High-fidelity modelling and feedback control of bio-inspired membrane wings

This work is a numerical investigation on the performance of integrally actuated two-dimensional membrane wings made with dielectric elastomers. A high-fidelity model based on the direct numerical integration of the unsteady Navier-Stokes equations is coupled with a geometrically non-linear structural model. The rate-dependent constitutive law for the dielectric elastomer is based on a non-linear formulation, and it has been validated against experimental data. In addition, the implementation of the aeroelastic framework has been verified against the relevant literature for the low-Reynolds number flows investigated in this dissertation. Numerical simulations of the open-loop dynamics of the actuated membrane, in good agreement with experimental observations, show that integral actuation offers enough authority in the control of the wing aerodynamic performance. Dielectric elastomers can then be used as embedded actuators, coupling the advantages of passive membranes with a simple and lightweight control mechanism. Further, this work also proposes a model-reduction methodology for the fully coupled system to aid control system design. The low-order description of the actuated system can capture the main system dynamics, and can be used for the design of the control scheme of the wing. Proportional-Integral-Derivative and Linear Quadratic Gaussian feedback controllers, designed using the reduced-order model, are finally implemented in the high-fidelity model for the rejection of flow disturbances. Results show that the wing aerodynamic performance is noticeably enhanced through the actuation as the disturbances on the lift in case of gusts can be reduced up to 60%.Open Acces

Stabilized reduced-order models for unsteady incompressible flows in three-dimensional parametrized domains

In this work we derive a parametric reduced-order model (ROM) for the unsteady three-dimensional incompressible Navier–Stokes equations without additional pre-processing on the reduced-order subspaces. Concerning the high-fidelity, full-order model, we start from a streamline-upwind Petrov–Galerkin stabilized finite element discretization of the equations using elements for velocity and pressure, respectively. We rely on Galerkin projection of the discretized equations onto reduced basis subspaces for the velocity and the pressure, respectively, obtained through Proper Orthogonal Decomposition on a dataset of snapshots of the full-order model. Both nonlinear and nonaffinely parametrized algebraic operators of the reduced-order system of nonlinear equations, including the projection of the stabilization terms, are efficiently assembled exploiting the Discrete Empirical Interpolation Method (DEIM), and its matrix version (MDEIM), thus obtaining an efficient offline–online computational splitting. We apply the proposed method to (i) a two-dimensional lid-driven cavity flow problem, considering the Reynolds number as parameter, and (ii) a three-dimensional pulsatile flow in stenotic vessels characterized by geometric and physiological parameter variations. We numerically show that the projection of the stabilization terms on the reduced basis subspace and their reconstruction using (M)DEIM allows to obtain a stable ROM with coupled velocity and pressure solutions, without any need for enriching the reduced velocity space, or further stabilizing the ROM. Additionally, we demonstrate that our implementation allows to compute the ROM solution about 20 times faster than the full order model

Propagation of Plasma L-Phenylalanine Concentration Fluctuations to the Neurovascular Unit in Phenylketonuria: An in silico Study

Phenylketonuria (PKU) is an inherited metabolic disease characterized by abnormally high concentrations of the essential amino acid L-phenylalanine (Phe) in blood plasma caused by reduced activity of phenylalanine hydroxylase (PAH). While numerous studies have shown association between high plasma Phe concentration and intellectual impairment, it is not clear whether increased Phe fluctuations also observed in PKU affect the brain as well. To investigate this, time-resolved in vivo data on Phe and competing large neutral amino acid (LNAA) concentrations in neurons are needed, but cannot be acquired readily with current methods. We have used in silico modeling as an alternative approach to characterize the interactive dynamics of Phe and competing LNAAs (CL) in the neurovascular unit (NVU). Our results suggest that plasma Phe fluctuations can propagate into the NVU cells and change there the concentration of LNAAs, with the highest magnitude of this effect observed at low frequency and high amplitude-to-mean ratio of the plasma Phe concentration fluctuations. Our model further elucidates the effect of therapeutic LNAA supplementation in PKU, showing how abnormal concentrations of Phe and CL in the NVU move thereby toward normal physiologic levels

Septaly Oriented Mild Aortic Regurgitant Jets Negatively Influence Left Ventricular Blood Flow—Insights From 4D Flow MRI Animal Study

