Annular flow of viscoelastic fluids: Analytical and numerical solutions

This work provides analytical and numerical solutions for the linear, quadratic and exponential Phan–Thien–Tanner (PTT) viscoelastic models, for axial and helical annular fully-developed flows under no slip and slip boundary conditions, the latter given by the linear and nonlinear Navier slip laws. The rheology of the three PTT model functions is discussed together with the influence of the slip velocity upon the flow velocity and stress fields. For the linear PTT model, full analytical solutions for the inverse problem (unknown velocity) are devised for the linear Navier slip law and two different slip exponents. For the linear PTT model with other values of the slip exponent and for the quadratic PTT model, the polynomial equation for the radial location (β) of the null shear stress must be solved numerically. For both models, the solution of the direct problem is given by an iterative procedure involving three nonlinear equations, one for β, other for the pressure gradient and another for the torque per unit length. For the exponential PTT model we devise a numerical procedure that can easily compute the numerical solution of the pure axial flow problem

High strain rate constitutive modeling forhistorical structures subjected to blast loading

Doctoral Thesis Civil Engineering

Dispersion of fillers in viscoelastic polymer matrices using Eulerian-Lagrangian approaches

Understanding the behavior of c omplex composite materials using mixing procedures is fundamental in several industrial processes. For instance, polymer composites are usually manufactured using dispersion of fillers in polymer melt matrices. The success of the filler dispersion depends both on the complex flow patterns generated and on the polymer melt rheological behavior. Consequently, the availability of a numerical tool that allow to model both fluid and particle would be very useful to increase the process insight. Nowadays there ar e computational tools that allow modeling the behavior of filled systems, taking into account both the behavior of the fluid (Computational Rheology) and the particles (Discrete Element Method). One example is the DPMFoam solver of the OpenFOAM ® framework where the averaged volume fraction momentum and mass conservation equations are used to describe the fluid (continuous phase) rheology, and the Newton’s second law of motion is used to compute the particles (discrete phase) movement. In this work the refer red solver is extended to take into account the elasticity of the polymer melts for the continuous phase. The solver capabilities will be illustrated by studying the effect of the fluid rheology on the filler dispersion, taking into account different fluid types (generalized Newtonian or viscoelastic) and particles volume fraction and size. The results obtained are used to evaluate the relevance of considering the fluid complex rheology for the prediction of the composites morphology

Influence of the hip joint modeling approaches on the kinematics of human gait

The influence of the hip joint formulation on the kinematic response of the model of human gait is investigated throughout this work. To accomplish this goal, the fundamental issues of the modeling process of a planar hip joint under the framework of multibody systems are revisited. In particular, the formulations for the ideal, dry, and lubricated revolute joints are described and utilized for the interaction of femur head inside acetabulum or the hip bone. In this process, the main kinematic and dynamic aspects of hip joints are analyzed. In a simple manner, the forces that are generated during human gait, for both dry and lubricated hip joint models, are computed in terms of the system’s state variables and subsequently introduced into the dynamics equations of motion of the multibody system as external generalized forces. Moreover, a human multibody model is considered, which incorporates the different approaches for the hip articulation, namely ideal joint, dry, and lubricated models. Finally, several computational simulations based on different approaches are performed, and the main results presented and compared to identify differences among the methodologies and procedures adopted in this work. The input conditions to the models correspond to the experimental data capture from an adult male during normal gait. In general, the obtained results in terms of positions do not differ significantly when the different hip joint models are considered. In sharp contrast, the velocity and acceleration plotted vary significantly. The effect of the hip joint modeling approach is clearly measurable and visible in terms of peaks and oscillations of the velocities and accelerations. In general, with the dry hip model, intra-joint force peaks can be observed, which can be associated with the multiple impacts between the femur head and the cup. In turn, when the lubricant is present, the system’s response tends to be smoother due to the damping effects of the synovial fluid.

Modelação, simulação e implementação de agitação acústica para aplicações em microfluídica

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Optimized venous return with a self-expanding cannula: from computational fluid dynamics to clinical application.

