坪田 健一

Abstract Living tissues exhibit complex mechanical properties, including viscoelastic and elastoplastic responses, that are crucial for regulating cell behaviors and tissue deformations. Despite their significance, the intricate properties of three-dimensional (3D) multicellular tissues are not well understood and are inadequately implemented in biomaterial engineering. To address this gap, we developed a numerical method to analyze the dynamic properties of multicellular tissues using a 3D vertex model framework. By focusing on 3D tissues composed of confluent homogeneous cells, we characterized their properties in response to various deformation magnitudes and time scales. Stress relaxation tests revealed that large deformations initially induced relaxation in the shapes of individual cells. This process is amplified by subsequent transient cell rearrangements, homogenizing cell shapes and leading to tissue fluidization. Additionally, dynamic viscoelastic analyses showed that tissues exhibited strain softening and hysteresis during large deformations. Interestingly, this strain softening originates from multicellular structures independent of cell rearrangement, while hysteresis arises from cell rearrangement. Moreover, tissues exhibit elastoplastic responses over the long term, which are well represented by the Ramberg–Osgood model. These findings highlight the characteristic properties of multicellular tissues emerging from their structures and rearrangements, especially during long-term large deformations. The developed method offers a new approach to uncover the dynamic nature of 3D tissue mechanics and could serve as a technical foundation for exploring tissue mechanics and advancing biomaterial engineering.

A numerical simulation was carried out to investigate the blood flow behavior (i.e., flow rate and pressure) and coupling of a renal vascular network and the myogenic response to various conditions. A vascular segment and an entire kidney vascular network were modeled by assuming one single vessel as a straight pipe whose diameter was determined by Murray’s law. The myogenic response was tested on individual AA (afferent artery)–GC (glomerular capillaries)–EA (efferent artery) systems, thereby regulating blood flow throughout the vascular network. Blood flow in the vascular structure was calculated by network analysis based on Hagen–Poiseuille’s law to various boundary conditions. Simulation results demonstrated that, in the vascular segment, the inlet pressure Pinlet and the vascular structure act together on the myogenic response of each individual AA–GC–EA subsystem, such that the early-branching subsystems in the vascular network reached the well-regulated state first, with an interval of the inlet as Pinlet = 10.5–21.0 kPa, whereas the one that branched last exhibited a later interval with Pinlet = 13.0–24.0 kPa. In the entire vascular network, in contrast to the Pinlet interval (13.0–20.0 kPa) of the unified well-regulated state for all AA–GC–EA subsystems of the symmetric model, the asymmetric model exhibited the differences among subsystems with Pinlet ranging from 12.0–17.0 to 16.0–20.0 kPa, eventually achieving a well-regulated state of 13.0–18.5 kPa for the entire kidney. Furthermore, when Pinlet continued to rise (e.g., 21.0 kPa) beyond the vasoconstriction range of the myogenic response, high glomerular pressure was also related to vascular structure, where PGC of early-branching subsystems was 9.0 kPa and of late-branching one was 7.5 kPa. These findings demonstrate how the myogenic response regulates renal blood flow in vascular network system that comprises a large number of vessel elements.

Three-dimensional computational fluid dynamics (CFD) simulations were performed in the anastomotic region of the Fontan route between the venae cava and pulmonary arteries to investigate the risk of thrombosis due to blood stasis in the Fontan circulation. The finite volume method based on the time-averaged continuity and Navier–Stokes equations combined with the k-ω SST turbulent model was used in the CFD simulations. Low shear rate (SR) and SR on the wall (WSR) of <10 s−1 were used as markers to assess blood stasis as a cause of blood coagulation. Simulated blood flow velocity and both SR and WSR were reduced in the right atrium (RA) as the cavity of a flow channel in the atriopulmonary connection (APC) Fontan model, whereas the values increased in the total cavopulmonary connection (TCPC) Fontan model, which has no cavity. The volume of SR <10 s−1 and wall surface area of WSR <10 s−1 were, respectively, 4.6–261.8 cm3 and 1.2–38.3 cm2 in the APC Fontan model, and 0.1–0.3 cm3 and 0.1–0.6 cm2 in the TCPC Fontan model. The SR and WSR increased in the APC model with a normal-sized RA and the TCPC model as the flow rate of blood from the inferior vena cava increased with exercise; however, the SR and WSR in the RA decreased in the APC model with a dilated RA owing to the development of a recirculating flow. These findings suggest that the APC Fontan has a higher risk of thrombosis due to blood stasis than the TCPC Fontan and a higher RA dilation is associated with a higher risk of thrombosis from a fluid mechanics perspective.

