Analysis of blood flow through a model of the human arterial system under periodic body acceleration

The human system may be subjected to a body acceleration deliberated for example by making subjects lie down on vibrating tables or more frequently unintentionally, for example during travel in water and land or in air and space. The present study is concerned with the effects of externally imposed body accelerations on blood flow in a branched system of arteries. A finite-element model of flow in the arterial system subject to periodic body accelerations is presented. Computational results on the flow rates through selected arteries and the corresponding inlet and outlet pressures under different conditions (magnitude, frequency and direction) of applied acceleration are presented.     

Bioreactors for 3-dimensional high-density culture of human cells

A bioreactor was developed as an instrument to culture human or animal cells that require attachment in a large quantity or at a high density. The purpose for developing such a bioreactor is two-fold: to produce a large quantity of animal or human cells that have been modified by gene recombination technology to accommodate manufacture of physiologically-active substances or human proteins on an industrial scale; and for research to culture animal cells to form a high-density 3-dimensional structure as a morphological or functional tissue or organ entity. In the current report, the circulatory flow bioreactor and radial flow bioreactor (RFB) are introduced, in which the former can be scaled up. As a small bioreactor produced for the latter purpose, a rotary cell culture system and novel multicoaxial hollow-fiber bioreactor are introduced. Finally, a small RFB culture system that was scaled down by the present author and his collaborators for the study of a 3-dimensional high density culture system is described. The RFB can be readily scaled up for manufacturing or scaled down for research purposes. This is a cell culturing system that can induce the functions of human tissues by preparing a high density 3-dimensional organization of cells of human origin.     

Phasic flow patterns at a hemodialysis venous anastomosis

A phase-by-phase analysis of local flow patterns at the venous anastomosis of an arteriovenous hemodialysis angioaccess loop graft (AVLG) was made. The study was carried out in an elastic, transparent Silastic in vitro flow model, which duplicates the detail geometry of the AVLG obtained from an animal model (30+ kg dogs with 12 weeks bilateral femoral AVLG implantation). The flow model was installed in a mock pulsatile flow loop system designed to simulate physiological conditions. Flow visualization was made in laser-illuminated flow fields using a high-speed cine camera. Analysis of the high-speed cine indicates there is a distinct separation region downstream of the anastomotic toe in the median plane and a stagnation region that oscillates along the opposite wall. During inward motion of the vessel wall, accumulation of particles in the separation region and the nearby stagnation region is observed. A large swirl appears in the distal vein during end-systolic period. A double-helical flow pattern occurs further down in the distal vein. Retrograde flow in the distal vein occurs in an "oscillating" manner following each cardiac cycle.     

Performance of one- and two-dimensional models for a slow flow system in a long,permeable tubule

A radially symmetric slow flow system in a long cylinder with moderate wall leakage is considered, with physical parameters taken from the renal proximal tubule. Dimensional analysis yields a simplified system which, under certain assumptions, is well-posed, and possesses a unique solution if a solution exists. A lumped parameter analysis generates a one-dimensional model identical to a typical one-dimensional model in a special case. The one- and two-dimensional models agree well in the situations examined. When the wall fluxes are of a certain class, the concentration to which the solution tends as the fluid proceeds down the tubule can be computed algebraically.     

The role of flow velocity combined with habitat complexity as a top–down regulator in seagrass meadows

Large‐scale losses of seagrass areas have been associated with eutrophication events, which have led to an overproduction of photosynthetic organisms including epiphytes. Grazers that feed on epiphytes can exert a significant top–down control in the system, but the effects of physical factors on grazing activity and feeding behaviour have been rarely examined. We addressed the combination of hydrodynamic regime and seagrass shoot density can alter the feeding and foraging behaviours of mesograzers. A full factorial experiment, with flow velocity (high, medium and low) and shoot density (high versus low) as main factors, was conducted in a racetrack flume using artificial seagrass plots. The results showed that when high flow velocity conditions were combined with low shoot density, consumption of epiphytes by mesograzers was strongly reduced. In contrast, when flow velocity was low or shoot density was high, mesograzers exhibited high feeding rates and vigorous swimming behaviour. These results clearly indicate that hydrodynamic stress reduces the time that mesograzers can spend feeding, since it inhibits their swimming behaviour, and thus indirectly affecting to the density of epiphytes. Therefore, the triggering of trophic cascade effects in seagrass communities under these experimental conditions depended on the interrelationship and feedbacks among shoot density, abiotic (flow velocity) and biotic (epiphytes and mesograzers) compartments, with flow velocity exerting a top–down control on seagrass ecosystems.     