Objectives: Paravalvular leakage (PVL) and eccentric aortic regurgitation remain a major clinical concern in patients receiving transcatheter aortic valve replacement (TAVR), and regurgitant volume remains the main readout parameter in clinical assessment. In this work we investigate the effect of jet origin and trajectory of mild aortic regurgitation on left ventricular hemodynamics in a porcine model. Methods: A pig model of mild aortic regurgitation/PVL was established by transcatheter piercing and dilating the non-coronary (NCC) or right coronary cusp (RCC) of the aortic valve close to the valve annulus. The interaction between regurgitant blood and LV hemodynamics was assessed by 4D flow cardiovascular MRI. Results: Six RCC, six NCC, and two control animals were included in the study and with one dropout in the NCC group, the success rate of model creation was 93%. Regurgitant jets originating from NCC were directed along the ventricular side of the anterior mitral leaflet and integrated well into the diastolic vortex forming in the left ventricular outflow tract. However, jets from the RCC were orientated along the septum colliding with flow within the vortex, and progressing down to the apex. As a consequence, the presence as well as the area of the vortex was reduced at the site of impact compared to the NCC group. Impairment of vortex formation was localized to the area of impact and not the entire vortex ring. Blood from the NCC jet was largely ejected during the following systole, whereas ejection of large portion of RCC blood was protracted. Conclusions: Even for mild regurgitation, origin and trajectory of the regurgitant jet does cause a different effect on LV hemodynamics. Septaly oriented jets originating from RCC collide with the diastolic vortex, reduce its size, and reach the apical region of the left ventricle where blood resides extendedly. Hence, RCC jets display hemodynamic features which may have a potential negative impact on the long-term burden to the heart

Conformational altered p53 as an early marker of oxidative stress in Alzheimer\u27s disease

In order to study oxidative stress in peripheral cells of Alzheimer\u27s disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named unfolded p53 , was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients

Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named “unfolded p53”, was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients

Personalising left-ventricular biophysical models of the heart using parametric physics-informed neural networks

We present a parametric physics-informed neural network for the simulation of personalised left-ventricular biomechanics. The neural network is constrained to the biophysical problem in two ways: (i) the network output is restricted to a subspace built from radial basis functions capturing characteristic deformations of left ventricles and (ii) the cost function used for training is the energy potential functional specifically tailored for hyperelastic, anisotropic, nearly-incompressible active materials. The radial bases are generated from the results of a nonlinear Finite Element model coupled with an anatomical shape model derived from high-resolution cardiac images. We show that, by coupling the neural network with a simplified circulation model, we can efficiently generate computationally inexpensive estimations of cardiac mechanics. Our model is 30 times faster than the reference Finite Element model used, including training time, while yielding satisfactory average errors in the predictions of ejection fraction (-3%), peak systolic pressure (7%), stroke work (4%) and myocardial strains (14%). This physics-informed neural network is well suited to efficiently augment cardiac images with functional data and to generate large sets of synthetic cases for training deep network classifiers while it provides efficient personalization to the specific patient of interest with a high level of detail

Functional Polarity of Microvascular Brain Endothelial Cells Supported by Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis

The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available and standard methods so far. To circumvent these limitations, we have incorporated published data of rat brain into a robust computational model of NVU-LNAA homeostasis, allowing us to evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs across the blood brain barrier (BBB). We show that accounting for functional polarity of MBECs with either asymmetric LAT1 distribution between membranes and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is required to reproduce the experimentally measured brain ISF response to intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of these findings, we have also investigated the effect of IP administrated L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and neurons. Finally, the computational model was shown to explain the trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a competitive LAT1 inhibitor

Electro-aeromechanical modelling of actuated membrane wings

AbstractThis paper presents a numerical investigation on the aeromechanical performance of dynamically actuated membrane wings made of dielectric elastomers. They combine the advantages of membrane shape adaptability, which produces increased lift and delayed stall, with the benefits of simple, lightweight but high-authority control mechanism offered by integral actuation. High-fidelity numerical models have been developed to predict their performance and include a fluid solver based on the direct numerical integration of the unsteady Navier–Stokes equations, an electromechanical constitutive material model and a non-linear membrane structural model. Numerical results show that harmonic actuation can either increase or reduce the overall aerodynamic efficiency of the wing, measured as the mean lift-to-drag ratio, depending on the ratio between the actuation frequency and the natural frequency of the membrane. In addition, the definition of a reduced-order model based on POD modes of the complete high-fidelity system provides an insight of the main characteristics of the dynamics of the coupled system