<p>Deformability of epithelial tissues plays a crucial role in embryogenesis, homeostasis, wound healing, and disease. The deformability is determined by the mechanical balance between active force generation and passive response of cells. However, little is known about how multiple cells in epithelial tissues passively respond to external forces. Using a 3D vertex model, we performed computational simulations of longitudinal tension and compression tests of an epithelial tube. Under tension, the tube extended with necking as exhibiting cell rearrangements that play a role in reducing local stiffness of the tube. On the other hand, under compression, the tube buckled with kinking without cell rearrangements. The cell rearrangements occurred when apical and basal cell surfaces stored elastic deformation energies. These results illustrate the variance of deformation modes of epithelial tissues in the single cell level as well as the importance of cell rearrangements in regulating epithelial deformability.</p>

Actomyosin generates contractile forces within cells, which have a crucial role in determining the macroscopic mechanical properties of epithelial tissues. Importantly, actin cytoskeleton, which propagates actomyosin contractile forces, forms several characteristic structures in a 3D intracellular space, such as a circumferential actin belt lining adherence junctions and an actin mesh beneath the apical membrane. However, little is known about how epithelial mechanical property depends on the intracellular contractile structures. We performed computational simulations using a 3D vertex model, and demonstrated the longitudinal tensile test of an epithelial tube, whose inside and outside are defined as the apical and basal surfaces, respectively. As a result, these subcellular structures provide the contrary dependence of epithelial stiffness and fracture force on the spontaneous curvature of constituent cells; the epithelial stiffness increases with increasing the spontaneous curvature in the case of belt, meanwhile it decreases in the case of mesh. This qualitative difference emerges from the different anisotropic deformability of apical cell surfaces; while belt preserves isotropic apical cell shapes, mesh does not. Moreover, the difference in the anisotropic deformability determines the frequency of cell rearrangements, which in turn effectively decrease the tube stiffness. These results illustrate the importance of the intracellular contractile structures, which may be regulated to optimize mechanical functions of individual epithelial tissues.

Although abdominal aortic aneurysms (AAAs) occur mostly inferior to the renal artery, the mechanism of the development of AAA in relation to its specific location is not yet clearly understood. The objective of this study was to evaluate the hypothesis that even healthy volunteers may manifest specific flow characteristics of blood flow and alter wall shear or oscillatory shear stress in the areas where AAAs commonly develop. Eight healthy male volunteers were enrolled in this prospective study, aged from 24 to 27. Phase-contrast magnetic resonance imaging (MRI) was performed with electrocardiographic triggering. Flow-sensitive four-dimensional MR imaging of the abdominal aorta, with three-directional velocity encoding, including simple morphological image acquisition, was performed. Information on specific locations on the aortic wall was applied to the flow encodes to calculate wall shear stress (WSS) and oscillatory shear index (OSI). While time-framed WSS showed the highest peak of 1.14 +/- A 0.25 Pa in the juxtaposition of the renal artery, the WSS plateaued to 0.61 Pa at the anterior wall of the abdominal aorta. The OSI peaked distal to the renal arteries at the posterior wall of the abdominal aorta of 0.249 +/- A 0.148, and was constantly elevated in the whole abdominal aorta at more than 0.14. All subjects were found to have elevated OSI in regions where AAAs commonly occur. These findings indicate that areas of constant peaked oscillatory shear stress in the infra-renal aorta may be one of the factors that lead to morphological changes over time, even in healthy individuals.

A computer simulation was carried out for thrombus formation under the influence of blood flow after Fontan operation. Blood was modeled by computed particles assigned as normal blood or thrombus. Blood flow was calculated using a moving particle semi-implicit method. In a model of blood coagulation that causes thrombi,a normal blood particle changed to a thrombus when its shear rate was lower than a threshold. A spring force was employed to express the coagulation,and was substituted into the NS equations as the external force to couple the coagulation and the blood flow. In simulations,thrombus formation was affected by blood flow behaviors,such as stagnation and recirculation. The atrio-pulmonary connection (APC) square model showed the highest incidence for thrombus formation in the right atrium due to flow stagnation,followed by the APC round,whereas no thrombus was formed in the total cavopulmonary connection model. This result suggests that local hemodynamic behavior associated with the complex channel geometry plays a major role in thrombus formation in the Fontan route.

