Analysis of non-linear pulsatile blood flow in arteries

Some aspects of the problem of computation of non-linear pulsatile blood flow in large arteries are investigated, in the context of the computational method developed by Ling and Atabek (1972). As examples, the following aspects are considered: stability of the computations; representation of higher-frequency components of the flow; effects of keeping or omitting non-linear terms in the equations; effects of varying the dimensionless parameters of the problem. The computational method is extended to include effects of viscoelasticity of arterial walls.     

The influence of out-of-plane geometry on pulsatile flow within a distal end-to-side anastomosis

We present an experimental and computational investigation of time-varying flow in an idealized fully occluded 45 degrees distal end-to-side anastomosis. Two geometric configurations are assessed, one where the centerlines of host and bypass vessels lie within a plane, and one where the bypass vessel is deformed out of the plane of symmetry, respectively, termed planar and non-planar. Flow experiments were conducted by magnetic resonance imaging in rigid wall models and computations were performed using a high order spectral/hp algorithm. Results indicate a significant change in the spatial distribution of wall shear stress and a reduction of the time-averaged peak wall shear stress magnitude by 10% in the non-planar model as compared to the planar configuration. In the planar geometry the stagnation point follows a straight-line path along the host artery bed with a path length of 0.8 diameters. By contrast in the non-planar case the stagnation point oscillates about a center that is located off the symmetry plane intersection with the host artery bed wall, and follows a parabolic path with a 0.7 diameter longitudinal and 0.5 diameter transverse excursion. A definition of the oscillatory shear index (OSI) is introduced that varies between 0 and 0.5 and that accounts for a continuous range of wall shear stress vector angles. In both models, regions of elevated oscillatory shear were spatially associated with regions of separated or oscillating stagnation point flow. The mean oscillatory shear magnitude (considering sites where OSI>0.1) in the non-planar geometry was reduced by 22% as compared to the planar configuration. These changes in the dynamic behavior of the stagnation point and the oscillatory shear distribution introduced by out-of-plane graft curvature may influence the localization of vessel wall sites exposed to physiologically unfavorable flow conditions.     

Numerical simulations of pulsatile blood flow using a new constitutive model

In the present paper we use a new constitutive equation for whole human blood [R.G. Owens, A new microstructure-based constitutive model for human blood, J. Non-Newtonian Fluid Mech. (2006), to appear] to investigate the steady, oscillatory and pulsatile flow of blood in a straight, rigid walled tube at modest Womersley numbers. Comparisons are made with the experimental results of Thurston [Elastic effects in pulsatile blood flow, Microvasc. Res. 9 (1975), 145-157] for the pressure drop per unit length against volume flow rate and oscillatory flow rate amplitude. Agreement in all cases is very good. In the presentation of the numerical and experimental results we discuss the microstructural changes in the blood that account for its rheological behaviour in this simple class of flows. In this context, the concept of an apparent complex viscosity proves to be useful.     

Smoothing noisy data using dynamic programming and generalized cross-validation

Smoothing and differentiation of noisy data using spline functions requires the selection of an unknown smoothing parameter. The method of generalized cross-validation provides an excellent estimate of the smoothing parameter from the data itself even when the amount of noise associated with the data is unknown. In the present model only a single smoothing parameter must be obtained, but in a more general context the number may be larger. In an earlier work, smoothing of the data was accomplished by solving a minimization problem using the technique of dynamic programming. This paper shows how the computations required by generalized cross-validation can be performed as a simple extension of the dynamic programming formulas. The results of numerical experiments are also included.     

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.     

Gas transport during oscillatory flow in a network of branching tubes

A transport coefficient was measured for a range of oscillatory flow conditions in a branching network of tubes. Measurements were made both across the first generation of a three-generation network and the second generation of a four-generation network. The results for these two series of tests were similar, indicating that there was no significant effect due to the system boundaries. The results are cast in terms of an effective axial diffusion coefficient of the form (Formula: see text) where kappa is the molecular diffusivity, Vt is the local stroke volume (cc); and f is the oscillation frequency (Hz). These results are compared to those obtained by other investigators in branching systems of similar geometry. At low frequency, this result is found to be in approximate agreement with the steady flow result of Scherer, et al. [15]. This expression differs from the oscillatory flow results of Tarbell, et al. [19] for liquids, primarily in terms of the effects of oscillation frequency.     