Initial evidence for simultaneous,bi-directional sap flow in roots of interconnected aspen ramets (<Emphasis Type="Italic">Populus tremuloides</Emphasis>)

Approximately 40% of the world’s currently known plant species exhibit some form of clonality. Yet, little is known about the extent of clonal integration (e.g. the sharing and translocation of resources among ramets), especially in woody species. Aspen (Populus tremuloides Michx.), a widespread clonal tree species of high ecological value and conservation concern, is an excellent model species to study clonal integration. We used sap flow sensors on the root system of aspen located in the Fraser Experimental Forest (Colorado) to quantify water fluxes, assess directionality of flow and assess responses to a root severing experiment. Our results indicate simultaneous, bi-directional flow in roots with 3–4 times more flow in one direction. Flow towards ramets that were subjected to severing of roots (except the measured root) decreased considerably, and an increase in root flow ‘down the line’ towards connected, untreated ramets suggests complex interactions within the root system. Our results are intriguing and provide a first account of directionality of flow and distribution of water in an interconnected root system of a clonal tree species. Based on these findings, we formulate a set of further research questions and discuss methodology and experiments to test them.     

Measuring opening pressure in lumbar puncture--a new method]

Determination of the opening pressure (OP) during diagnostic lumbar puncture (LP) yields additional information that may impact on treatment and prognosis in disorders affecting the central nervous system (e.g. meningitis). Established methods contain systematic errors as well as risks to the patient. We therefore present a new procedure that allows measurement of the OP by timing the flow of cerebrospinal fluid through a capillary attached to an LP needle. A resistance located between needle and capillary slows down the flow of cerebrospinal fluid so that it becomes independent of the capillary forces acting on it. The time required for the fluid to travel between two marks on the capillary (defining a given volume) can be used to calculate the flow. Since the combined resistance of needle and resistance can be calibrated, the pressure driving the flow--in this case the opening pressure--can be calculated. A simple model was used to evaluate the impact of different resistances and different needles on OP determination. The effects of cellular elements and proteins in the CSF are discussed.     

Mechanisms of breathing instability in patients with obstructive sleep apnea.

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 +/- 24 h(-1)) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following approximately 30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5(th) breath following administration of 6% CO(2) combined with approximately 4% desaturation, was large (187 +/- 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.     

The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers

We compared rates of oxygen transport in an in vitro capillary system using red blood cells (RBCs) and cell-free hemoglobins. The axial PO(2) drop down the capillary was calculated using finite-element analysis. RBCs, unmodified hemoglobin (HbA(0)), cross-linked hemoglobin (alpha alpha-Hb) and hemoglobin conjugated to polyethylene-glycol (PEG-Hb) were evaluated. According to their fractional saturation curves, PEG-Hb showed the least desaturation down the capillary, which most closely matched the RBCs; HbA(0) and alpha alpha-Hb showed much greater desaturation. A lumped diffusion parameter, K*, was calculated based on the Fick diffusion equation with a term for facilitated diffusion. The overall rates of oxygen transfer are consistent with hemoglobin diffusion rates according to the Stokes-Einstein Law and with previously measured blood pressure responses in rats. This study provides a conceptual framework for the design of a 'blood substitute' based on mimicking O(2) transport by RBCs to prevent autoregulatory changes in blood flow and pressure.     

Flow modeling in a novel non-perfusion conical bioreactor

We have developed a bioreactor vessel design which has the advantages of simplicity and ease of assembly and disassembly, and with the appropriately determined flow rate, even allows for a scaffold to be suspended freely regardless of its weight. This article reports our experimental and numerical investigations to evaluate the performance of a newly developed non-perfusion conical bioreactor by visualizing the flow through scaffolds with 45 degrees and 90 degrees fiber lay down patterns. The experiments were conducted at the Reynolds numbers (Re) 121, 170, and 218 based on the local velocity and width of scaffolds. The flow fields were captured using short-time exposures of 60 microm particles suspended in the bioreactor and illuminated using a thin laser sheet. The effects of scaffold fiber lay down pattern and Reynolds number were obtained and correspondingly compared to results obtained from a computational fluid dynamics (CFD) software package. The objectives of this article are twofold: to investigate the hypothesis that there may be an insufficient exchange of medium within the interior of the scaffold when using our non-perfusion bioreactor, and second, to compare the flows within and around scaffolds of 45 degrees and 90 degrees fiber lay down patterns. Scaffold porosity was also found to influence flow patterns. It was therefore shown that fluidic transport could be achieved within scaffolds with our bioreactor design, being a non-perfusion vessel. Fluid velocities were generally same of the same or one order lower in magnitude as compared to the inlet flow velocity. Additionally, the 90 degrees fiber lay down pattern scaffold was found to allow for slightly higher fluid velocities within, as compared to the 45 degrees fiber lay down pattern scaffold. This was due to the architecture and pore arrangement of the 90 degrees fiber lay down pattern scaffold, which allows for fluid to flow directly through (channel-like flow).     

