1, a silencing efficiency of 70% is achieved at 24 h post treatment with siRNA-loaded NPs. Confocal microscopy analysis of NP uptake demonstrates that siRNA molecules accumulate perinuclearly and in the nucleus. Given the stability, preferential release behavior, and well-known biocompatibility properties of PLGA nanostructures, these siRNA-loaded NPs hold potential for the efficient and safe in vivo silencing of AQPs via systemic administration.

Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200. nm to 1800. nm. The fabrication process of the mesoporous particles is described in detail, and their transport and adhesion properties under flow are studied using a parallel plate flow chamber. Numerical simulations predict the hydrodynamic forces on the particles and help in interpreting their distinctive behaviors. Under microvascular flow conditions, for disk-like shape, 1000. ×. 400. nm particles show maximum adhesion, whereas smaller (600. ×. 200. nm) and larger (1800. ×. 600. nm) particles adhere less by a factor of about two. Larger rods (1800. ×. 400. nm) are observed to adhere at least 3 times more than smaller ones (1500. ×. 200. nm). For particles of equal volumes, disks adhere about 2 times more than rods. Maximum adhesion for intermediate sized disks reflects the balance between adhesive interfacial interactions and hydrodynamic dislodging forces. In view of the growing evidence on vascular molecular heterogeneity, the present data suggests that thin disk-like particles could more effectively target the diseased microvasculature as compared to spheres and slender rods.