Sequencing of parts and robot moves in a robotic cell

In this paper, we deal with the problem of sequencing parts and robot moves in a robotic cell where the robot is used to feed machines in the cell. The robotic cell, which produces a set of parts of the same or different types, is a flow-line manufacturing system. Our objective is to maximize the long-run average throughput of the system subject to the constraint that the parts are to be produced in proportion of their demand. The cycle time formulas are developed and analyzed for this purpose for cells producing a single part type using two or three machines. A state space approach is used to address the problem. Both necessary and sufficient conditions are obtained for various cycles to be optimal. Finally, in the case of many part types, the problem of scheduling parts for a specific sequence of robot moves in a two machine cell is formulated as a solvable case of the traveling salesman problem.     

Unidirectional and oscillatory shear stress differentially modulate NOS III gene expression.

Atherosclerotic plaques preferentially develop in regions exposed to a low mean shear stress and cyclic reversal of flow direction (oscillatory flow). This contrasts with plaque-free zones where endothelial cells are exposed to unidirectional flow. Previous works from our laboratory using a unique experimental flow system demonstrated the existence of a differential regulation of endothelial nitric oxide synthase (NOS III) gene expression by unidirectional and oscillatory flow patterns. We further studied the possible mechanisms responsible for selective unresponsiveness of NOS III gene regulation to oscillatory flow. The results obtained demonstrate that (i) induction of the activity of the 1600-base-pair NOS III gene promoter by unidirectional and oscillatory shear stress is modulated by similar mechanisms that involve NF-kappaB activation, but do not involve Ras-dependent MAP kinase activation, and (ii) the lack of induction of NOS III gene regulation by oscillatory shear stress can be attributed to the activation of a yet unidentified negative cis-acting element present in the NOS III gene.     

Flow Loading Induces Oscillatory Trajectories in a Bloodstream Parasite

The dynamics of isolated microswimmers are studied in bounded flow using the African trypanosome, a unicellular parasite, as the model organism. With the help of a microfluidics platform, cells are subjected to flow and found to follow an oscillatory path that is well fit by a sine wave. The frequency and amplitudes of the oscillatory trajectories are dependent on the flow velocity and cell orientation. When traveling in such a manner, trypanosomes orient upstream while downstream-facing cells tumble within the same streamline. A comparison with immotile trypanosomes demonstrates that self-propulsion is essential to the trajectories of trypanosomes even at flow velocities up to ～40 times higher than their own swimming speed. These studies reveal important swimming dynamics that may be generally pertinent to the transport of microswimmers in flow and may be relevant to microbial pathogenesis.     

Evaluation of Coupled Perturbed and Density Functional Methods of Computing the Parity-Violating Energy Difference between Enantiomers

We present new coupled-perturbed Hartree-Fock (CPHF) and density functional theory (DFT) computations of the parity-violating energy difference (PVED) between enantiomers for H₂O₂ and H₂S₂. Our DFT PVED computations are the first for H₂S₂ and the first with the new HCTH and OLYP functionals. Like other “second generation” PVED computations, our results are an order of magnitude larger than the original “first generation” uncoupled-perturbed Hartree-Fock computations of Mason and Tranter. We offer an explanation for the dramatically larger size in terms of cancellation of contributions of opposing signs, which also explains the basis set sensitivity of the PVED, and its conformational hypersensitivity (addressed in the following paper). This paper also serves as a review of the different types of “second generation” PVED computations: we set our work in context, comparing our results with those of four other groups, and noting the good agreement between results obtained by very different methods. DFT PVEDs tend to be somewhat inflated compared to the CPHF values, but this is not a problem when only sign and order of magnitude are required. Our results with the new OLYP functional are less inflated than those with other functionals, and OLYP is also more efficient computationally. We therefore conclude that DFT computation offers a promising approach for low-cost extension to larger biosystems, especially polymers. The following two papers extend to terrestrial and extra-terrestrial amino acids respectively, and later work will extend to polymers.     