To understand the mechanism regulating the spontaneous change in polarity that leads to cell turning, we quantitatively analyzed the dynamics of focal adhesions (FAs) coupling with the self-assembling actin cytoskeletal structure in Swiss 3T3 fibroblasts. Fluorescent imageswere acquired fromcells expressing GFP-actin and RFP-zyxin by laser confocal microscopy. On the basis of the maximum area, duration, and relocation distance of FAs extracted from the RFP-zyxin images, the cells could be divided into 3 regions: the front region, intermediate lateral region, and rear region. In the intermediate lateral region, FAs appeared close to the leading edge and were stabilized gradually as its area increased. Simultaneously, bundled actin stress fibers (SFs) were observed vertically from the positions of these FAs, and they connected to the other SFs parallel to the leading edge. Finally, these connecting SFs fused to forma single SF with matured FAs at both ends. This change in SF organization with cell retraction in the first cycle of migration followed by a newly formed protrusion in the next cycle is assumed to lead to cell turning in migrating Swiss 3T3 fibroblasts.

The classical Fontan route, namely the atriopulmonary connection (APC), continues to be associated with a risk of thrombus formation in the atrium. A conversion to a total cavopulmonary connection (TCPC) from the APC can ameliorate hemodynamics for the failed Fontan; however, the impact of these surgical operations on thrombus formation remains elusive. This study elucidates the underlying mechanism of thrombus formation in the Fontan route by using a two-dimensional computer hemodynamic simulation based on a simple blood coagulation rule. Hemodynamics in the Fontan route was simulated with Navier-Stokes equations. The blood coagulation and the hemodynamics were combined using a particle method. Three models were created: APC with a square atrium, APC with a round atrium, and TCPC. To examine the effects of the venous blood flow velocity, the velocity at rest and during exercise (0.5 and 1.0 W/kg) was measured. The total area of the thrombi increased over time. The APC square model showed the highest incidence for thrombus formation, followed by the APC round, whereas no thrombus was formed in the TCPC model. Slower blood flow at rest was associated with a higher incidence of thrombus formation. The TCPC was superior to the classical APC in terms of preventing thrombus formation, due to significant blood flow stagnation in the atrium of the APC. Thus, local hemodynamic behavior associated with the complex channel geometry plays a major role in thrombus formation in the Fontan route.

Microvascular network remodelling is a common denominator for multiple pathologies and involves both angiogenesis, defined as the sprouting of new capillaries, and network patterning associated with the organization and connectivity of existing vessels. Much of what we know about microvascular remodelling at the network, cellular and molecular scales has been derived from reductionist biological experiments, yet what happens when the experiments provide incomplete (or only qualitative) information? This review will emphasize the value of applying computational approaches to advance our understanding of the underlying mechanisms and effects of microvascular remodelling. Examples of individual computational models applied to each of the scales will highlight the potential of answering specific questions that cannot be answered using typical biological experimentation alone. Looking into the future, we will also identify the needs and challenges associated with integrating computational models across scales.

A computational study of effects of vessel dynamics and compliance on coronary artery hemodynamics with/without stenosis is presented. The coronary artery hemodynamics with stenosis has been a main subject as one of the major cardiovascular diseases induced by atherosclerosis most computational models assume that the vessel movement and deformation are negligible (Zeng, et al., 2003 Kim, et al., 2010). However, it is still unclear whether the hemodynamic characteristics owning to vessel dynamics and compliance are clinically significant or not particularly under pathological conditions. In this study, we aim at investigating the hemodynamic effects of the vessel dynamics and compliance in right coronary artery under healthy situation without stenosis as well as under diseased conditions with stenosis. We constructed a three-dimensional geometric model of the right coronary artery based on X-ray angiographic images, in which both vessel movement and deformation were taken into account. A specific volumetric flow rate was employed as a boundary condition imposed on inlet. Furthermore, we carried out an extensive study on the inlet waveform dependence and the effects of the vessel compliance on coronary hemodynamics. Our results demonstrate that the conventional assumption on 'rigid' artery models holds only in the cases of normal coronary arteries but fails for stenosed coronary arteries where the vessel dynamics and compliance do extend significant influence on distributions of the oscillatory shear indices (OSIs). Moreover, we find that the effects of vessel dynamics and compliance on coronary hemodynamics seem to be independent of both inlet boundary conditions and the vessel compliance.

The purpose of this work is developing the injury analysis model that can be expressed liver damage state by the Moving Particle Semi-implicit (MPS) method. In this paper, we set the material properties of the liver by simulating material test using the simplified geometric model that can represent the basic physical phenomena of the viscoelastic body.

With regard to the out-of-plane bending energy of an elastic surface membrane, capsule deformation was compared between Helfrich's isotropic continuum model and discrete models using a triangulated surface. The in-plane deformation of the membrane was modeled by the neo-Hookean or Skalak law. Two mechanical problems were numerically simulated. One was the deformation of a spherical capsule under simple shear flow and the other was the equilibrium shape of a capsule with a nonzero excess surface area, assuming the shape mechanics of a normal red blood cell. The numerical simulations demonstrated that a discrete model based on locally averaged mean curvature satisfactorily reproduces the mechanical behavior determined by Helfrich's isotropic continuum model, whereas a discrete model without the averaging exhibited different deformation behavior. Differences in the mechanical behavior between bending models may cause differences in estimated bending rigidity values of up to one order of magnitude. (C) 2014 Elsevier Inc. All rights reserved.

Direct numerical simulations of the mechanics of a single red blood cell (RBC) were performed by considering the nonuniform natural state of the elastic membrane. A RBC was modeled as an incompressible viscous fluid encapsulated by an elastic membrane. The in-plane shear and area dilatation deformations of the membrane were modeled by Skalak constitutive equation, while out-of-plane bending deformation was formulated by the spring model. The natural state of the membrane with respect to in-plane shear deformation was modeled as a sphere (), biconcave disk shape () and their intermediate shapes () with the nonuniformity parameter , while the natural state with respect to out-of-plane bending deformation was modeled as a flat plane. According to the numerical simulations, at an experimentally measured in-plane shear modulus of and an out-of-plane bending rigidity of of the cell membrane, the following results were obtained. (i) The RBC shape at equilibrium was biconcave discoid for and cupped otherwise; (ii) the experimentally measured fluid shear stress at the transition between tumbling and tank-treading motions under shear flow was reproduced for ; (iii) the elongation deformation of the RBC during tank-treading motion from the simulation was consistent with that from in vitro experiments, irrespective of the value. Based on our RBC modeling, the three phenomena (i), (ii), and (iii) were mechanically consistent for . The condition precludes a biconcave discoid shape at equilibrium (i); however, it gives appropriate fluid shear stress at the motion transition under shear flow (ii), suggesting that a combined effect of and the natural state with respect to out-of-plane bending deformation is necessary for understanding details of the RBC mechanics at equilibrium. Our numerical results demonstrate that moderate nonuniformity in a membrane's natural state with respect to in-plane shear deformation plays a key role in RBC mechanics.

Aortic aneurysms may cause the turbulence of blood flow and result in the energy loss of the blood flow, while grafting of the dilated aorta may ameliorate these hemodynamic disturbances, contributing to the alleviation of the energy efficiency of blood flow delivery. However, evaluating of the energy efficiency of blood flow in an aortic aneurysm has been technically difficult to estimate and not comprehensively understood yet. We devised a multiscale computational biomechanical model, introducing novel flow indices, to investigate a single male patient with multiple aortic aneurysms. Preoperative levels of wall shear stress and oscillatory shear index (OSI) were elevated but declined after staged grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and 0.221 (second operation). Graftings may strategically counter the loss of efficient blood delivery to improve hemodynamics of the aorta. The energy efficiency of blood flow also improved postoperatively. Novel indices of pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation), respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831. Graftings contributed not only to ameliorate wall shear stress or oscillatory shear index but also to improve efficient blood flow. This patient-specific modeling will help in analyzing the mechanism of aortic aneurysm formation and may play an important role in quantifying the energy efficiency or loss in blood delivery.

Actin, a cytoskeletal protein, gathers and polymerizes under the cell membrane to mediate protrusion of the cell membrane. Therefore, actin participates greatly in cell movement. To quantitatively evaluate actin's dynamics during cell protrusion, movements of actin-labeled cells were observed under a confocal laser scanning microscopy, and time-lapse images were obtained. Image analysis of the orientation of actin stress fibers revealed dynamic formation of a meshwork of stress fibers in the protrusion structure at the leading edge of the motile cell. In addition, a number of immobile spots such as focal adhesions were observed adjacent to the dynamic meshwork of stress fibers. The distribution and the time between appearance and disappearance of each spot were analyzed. The results suggest that immobile spots close to the centroid of the cell play a crucial role in providing anchorage and driving cell movement. © 2014 The Institute of Electrical Engineers of Japan.

Leukocytes can rapidly migrate virtually within any substrate found in the body at speeds up to 100 times faster than mesenchymal cells that remain firmly attached to a substrate even when migrating. To understand the flexible migration strategy utilized by leukocytes, we experimentally investigated the three-dimensional modulation of cortical plasticity during the formation of pseudopodial protrusions by mouse leukocytes isolated from blood. The surfaces of viable leukocytes were discretely labeled with fluorescent beads that were covalently conjugated with concanavalin A receptors. The movements of these fluorescent beads were different at the rear, central, and front surfaces. The beads initially present on the rear and central dorsal surfaces of the cell body flowed linearly toward the rear peripheral surface concomitant with a significant collapse of the cell body in the dorsal-ventral direction. In contrast, those beads initially on the front surface moved into a newly formed pseudopodium and exhibited rapid, random movements within this pseudopodium. Bead movements at the front surface were hypothesized to have resulted from rupture of the actin cytoskeleton and detachment of the plasma membrane from the actin cytoskeletal cortex, which allowed leukocytes to migrate while being minimally constrained by a substrate. (C) 2013 Elsevier Inc. All rights reserved.

The purpose of this study was to evaluate the effects of stenosis geometry on primary thrombogenesis with respect to the dynamics of the blood flow. A two-dimensional computer simulation was carried out to simulate the formation of a primary thrombus under blood flow in two geometrically different blood vessels: one straight and the other stenosed. In the simulation, blood was modeled by particles that have characteristics of plasma and of platelets. Plasma and platelet flow was analyzed using the Moving Particle Semi-implicit (MPS) method, while the motion of adhered and aggregated platelets was expressed by mechanical spring forces. With these models, platelet motion in the flowing blood and platelet aggregation and adhesion were successfully coupled with viscous blood flow. The results of the simulation demonstrated that the presence of a stenosis induced changes in blood flow and thereby altered the formation, growth, and destruction of a thrombus. In particular, whereas in the absence of stenosis, the thrombus evenly covered the injured site, in the presence of a stenosis, thrombus formation was skewed to the downstream side. The number of platelets that adhered to the injured site increased earlier as the stenosis became more severe. These results suggest that dynamic changes in blood flow due to the presence of a stenosis affect primary thrombogenesis.

Aiming at establishing a simulation-based framework for predictive medicine we have developed a patient-specific aortic aneurysm model based on computational biomechanics. In this study, we construct two image-based three-dimensional patient-specific models of aortic aneurysms based on CT images of two patients. A multi-scale hemodynamic model is employed to couple these three-dimensional models with a closed-loop 0-1-dimension hemodynamic model for the whole cardiovascular system. The aortic aneurysm hemodynamics are then visualized in terms of streamlines, wall shear stresses and oscillatory shear index, and further analyzed with a specific focus on the relationship between the hemodynamics and the occurrence of the aortic aneurysm.

Here we present a study on three-dimensional shape optimization of flapping wings. A vertical force maximization problem for insect flight is formulated in the domain of unsteady-state, low Reynolds number viscous flow field. Adjoint method, a type of sensitivity analysis based on the variational principle, is modeled by the Navier-Stokes equations and discretized with the finite volume method. With the method, shape optimization of the wings of a model fruit fly in hovering flight is attempted. Rectangles, having both the aspect ratios and the surface areas identical to those of the realistic wings, are taken as the initial shapes. As a result, their sensitivities to the shape modifications are derived.