Cell differentiation based on absorption and scattering.

Improvements of the flow system allow calibrated cell length measurements down to less than 2 micron at a very high rate. An optical index match to plane viewing windows perpendicular to the optical axis in the flow system keeps the axial symmetry for forward scattered light. Cell size, axial light loss and scattering intensity within different angles were found to be powerful tools to differentiate cell populations. Red cells were analyzed according to various cell surface structures. Lymphocyte populations isolated from different parts of the lymphatic system in rats have been distinguished. Experimental tumor cells showed typical data pattern after different chemical treatments.     

Ultra scale‐down characterization of the impact of conditioning methods for harvested cell broths on clarification by continuous centrifugation—Recovery of domain antibodies from rec E. coli

The processing of harvested E. coli cell broths is examined where the expressed protein product has been released into the extracellular space. Pre‐treatment methods such as freeze–thaw, flocculation, and homogenization are studied. The resultant suspensions are characterized in terms of the particle size distribution, sensitivity to shear stress, rheology and solids volume fraction, and, using ultra scale‐down methods, the predicted ability to clarify the material using industrial scale continuous flow centrifugation. A key finding was the potential of flocculation methods both to aid the recovery of the particles and to cause the selective precipitation of soluble contaminants. While the flocculated material is severely affected by process shear stress, the impact on the very fine end of the size distribution is relatively minor and hence the predicted performance was only diminished to a small extent, for example, from 99.9% to 99.7% clarification compared with 95% for autolysate and 65% for homogenate at equivalent centrifugation conditions. The lumped properties as represented by ultra scale‐down centrifugation results were correlated with the basic properties affecting sedimentation including particle size distribution, suspension viscosity, and solids volume fraction. Grade efficiency relationships were used to allow for the particle and flow dynamics affecting capture in the centrifuge. The size distribution below a critical diameter dependant on the broth pre‐treatment type was shown to be the main determining factor affecting the clarification achieved. Biotechnol. Bioeng. 2014;111: 913–924. © 2013 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.     

Anatomically based finite element models of the human pulmonary arterial and venous trees including supernumerary vessels.

Studies of the origin of pulmonary blood flow heterogeneity have highlighted the significant role of vessel branching structure on flow distribution. To enable more detailed investigation of structure-function relationships in the pulmonary circulation, an anatomically based finite element model of the arterial and venous networks has been developed to more accurately reflect the geometry found in vivo. Geometric models of the arterial and venous tree structures are created using a combination of multidetector row X-ray computed tomography imaging to define around 2,500 vessels from each tree, a volume-filling branching algorithm to generate the remaining accompanying conducting vessels, and an empirically based algorithm to generate the supernumerary vessel geometry. The explicit generation of supernumerary vessels is a unique feature of the computational model. Analysis of branching properties and geometric parameters demonstrates close correlation between the model geometry and anatomical measures of human pulmonary blood vessels. A total of 12 Strahler orders for the arterial system and 10 Strahler orders for the venous system are generated, down to the equivalent level of the terminal bronchioles in the bronchial tree. A simple Poiseuille flow solution, assuming rigid vessels, is obtained within the arterial geometry of the left lung, demonstrating a large amount of heterogeneity in the flow distribution, especially with inclusion of supernumerary vessels. This model has been constructed to accurately represent available morphometric data derived from the complex asymmetric branching structure of the human pulmonary vasculature in a form that will be suitable for application in functional simulations.     

Arterial flow under periodic body acceleration

The present study deals with the effect of externally-imposed body accelerations on blood flow in arteries. Body accelerations may be caused deliberately, for example making the subjecs lie down on vibrating tables: or unintentionally during travel in road vehicles, aircraft or spacecraft. A mathematical model of flow in single arteries subject to a pulsating pressure gradient as well as body acceleration is presented. The resulting equations are solved by using the technique of Laplace transforms. Computational results are presented for the effects of body accelerations on flow variables namely flow rate, velocity of flow, acceleration and shear stress corresponding to typical arteries of human subjects.     