Shape optimization in unsteady blood flow: a numerical study of non-Newtonian effects

This paper presents a numerical study of non-Newtonian effects on the solution of shape optimization problems involving unsteady pulsatile blood flow. We consider an idealized two dimensional arterial graft geometry. Our computations are based on the Navier-Stokes equations generalized to non-Newtonian fluid, with the modified Cross model employed to account for the shear-thinning behavior of blood. Using a gradient-based optimization algorithm, we compare the optimal shapes obtained using both the Newtonian and generalized Newtonian constitutive equations. Depending on the shear rate prevalent in the domain, substantial differences in the flow as well as in the computed optimal shape are observed when the Newtonian constitutive equation is replaced by the modified Cross model. By varying a geometric parameter in our test case, we investigate the influence of the shear rate on the solution.     

Water Vapour Diffusion in the Substomatal Cavity

In this paper stomatal pore and substomatal cavity are considered to be elliptic cylinders, A three-dimensional diffusion model is presented, which describes the diffusion of vapour from the surfaces of the cells surrounding the cavity to the outer end of the pore Equations describing vapour diffusion in the model are set up, based on Fick's law and the law of conservation of mass, and are solved by using computer. Quantitative relation between the cavity resistance to water vapour diffusion and: stomatal aperture is obtained and is given more general theoretical explanation. Comparing the formula obtained in this paper with those of Brown and Escombe and of Cooke et al., it is found that the cavity resistance calculated by the latter two formulas are 0.5 to 1 times higher in a large rankle of stomatal aperture values. Besides, it is shown by calculating that the rates of loss from guard cells and subsidiary ceils account for 88%– 93% and 7%–12% respectively of that from epidermic cells, and the litter amounts to 86%–96% of that from all the cells in the cavity in the large range of stomatal change.     

Flow in a two-dimensional collapsible channel with rigid inlet and outlet

This paper examines mainly oscillatory behavior of a fluid-conveying collapsible tube using a two-dimensional flexible channel made of a pair of membranes. The equation of equilibrium of the membrane in a large deflection theory is coupled with the equations of continuity and momentum of an incompressible flow in a one-dimensional flow theory accounting for flow separation. An explicit finite difference method was used to solve the governing equations numerically. According to numerical results, the fluids in the inlet and outlet rigid channels have strong effects on the oscillation of the system. Depending on initial values for the numerical integration, there may exist both a stable static equilibrium and an oscillatory solution for the same parameter values, but only if the external pressure is sufficiently large.     

Analysis of Slow (Theta) Oscillations as a Potential Temporal Reference Frame for Information Coding in Sensory Cortices

While sensory neurons carry behaviorally relevant information in responses that often extend over hundreds of milliseconds, the key units of neural information likely consist of much shorter and temporally precise spike patterns. The mechanisms and temporal reference frames by which sensory networks partition responses into these shorter units of information remain unknown. One hypothesis holds that slow oscillations provide a network-intrinsic reference to temporally partitioned spike trains without exploiting the millisecond-precise alignment of spikes to sensory stimuli. We tested this hypothesis on neural responses recorded in visual and auditory cortices of macaque monkeys in response to natural stimuli. Comparing different schemes for response partitioning revealed that theta band oscillations provide a temporal reference that permits extracting significantly more information than can be obtained from spike counts, and sometimes almost as much information as obtained by partitioning spike trains using precisely stimulus-locked time bins. We further tested the robustness of these partitioning schemes to temporal uncertainty in the decoding process and to noise in the sensory input. This revealed that partitioning using an oscillatory reference provides greater robustness than partitioning using precisely stimulus-locked time bins. Overall, these results provide a computational proof of concept for the hypothesis that slow rhythmic network activity may serve as internal reference frame for information coding in sensory cortices and they foster the notion that slow oscillations serve as key elements for the computations underlying perception.     