The Smart canula concept allows for collapsed cannula insertion, and self-expansion within a vein of the body. (A) Computational fluid dynamics, and (B) bovine experiments (76+/-3.8 kg) were performed for comparative analyses, prior to (C) the first clinical application. For an 18F access, a given flow of 4 l/min (A) resulted in a pressure drop of 49 mmHg for smart cannula versus 140 mmHg for control. The corresponding Reynolds numbers are 680 versus 1170, respectively. (B) For an access of 28F, the maximal flow for smart cannula was 5.8+/-0.5 l/min versus 4.0+/-0.1 l/min for standard (P<0.0001), for 24F 5.5+/-0.6 l/min versus 3.2+/-0.4 l/min (P<0.0001), and for 20F 4.1+/-0.3 l/min versus 1.6+/-0.3 l/min (P<0.0001). The flow obtained with the smart cannula was 270+/-45% (20F), 172+/-26% (24F), and 134+/-13% (28F) of standard (one-way ANOVA, P=0.014). (C) First clinical application (1.42 m2) with a smart cannula showed 3.55 l/min (100% predicted) without additional fluids. All three assessment steps confirm the superior performance of the smart cannula design.

Modeling Dependence Structure and Forecasting Portfolio Value-at-Risk with Dynamic Copulas

We study the asymmetric and dynamic dependence between financial assets and demonstrate, from the perspective of risk management, the economic significance of dynamic copula models. First, we construct stock and currency portfolios sorted on different characteristics (ex ante beta, coskewness, cokurtosis and order flows), and find substantial evidence of dynamic evolution between the high beta (respectively, coskewness, cokurtosis and order flow) portfolios and the low beta (coskewness, cokurtosis and order flow) portfolios. Second, using three different dependence measures, we show the presence of asymmetric dependence between these characteristic-sorted portfolios. Third, we use a dynamic copula framework based on Creal et al. (2013) and Patton (2012) to forecast the portfolio Value-at-Risk of long-short (high minus low) equity and FX portfolios. We use several widely used univariate and multivariate VaR models for the purpose of comparison. Backtesting our methodology, we find that the asymmetric dynamic copula models provide more accurate forecasts, in general, and, in particular, perform much better during the recent financial crises, indicating the economic significance of incorporating dynamic and asymmetric dependence in risk management.

The borehole-fluid effect in electrical resistivity imaging

Fluid that fills boreholes in crosswell electrical resistivity investigations provides the necessary electrical contact between the electrodes and the rock formation but it is also the source of image artifacts in standard inversions that do not account for the effects of the boreholes. The image distortions can be severe for large resistivity contrasts between the rock formation and borehole fluid and for large borehole diameters. We have carried out 3D finite-element modeling using an unstructured-grid approach to quantify the magnitude of borehole effects for different resistivity contrasts, borehole diameters, and electrode configurations. Relatively common resistivity contrasts of 100:1 and borehole diameters of 10 and 20 cm yielded, for a bipole length of 5 m, apparent resistivity underestimates of approximately 12% and 32% when using AB-MN configurations and apparent resistivity overestimates of approximately 24% and 95% when using AM-BN configurations. Effects are generally more severe at shorter bipole spacings. We report the results obtained by either including or ignoring the boreholes in inversions of 3D field data from a test site in Switzerland, where approximately 10,000 crosswell resistivity-tomography measurements were made across six acquisition planes among four boreholes. Inversions of raw data that ignored the boreholes filled with low-resistivity fluid paradoxically produced high-resistivity artifacts around the boreholes. Including correction factors based on the modeling results fora ID model with and without the boreholes did not markedly improve the images. The only satisfactory approach was to use a 3D inversion code that explicitly incorporated the boreholes in the actual inversion. This new approach yielded an electrical resistivity image that was devoid of artifacts around the boreholes and that correlated well with coincident crosswell radar images.

Hybrid Multiscale Finite Volume method for two-phase flow in porous media

We present a novel hybrid (or multiphysics) algorithm, which couples pore-scale and Darcy descriptions of two-phase flow in porous media. The flow at the pore-scale is described by the Navier?Stokes equations, and the Volume of Fluid (VOF) method is used to model the evolution of the fluid?fluid interface. An extension of the Multiscale Finite Volume (MsFV) method is employed to construct the Darcy-scale problem. First, a set of local interpolators for pressure and velocity is constructed by solving the Navier?Stokes equations; then, a coarse mass-conservation problem is constructed by averaging the pore-scale velocity over the cells of a coarse grid, which act as control volumes; finally, a conservative pore-scale velocity field is reconstructed and used to advect the fluid?fluid interface. The method relies on the localization assumptions used to compute the interpolators (which are quite straightforward extensions of the standard MsFV) and on the postulate that the coarse-scale fluxes are proportional to the coarse-pressure differences. By numerical simulations of two-phase problems, we demonstrate that these assumptions provide hybrid solutions that are in good agreement with reference pore-scale solutions and are able to model the transition from stable to unstable flow regimes. Our hybrid method can naturally take advantage of several adaptive strategies and allows considering pore-scale fluxes only in some regions, while Darcy fluxes are used in the rest of the domain. Moreover, since the method relies on the assumption that the relationship between coarse-scale fluxes and pressure differences is local, it can be used as a numerical tool to investigate the limits of validity of Darcy's law and to understand the link between pore-scale quantities and their corresponding Darcy-scale variables.

A flow cytometry based oligotrophic pollutant exposure test to detect bacterial growth inhibition and cell injury.

Toxicity of chemical pollutants in aquatic environments is often addressed by assays that inquire reproductive inhibition of test microorganisms, such as algae or bacteria. Those tests, however, assess growth of populations as a whole via macroscopic methods such as culture turbidity or colony-forming units. Here we use flow cytometry to interrogate the fate of individual cells in low-density populations of the bacterium Pseudomonas fluorescens SV3 exposed or not under oligotrophic conditions to a number of common pollutants, some of which derive from oil contamination. Cells were stained at regular time intervals during the exposure assay with fluorescent dyes that detect membrane injury (i.e., live-dead assay). Reduction of population growth rates was observed upon toxicant insult and depended on the type of toxicant. Modeling and cell staining indicate that population growth rate decrease is a combined effect of an increased number of injured cells that may or may not multiply, and live cells dividing at normal growth rates. The oligotrophic assay concept presented here could be a useful complement for existing biomarker assays in compliance with new regulations on chemical effect studies or, more specifically, for judging recovery after exposure to fluctuating toxicant conditions.

Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients

INTRODUCTION Although several parameters have been proposed to predict the hemodynamic response to fluid expansion in critically ill patients, most of them are invasive or require the use of special monitoring devices. The aim of this study is to determine whether noninvasive evaluation of respiratory variation of brachial artery peak velocity flow measured using Doppler ultrasound could predict fluid responsiveness in mechanically ventilated patients. METHODS We conducted a prospective clinical research in a 17-bed multidisciplinary ICU and included 38 mechanically ventilated patients for whom fluid administration was planned due to the presence of acute circulatory failure. Volume expansion (VE) was performed with 500 mL of a synthetic colloid. Patients were classified as responders if stroke volume index (SVi) increased >or= 15% after VE. The respiratory variation in Vpeakbrach (DeltaVpeakbrach) was calculated as the difference between maximum and minimum values of Vpeakbrach over a single respiratory cycle, divided by the mean of the two values and expressed as a percentage. Radial arterial pressure variation (DeltaPPrad) and stroke volume variation measured using the FloTrac/Vigileo system (DeltaSVVigileo), were also calculated. RESULTS VE increased SVi by >or= 15% in 19 patients (responders). At baseline, DeltaVpeakbrach, DeltaPPrad and DeltaSVVigileo were significantly higher in responder than nonresponder patients [14 vs 8%; 18 vs. 5%; 13 vs 8%; P < 0.0001, respectively). A DeltaVpeakbrach value >10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%. A DeltaPPrad value >10% and a DeltaSVVigileo >11% predicted volume responsiveness with a sensitivity of 95% and 79%, and a specificity of 95% and 89%, respectively. CONCLUSIONS Respiratory variations in brachial artery peak velocity could be a feasible tool for the noninvasive assessment of fluid responsiveness in patients with mechanical ventilatory support and acute circulatory failure. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT00890071.