Functional hierarchy of coronary circulation: direct evidence of a structure-function relation

The heart muscle is nourished by a complex system of blood vessels that make up the coronary circulation. Here we show that the design of the coronary circulation has a functional hierarchy. A full anatomic model of the coronary arterial tree, containing millions of blood vessels down to the capillary vessels, was simulated based on previously measured porcine morphometric data. A network analysis of blood flow through every vessel segment was carried out based on the laws of fluid mechanics and appropriate boundary conditions. Our results show an abrupt change in cross-sectional area that demarcates the transition from epicardial (EPCA) to intramyocardial (IMCA) coronary arteries. Furthermore, a similar pattern of blood flow was observed with a corresponding transition from EPCA to IMCA. These results suggest functional differences between the two types of vessels. An additional abrupt change occurs in the IMCA in relation to flow velocity. The velocity is fairly uniform proximal to these vessels but drops significantly distal to those vessels toward the capillary branches. This finding suggests functional differences between large and small IMCA. Collectively, these observations suggest a novel functional hierarchy of the coronary vascular tree and provide direct evidence of a structure-function relation.     

Functional Imaging of Plants: A Nuclear Magnetic Resonance Study of a Cucumber Plant

Functional magnetic resonance imaging was used to study transients of biophysical parameters in a cucumber plant in response to environmental changes. Detailed flow imaging experiments showed the location of xylem and phloem in the stem and the response of the following flow characteristics to the imposed environmental changes: the total amount of water, the amount of stationary and flowing water, the linear velocity of the flowing water, and the volume flow. The total measured volume flow through the plant stem was in good agreement with the independently measured water uptake by the roots. A separate analysis of the flow characteristics for two vascular bundles revealed that changes in volume flow of the xylem sap were accounted for by a change in linear-flow velocities in the xylem vessels. Multiple-spin echo experiments revealed two water fractions for different tissues in the plant stem; the spin-spin relaxation time of the larger fraction of parenchyma tissue in the center of the stem and the vascular tissue was down by 17% in the period after cooling the roots of the plant. This could point to an increased water permeability of the tonoplast membrane of the observed cells in this period of quick recovery from severe water loss.     

Convective diffusion in parallel flow fields

Laminar motion of two viscous incompressible fluids through each other is treated for two cases: flow along the axis of a circular cylinder, and flow between parallel flat plates. Motion of either fluid entails that of the other. Regarding one fluid as a solvent, the other as a solute, and supposing the system to have ends impermeable to the former, it is found that the solvent streams with the solute down the center of the system, to return in the opposite direction out nearer the walls. Thus diffusion of a dissolved substance through a region in which the solvent is confined produces continual streaming in the latter.     

Analysis of micromolar concentrations of glucose by an interference free flow injection based biosensor

A fast, sensitive, interference-free, single enzyme single reagent glucose biosensor, operated in flow injection analysis (FIA) mode, was developed. The method used involved formation of colored complex of titanium sulfate reagent with the peroxide generated by glucose oxidase immobilized in a packed bed reactor. The color developed was detected spectrophotometrically in a flow cuvette. The system could measure down to 0.5 mg glucose l^–1 and the response was reproducible and linear in the range 1 mg l^–1 to 100 mg l^–1. The analysis time for a 500 l sample was 35 s and was free of interference from a number of substances tested. Analysis results using an off-line batch kit were observed to be in agreement with the developed system for determination of glucose in blood plasma samples.     

An electromechanical hypothesis for ciliary coordination in ciliated protozoa

A new electrochemical hypothesis is proposed to explain ciliary coordination. The hypothesis states that, whenever a cilium beats, the membrane immediately surrounding the cilium is strained. The strain allows a local increase in ionic permeability so ions may flow down an electrochemical gradient and trigger activity in nearby cilia not in a refractory state.     

Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.

The introduction of stochastic methods in pedigree analysis has enabled geneticists to tackle computations intractable by standard deterministic methods. Until now these stochastic techniques have worked by running a Markov chain on the set of genetic descent states of a pedigree. Each descent state specifies the paths of gene flow in the pedigree and the founder alleles dropped down each path. The current paper follows up on a suggestion by Elizabeth Thompson that genetic descent graphs offer a more appropriate space for executing a Markov chain. A descent graph specifies the paths of gene flow but not the particular founder alleles traveling down the paths. This paper explores algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis. Realistic numerical examples demonstrate the feasibility of the algorithms.