Cluster associative memory formation in a three-layer network of phase oscillators

A three-layer network model of oscillatory associative memory is proposed. The network is capable of storing binary images, which can be retrieved upon presenting an appropriate stimulus. Binary images are encoded in the form of the spatial distribution of oscillatory phase clusters in-phase and anti-phase relative to a reference periodic signal. The information is loaded into the network using a set of interlayer connection weights. A condition for error-free pattern retrieval is formulated, delimiting the maximal number of patterns to be stored in the memory (storage capacity). It is shown that the capacity can be significantly increased by generating an optimal alphabet (basis pattern set). The number of stored patterns can reach values of the network size (the number of oscillators in each layer), which is significantly higher than the capacity of conventional oscillatory memory models. The dynamical and information characteristics of the retrieval process based on the optimal alphabet, including the size of “attraction basins“ and the input pattern distortion admissible for error-free retrieval, are investigated.     

High density respiratory syndrome: II. The mechanics of forced respiration with artificial resistive load under normobaric pressure]

The dynamics of forced inhale (I series) and exhale (II series) parameters with additional external artificial resistive load was studied under normobaric conditions. The artificial resistance to breathing increased stepwise using removable diaphragms with sequential decrease of hole diameter from 25, 17, 13, 9, 7.5, 4.5 to 3 mm. While studying forced inhale the diaphragms were set up at Fleish pipe airflow input. In the case of forced inhale the diaphragms were set up at the pipe output. A phenomenon is revealed which consists in appearance of respiratory flow oscillations on the "flow-volume" curves during forced breathing with an increase of resistive load. Frequency maxima of the oscillations were located within the range of 6-15 Hz. The possible mechanisms for appearance of respiratory muscle tremor and respiratory flow oscillations are under discussion.     

Oscillatory flow of blood in a stenosed artery

In order to understand the abnormal flow conditions of blood in a locally constricted blood vessel, the analytical results are obtained for the oscillatory flow of blood which behaves as a Newtonian fluid. It is here assumed that the surface roughness is cosine-shaped and the maximum height of the roughness is very small compared with the radius of the unconstricted tube. Numerical solutions are presented for the instantaneous flow rate, resistive impedance, wall shear stress and phase lag.     

A numerical study on hemodynamics in the left coronary bifurcation with normal and hypertension conditions

In this study, a three-dimensional analysis of the non-Newtonian blood flow was carried out in the left coronary bifurcation. The Casson model and hyperelastic and rigid models were used as the constitutive equation for blood flow and vessel wall model, respectively. Physiological conditions were considered first normal and then compliant with hypertension disease with the aim of evaluating hemodynamic parameters and a better understanding of the onset and progression of atherosclerosis plaques in the coronary artery bifurcation. Two-way fluid–structure interaction method applying a fully implicit second-order backward Euler differencing scheme has been used which is performed in the commercial code ANSYS and ANSYS CFX (version 15.0). When artery deformations and blood pressure are associated, arbitrary Lagrangian–Eulerian formulation is employed to calculate the artery domain response using the temporal blood response. As a result of bifurcation, noticeable velocity reduction and backflow formation decrease shear stress and made it oscillatory at the starting point of the LCx branch which caused the shear stress to be less than 1 and 2 Pa in the LCx and the LAD branches, respectively. Oscillatory shear index (OSI) as a hemodynamic parameter represents the increase in residence time and oscillatory wall shear stress. Because of using the ideal 3D geometry and realistic physiological conditions, the values obtained for shear stress are more accurate than the previous studies. Comparing the results of this study with previous clinical investigations shows that the regions with low wall shear stress less than 1.20 Pa and with high OSI value more than 0.3 are in more potential risk to the atherosclerosis plaque development, especially in the posterior after the bifurcation.     

A theory of blood flow in skeletal muscle

A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid-Sch?nbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations.