Dynamics of blood flow: modeling of Fåhraeus and Fåhraeus–Lindqvist effects using a shear-induced red blood cell migration model

Blood flow in micro capillaries of diameter approximately 15–500 μm is accompanied with a lower tube hematocrit level and lower apparent viscosity as the diameter decreases. These effects are termed the Fåhraeus and Fåhraeus–Lindqvist effects, respectively. Both effects are linked to axial accumulation of red blood cells. In the present investigation, we extend previous works using a shear-induced model for the migration of red blood cells and adopt a model for blood viscosity that accounts for the suspending medium viscosity and local hematocrit level. For fully developed hematocrit profiles (i.e., independent of axial location), the diffusion fluxes due to particle collision frequency and viscosity gradients are of equal magnitude and opposite directions. The ratio of the diffusion coefficients for the two fluxes affects both the Fåhraeus and Fåhraeus–Lindqvist effects and is found related to the capillary diameter and discharge hematocrit using a well-known data-fit correlation for apparent blood viscosity. The velocity and hematocrit profiles were determined numerically as functions of radial coordinate, tube diameter, and discharge hematocrit. The velocity profile determined numerically is consistent with the derived analytical expression and the results are in good agreement with published numerical results and experimental data for hematocrit ratio and hematocrit and velocity profiles.     

Validation of a fluid–structure interaction numerical model for predicting flow transients in arteries

Fluid–structure interaction (FSI) numerical models are now widely used in predicting blood flow transients. This is because of the importance of the interaction between the flowing blood and the deforming arterial wall to blood flow behaviour. Unfortunately, most of these FSI models lack rigorous validation and, thus, cannot guarantee the accuracy of their predictions. This paper presents the comprehensive validation of a two-way coupled FSI numerical model, developed to predict flow transients in compliant conduits such as arteries. The model is validated using analytical solutions and experiments conducted on polyurethane mock artery. Flow parameters such as pressure and axial stress (and precursor) wave speeds, wall deformations and oscillating frequency, fluid velocity and Poisson coupling effects, were used as the basis of this validation. Results show very good comparison between numerical predictions, analytical solutions and experimental data. The agreement between the three approaches is generally over 95%. The model also shows accurate prediction of Poisson coupling effects in unsteady flows through flexible pipes, which up to this stage have only being predicted analytically. Therefore, this numerical model can accurately predict flow transients in compliant vessels such as arteries.     

Use of β-galactosidase liposome model as a novel method to screen freeze-drying cryoprotectants

This study developed a novel method of screening cryoprotectants used to improve the survivability of lyophilized Lactobacillus helveticus. To develop a liposome encapsulated β-galactosidase (β-gal) as a cell membrane model, the β-gal liposome was characterized in terms of mean size, poly dispersity index, zeta potential, along with transmission electron microscopy. 800 W of ultrasonic power and 10 min of sonication time were the optimal experimental conditions to obtain the desirable β-gal liposome. Subsequently, different cryoprotectants were mixed with the β-gal liposome during freeze-drying. After freeze-drying, liposomes were hydrolized, and the protective effect of cryoprotectants was assessed as the release rate of encapsulated β-gal. The lowest release rate of β-gal was obtained using 10 mg/100 ml trehalose and 0.2 mg/100 ml hyaluronic acid.     

Heat transfer analysis of peristaltic flow of a Phan-Thien–Tanner fluid model due to metachronal wave of cilia

Biomechanics and Modeling in Mechanobiology - In the present investigation, we have studied the effects of heat transfer on the peristaltic flow considering the Phan-Thien–Tanner fluid model....     

The use of bioreactor kinetics to quantify the effects of interfering agents on bioreactor efficiency: ‘Proof of principle’ using uranium-accumulating Citrobacter sp. in a plug flow reactor

Summary Using previously established kinetic methods a technique is described which provides a handle to assess quantitatively the interfering effect of an excess of chloride ions on uranium accumulation within an immobilized biofilm bioreactor. The use of two cell supports permits demonstration of the method in an immobilized biofilm model system.     

Does gravitational pressure of blood hinder flow to the brain of the giraffe?

Vascular pressure consists of the sum of two pressures: (a) pressure developed by the pumping of the ventricles against the resistance of vessels, designated as viscous flow pressure, and (b) pressure caused by gravity, traditionally called hydrostatic, better described as gravitational pressure. In a conduit, both of these pressures must be overcome when a liquid is discharged to a higher level of gravitational potential energy. If a liquid is returned to its original level, gravity neither helps nor hinders flow because of the siphon effect. This circumstance prevails in the circulatory system. Hence, P1-P2 in the Poiseuille equation excludes gravitational pressure between those points. The long neck of the giraffe, therefore, poses no impediment to blood flow in the erect posture. The giraffe has a high aortic pressure. This is not for driving the blood to its head but is for minimizing the gravitational drop of intravascular pressure and collapse of the vessels. The cerebral circulation is protected by the cerebrospinal fluid which undergoes parallel changes in pressure with posture. Other vessels in the head are less protected by connective tissue, surrounding muscles and other structures. The high aortic pressure in the giraffe is probably caused by the high total peripheral resistance of the systemic circuit due to vascular adaptations related to the overall height of the animal.     

Ca²⁺ sensitization of cardiac myofilament proteins contributes to exercise training-enhanced myocardial function in a porcine model of chronic occlusion

Exercise training has been shown to improve cardiac dysfunction in both patients and animal models of coronary artery disease; however, the underlying cellular and molecular mechanisms have not been completely understood. We hypothesized that exercise training would improve force generation in the myocardium distal to chronic coronary artery occlusion via altered intracellular Ca(2+) concentration ([Ca(2+)](i)) cycling and/or Ca(2+) sensitization of myofilaments. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of adult female Yucatan pigs. Twenty-two weeks postoperatively, the myocardium was isolated from nonoccluded (left anterior descending artery dependent) and collateral-dependent (formerly left circumflex coronary artery dependent) regions of sedentary (pen confined) and exercise-trained (treadmill run, 5 days/wk for 14 wk) pigs. Force measurements in myocardial strips showed that the percent change in force at stimulation frequencies of 3 and 4 Hz relative to 1 Hz was significantly higher in exercise-trained pigs compared with sedentary pigs. β-Adrenergic stimulation with dobutamine significantly improved force kinetics in myocardial strips of sedentary but not exercise-trained pigs at 1 Hz. Additionally, time to peak and half-decay of intracellular Ca(2+) (340-to-380-nm fluoresence ratio) responses at 1 Hz were significantly decreased in the collateral-dependent region of exercise-trained pigs with no difference in peak [Ca(2+)](i) between groups. Furthermore, the skinned myocardium from exercise-trained pigs showed an increase in Ca(2+) sensitivity compared with sedentary pigs. Immunoblot analysis revealed that the relative levels of cardiac troponin T and β(1)-adrenergic receptors were decreased in hearts from exercise-trained pigs independent of occlusion. Also, the ratio of phosphorylated to total myosin light chain-2, basal phosphorylation levels of cardiac troponin I (Ser(23) and Ser(24)), and cardiac myosin binding protein-C (Ser(282)) were unaltered by occlusion or exercise training. Thus, our data demonstrate that exercise training-enhanced force generation in the nonoccluded and collateral-dependent myocardium was associated with improved Ca(2+) transients, increased Ca(2+) sensitization of myofilament proteins, and decreased expression levels of β(1)-adrenergic receptors and cardiac troponin T.     

Convergence of a structured metapopulation model to Levins’s model

We consider a structured metapopulation model describing the dynamics of a single species, whose members are located in separate patches that are linked through migration according to a mean field rule. Our main aim is to find conditions under which its equilibrium distribution is reasonably approximated by that of the unstructured model of Levins (1969). We do this by showing that the (positive) equilibrium distribution converges, as the carrying capacity of each population goes to infinity together with appropriate scalings on the other parameters, to a bimodal distribution, consisting of a point mass at 0, together with a positive part which is closely approximated by a shifted Poisson centred near the carrying capacity. Under this limiting régime, we also give simpler approximate formulae for the equilibrium distribution. We conclude by showing how to compute persistence regions in parameter space for the exact model, and then illustrate all our results with numerical examples. Our proofs are based on Steins method.Supported in part by Schweizer Nationalfonds Projekt Nrs 20–61753.00 and 20–67909.02Supported in part by CNR of Italy under Grant n. 00.0142.ST74     

Validation of a method for “dose of the day” calculation in head-neck tomotherapy by using planning ct-to-MVCT deformable image registration

PurposeThe aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT).MethodsFor each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2 mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D-Slicer.ResultsOn average, 87.9% ± 1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6% ± 0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8% ± 0.8% of body’s voxels.ConclusionsThis study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.     

Results of the oxygen Fick method in a closed blood circulation model including “total arteriovenous diffusive shunt of oxygen”

It is considered that arteriovenous diffusive shunts of oxygen may cause inaccuracy of the oxygen Fick method as where is the pulmonary oxygen uptake, is the cardiac output, and CaO₂ and CvO₂ are the arterial and venous oxygen contents, respectively. A simple circulation model, including the whole circulation with nine well-mixed compartments (C1, ... C9), is constructed: the is assigned as constant as 6000 ml min⁻¹; the blood portions of 60 ml move at an interval of 600 ms. C1 and C2 compartments, each having 60 ml volume, represent the blood of pulmonary microcirculation, C3 represents the arterial blood with a volume of 1500 ml, C4, ..., C8, each also having a volume of 60 ml, represent the blood of peripheral microcirculation, whereas C9 represents the venous blood with a volume of 3000 ml. The pulmonary oxygen uptake , related to C1 and C2, the oxygen release , related to C4,...,C8, as well as a “total arteriovenous diffusive shunt of oxygen” , from the arterial blood (C3) to the venous blood (C9), are calculated simultaneously. The alveolar gas has a constant oxygen partial pressure, and the pulmonary diffusion capacity is also constant; similar to modeling the pulmonry, oxygen diffusion, constant partial oxygen pressures for all peripheral tissues as well as constant diffusion capacities for all peripheral oxygen diffusion are also assigned. The diffusion capacities for the (between C3 and C9) are arbitrarily assigned. The Fick method gives incorrect results depending on the total arteriovenous diffusive shunt of oxygen . But the mechanism determining the magnitude of remains unclear.     

Validation of a prefractionation method followed by two-dimensional electrophoresis – Applied to cerebrospinal fluid proteins from frontotemporal dementia patients

Background  

The aim of this study was firstly, to improve and validate a cerebrospinal fluid (CSF) prefractionation method followed by two-dimensional electrophoresis (2-DE) and secondly, using this strategy to investigate differences between the CSF proteome of frontotemporal dementia (FTD) patients and controls. From each subject three ml of CSF was prefractionated using liquid phase isoelectric focusing prior to 2-DE.     

Using a fine root extraction device to quantify small diameter corn roots (≥0.025 mm) in field soils

The study of fine roots growing under field conditions is limited by the techniques currently available for separating these roots from soil. This study had two objectives: to measure the total root length of field grown corn (Zea mays L.) by root diameter class, and to develop an inexpensive and efficient root washing device that would effectively capture all of the roots in a field soil sample. An inexpensive Fine Root Extraction Device (FRED) was constructed from readily available materials and was successful at extracting all roots, including very fine diameter roots (0.025 mm), from field soil samples. Greater than 99.7% of marked roots introduced to the FRED were recaptured by the device. Soil samples from three depths, and on three dates, from field grown corn were placed in the FRED. We found that more than 56% of total root length occurred in roots whose diameters were smaller than 0.175 mm, and more than 35% of root length occurred in roots smaller than 0.125 mm in diameter. Corn roots of the diameters described here have not been reported in field soils prior to this study. Root researchers who fail to measure these very fine roots will significantly underestimate root length density. Widespread use of the FRED should improve our understanding of root distribution in field soils.     

A method for assessing the fit of a constitutive material model to experimental stress–strain data

Higher-order polynomial functions can be used as a constitutive model to represent the mechanical behaviour of biological materials. The goal of this study was to present a method for assessing the fit of a given constitutive three-dimensional material model. Goodness of fit was assessed using multiple parameters including the root mean square error and Hotelling's T ²-test. Specifically, a polynomial model was used to characterise the stress–strain data, varying the number of model terms used (45 combinations of between 3 and 11 terms) and the manner of optimisation used to establish model coefficients (i.e. determining coefficients either by parameterisation of all data simultaneously or averaging coefficients obtained by parameterising individual data trials). This framework for model fitting helps to ensure that a given constitutive formulation provides the best characterisation of biological material mechanics.     

Induction of specific human primary immune responses to a Semliki Forest virus–based tumor vaccine in a Trimera mouse model

Recombinant Semliki Forest virus (rSFV) enables high-level, transient expression of heterologous proteins in vivo, and is believed to be a superior vector for genetic vaccination, compared with the conventional DNA plasmid. Nonetheless, the efficacy of rSFV-based vaccine in eliciting human immune responses has not been tested. We used a Trimera mouse model, consisting of lethally irradiated BALB/c host reconstituted with nonobese diabetes/severe combined immunodeficiency (NOD/SCID) bone marrow plus human peripheral blood mononuclear cells (PBMCs), to characterize the in vivo immune responses against rSFV-encoded human melanoma antigen MAGE-3. MAGE-3–specific antibody and cytotoxic T lymphocyte (CTL) activity were detected by ELISA and ⁵¹Cr-release assay, respectively, and the responses were compared with those induced by a plasmid DNA vaccine encoding the same antigen. The results showed that rSFV vaccine could elicit human MAGE-3–specific antibody and CTL response in the Trimera mice, and the antitumor responses were more potent than those by plasmid DNA vaccination. This is the first report to evaluate human immune responses to an rSFV-based tumor vaccine in the Trimera mouse model. Our data suggest that rSFV vector is better than DNA plasmid in inducing protective immunity, and the Trimera model may serve as a general tool to evaluate the efficacy of tumor vaccines in eliciting human primary immune response in vivo.     