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients

RESUME : Objectif: Le glioblastome multiforme (GBM) est la tumeur cérébrale maligne la plus agressive qui conduit au décès de la majorité des patients moins d'une année après le diagnostic. La plupart des agents chimiothérapeutiques actuellement disponibles ne traversent pas la barrière hémato¬encéphalique et ne peuvent par conséquent pas être utilisés pour ce type de tumeur. Le Temozolomide (TMZ) est un nouvel agent alkylant récemment développé pour le traitement des gliomes malins. A ce jour, très peu d'informations sont disponibles sur la pénétration intra-cérébrale de cet agent. Au cours d'une étude pilote de phase II menée auprès de 64 patients atteints de GBM, l'administration précoce de TMZ combinée à une radiothérapie standard (RT) afin d'intervenir au plus tôt dans l'évolution de la maladie, a permis de prolonger la survie de ces patients, résultat qui pu être confirmé par la suite lors de l'étude randomisée de phase III. L'objectif de cette étude a été de déterminer les paramètres pharmacocinétique du TMZ dans le plasma et le liquide céphalo-rachidien (LCR), d'évaluer l'influence de certains facteurs individuels (âge, sexe, surface corporelle, fonction rénale/hépatique, co-médications, RT concomitante) sur ces différents paramètres, et enfin d'explorer la relation existant entre l'exposition au TMZ et certains marqueurs cliniques d'efficacité et de toxicité. Matériel et Méthode: Les concentrations de TMZ ont été mesurées par chromatographie liquide à haute performance (HPLC) dans le plasma et le LCR de 35 patients atteints de GBM nouvellement diagnostiqués (étude pilote) ou de gliomes malins en récidive (étude récidive). L'analyse pharmacocinétique de population a été réalisée à l'aide du programme NONMEM. L'exposition systémique et cérébrale, définie par les AUC (Area Under the time-concentration Curve) dans le plasma et le LCR, a été estimée pour chaque patient et corrélée à la toxicité, la survie ainsi que la survie sans progression tumorale. Résultats: Un modèle à 1 compartiment avec une cinétique d'absorption et de transfert Kplasma -> LCR de ordre a été retenu afin de décrire le profil pharmacocinétique du TMZ. Les valeurs moyennes de population ont été de 10 L/h pour la clairance, de 30.3 L pour le volume de distribution, de 2.1 h pour la 1/2 vie d'élimination, de 5.78 hE-1 pour la constante d'absorption, de 7.2 10E4 hE-1 pour Kplasma->LCR et de 0.76 hE-1 pour KLCR plasma. La surface corporelle a montré une influence significative sur la clairance et le volume de distribution, alors que le sexe influence la clairance uniquement. L'AUC mesurée dans le LCR représente ~20% de celle du plasma et une augmentation de 15% de Kplasma->LCR a été observée lors du traitement concomitant de radiochimiothérapie. Conclusions: Cette étude est la première analyse pharmacocinétique effectuée chez l'homme permettant de quantifier la pénétration intra-cérébrale du TMZ. Le rapport AUC LCR/AUC Plasma a été de 20%. Le degré d'exposition systémique et cérébral au TMZ ne semble pas être un meilleur facteur prédictif de la survie ou de la tolérance au produit que ne l'est la dose cumulée seule. ABSTRACT Purpose: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of ma¬lignant brain tumors. The purpose was to assess TNIZ phar¬macokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covari¬ates and to explore relationships between systemic or cere¬bral drug exposure and clinical outcomes. Experimental Design: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacoki¬netic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area un¬der the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival. Results: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (VD), 30.3 liters; absorption constant rate, 5.8 hE-1; elimination half-time, 2.1 h; transfer rate from plasma to CSF (Kplasma->CSF), 7.2 x 10E-4hE-1 and the backwards rate, 0.76hE-1. Body surface area signifi¬cantly influenced both clearance and VD, and clearance was sex dependent. The AU CSF corresponded to 20% of the AUCplasma. A trend toward an increased K plasma->CSF of 15% was observed in case of concomitant radiochemo-therapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. Conclusions: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC CSF/ AUC plasma ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Vasopressin-dependent coupling between sodium transport and water flow in a mouse cortical collecting duct cell line.

Water balance is achieved through the ability of the kidney to control water reabsorption in the connecting tubule and the collecting duct. In a mouse cortical collecting duct cell line (mCCD(c11)), physiological concentrations of arginine vasopressin increased both electrogenic, amiloride-sensitive, epithelial sodium channel (ENaC)-mediated sodium transport measured by the short-circuit current (Isc) method and water flow (Jv apical to basal) measured by gravimetry with similar activation coefficient K(1/2) (6 and 12 pM, respectively). Jv increased linearly according to the osmotic gradient across the monolayer. A small but highly significant Jv was also measured under isoosmotic conditions. To test the coupling between sodium reabsorption and water flow, mCCD(c11) cells were treated for 24 h under isoosmotic condition with either diluent, amiloride, vasopressin or vasopressin and amiloride. Isc, Jv, and net chemical sodium fluxes were measured across the same monolayers. Around 30% of baseline and 50% of vasopressin-induced water flow is coupled to an amiloride-sensitive, ENaC-mediated, electrogenic sodium transport, whereas the remaining flow is coupled to an amiloride-insensitive, nonelectrogenic sodium transport mediated by an unknown electroneutral transporter. The mCCD(c11) cell line is a first example of a mammalian tight epithelium allowing quantitative study of the coupling between sodium and water transport. Our data are consistent with the 'near isoosmotic' fluid transport model.