Development of a urinary free cortisol assay using solid-phase extraction–capillary electrophoresis

In clinical practice, the measurement of urinary free cortisol (UFC) provides the most sensitive and specific diagnostic information for excess adrenal production of cortisol. The existing methodologies (RIA and HPLC) are time consuming, costly, involve tedious extractions, derivatizations and problems with non-specific interactions with cortisol metabolites in urine. In the present study, we describe the development of an SPE–CE method for the rapid analysis of UFC. UFC was concentrated using SPE C₁₈ cartridges (3M Empore) under a vacuum and eluted with acetonitrile–SDS. The use of 10% acetone to wash cartridges before final elution with acetonitrile–SDS showed significant improvements in the free cortisol recovery. The complete extraction was accomplished in 10–15 min with a recovery of 89–94%. CE analysis was done on a Beckman P/ACE 5010 with detection at 254 nm using a neutral capillary. Detection limits of free cortisol in urine was improved to 10 μg/l with SPE compared to 500 μg/l without SPE. No interferences either from BSA or other urinary cortisol metabolites affected the free cortisol determinations. The results showed the feasibility of a rapid UFC detection with improved sample handling capacity.     

Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators

In this paper, we develop a physiological oscillator model of which the output mimics the shape of the R-R interval Poincaré plot. To validate the model, simulations of various nervous conditions are compared with heart rate variability (HRV) data obtained from subjects under each prescribed condition. For a variety of sympathovagal balances, our model generates Poincaré plots that undergo alterations strongly resembling those of actual R-R intervals. By exploiting the oscillator basis of our model, we detail the way that low- and high-frequency modulation of the sinus node translates into R-R interval Poincaré plot shape by way of simulations and analytic results. With the use of our model, we establish that the length and width of a Poincaré plot are a weighted combination of low- and high-frequency power. This provides a theoretical link between frequency-domain spectral analysis techniques and time-domain Poincaré plot analysis. We ascertain the degree to which these principles apply to real R-R intervals by testing the mathematical relationships on a set of data and establish that the principles are clearly evident in actual HRV records.     

Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

During the past several decades, many risk factors for cerebrovascular and cardiovascular disease have been identified. More recently, it has been appreciated that inadequate nutrition and/or other intrauterine factors during fetal development may play an important role in the genesis of these conditions. An additional stress factor that may "program" the fetus for disease later in life is chronic hypoxia. In studies originally designed to examine the function of developing cerebral arterial function in response to long-term hypoxia (LTH), it has become clear that many cellular and subcellular changes may have important implications for later life. Here we review some of the significant alterations in fetal cerebral artery structure and function induced by high-altitude (3,820 m, 12,470 ft) LTH ( approximately 110 days). LTH is associated with augmentation or upregulation of presynaptic functions, including responses to perivascular (i.e., sympathetic) nerve stimulation, and structural maturational changes. In contrast, many postsynaptic functions related to the Ca(2+)-dependent contractile pathway tend to be downregulated, whereas elements of the Ca(2+)-independent contraction pathway are upregulated. The results emphasize the role of high-altitude LTH in modulating many aspects of electromechanical and pharmacomechanical coupling in the developing cerebral vasculature. A complicating factor is that the regulation of cerebrovascular tone by Ca(2+)-dependent and Ca(2+)-independent pathways changes significantly as a function of maturational age. In addition to highlighting independent regulation of various elements of the signal transduction cascade, the studies demonstrate the potential for LTH to program the fetus for cerebrovascular and other disease as an adult.     

Validation of a Fluid–Structure Interaction Model of a Heart Valve using the Dynamic Mesh Method in Fluent

Simulations of coupled problems such as fluid–structure interaction (FSI) are becoming more and more important for engineering purposes. This is particularly true when modeling the aortic valve, where the FSI between the blood and the valve determines the valve movement and the valvular hemodynamics. Nevertheless only a few studies are focusing on the opening and closing behavior during the ejection phase (systole). In this paper, we present the validation of a FSI model using the dynamic mesh method of Fluent for the two-dimensional (2D) simulation of mechanical heart valves during the ejection phase of the cardiac cycle. The FSI model is successfully validated by comparing simulation results to experimental data obtained from in vitro studies using a CCD camera.