This study attempted modeling of fibrin network formation process in red thrombus with a two-dimensional particle method simulation of blood flow between parallel plates. Blood flow simulations were carried out based on the two different models of fibrin formation. The first model assumed fibrin formation according to the elapsed time with respect to platelet aggregation. A simulation result on this model demonstrated that fibrin began to form near the injured blood vessel wall where the platelet aggregation was assumed to occur, and that this led to formation of firm thrombus by platelets and fibrin. The second model assumed fibrin formation according to the blood flow. In this case, fibrin began to form near the surface of already aggregated platelets. Because stiffer fibrin formed on softer platelet thrombus, the platelet thrombus that formed at an initial stage of simulation collapsed. After the collapse fibrin adhered to the injured vessel wall, leading to formation of firm thrombus as well as in the first model.

We have developed an insect-size X-wing flapping Micro Air Vehicle (MAV) with a body-length of approximately 6 cm. To quantify the aerodynamic performance of the MAV with a specific focus on the clap and fling mechanism we measured the thrust/lift forces in tethered and free (level) flights. Our tethered flight results show that the MAV is capable to create a thrust force 1.3 times greater than its weight. In the free (level) flight, the stroke plane angle is observed to be around 45 degrees corresponding with a flapping frequency of approximately 25 Hz. Furthermore, we find that the MAV is able to perform the level flight when a static thrust produced is over 0.8 times its weight and that appropriate flexibility of the wing can be a crucial factor in affecting the thrust production to keep it stay on airborne.

A numerical study of hydrodynamics and maneuverability of Zebra fish free swimming is presented. Unsteady hydrodynamics around an undulatory swimming body is solved using an integrated modeling method combining a 3D Computational Fluid Dynamics (CFD) method and a Computational Swimming Dynamics (CSD) method. A larva fish, zebrafish and Danio rerio is modeled, which "swims" by sending a laterally compressing, sinusoidal wave down the tail tip. Hydrodynamics of the 3D larva fish model in terms of the burst, the cyclic and the coast swimming modes were then analyzed and compared with experimental data. Our results present a sequence of 3D vortex structures in free swimming and its relationship with the swimming maneuverability of zebra fishes. This provides a general understanding of the relationship between the dynamic vortex flow and the energetic in terms of output power associated with the undulatory locomotion of vertebrates.

In the last decade, desired to be capable of performing missions such environmental monitoring, surveillance, and assessment in hostile environments MAVs have become a rapidly increasing hot topic. MAVs have a maximal dimension of 15 cm and nominal flight speeds of round 10 m/s, which are comparable with natural flyers of birds. bats and insects in size. Flapping flight of birds and insects often shows fascination aerodynamic performance in terms of acceleration and quick turning even in dust and is the main subject till now. However, there are still very few studies associated with the flapping-wing control system. In this project, I am aiming at building up an ornithopter with an integrated control system containing posture sensors, GPS, and microcomputer, etc and hope to establish a specific autonomy flight control system for flapping-wing MAVs.

Insect flapping flight can offer some novel mechanisms useful in designing MAVs (Micro Air Vehicles), a flyer with a maximal dimension of 15 cm. There have been many fascinating works done on the biological flights of moth, fly, bee and so forth in the last decade, but still very few is found about butterflies. Butterflies have low aspect-ratio wings and low wing beat frequencies, but in general exhibit apparently pitching oscillations vertically during flapping flight. Additionally, they change the wing areas during flapping flight, which is called wing-morphing. In this study, aiming at providing a comprehensive study on aerodynamic mechanisms in butterfly flights we have carried out a CFD-based numerical simulation of flapping flight in butterfly on a basis of realistic wing-body geometry and wing kinematics.

We propose a numerical method for simulating three-dimensional hemodynamics arising from malaria-infection. Malaria-infected red blood cells (IRBCs) become stiffer and develop the property of cytoadherent and resetting. To clarify the mechanism of microvascular obstruction in malaria, we need to understand the changes of hemodynamics, involving interaction between IRBC, healthy RBCs, and endothelial cells. In the proposed model, all the components of blood are represented by a finite number of particles. The membrane of RBCs is expressed by two-dimensional network. Malaria parasites inside the RBC are represented by solid objects. The motion of each particle is described by the conservation laws of mass and momentum for incompressible fluid. We examine several numerical tests, involving the stretching of IRBCs, and flow in narrow channels, to validate our model. The obtained results agree well with the experimental results. Our method would be helpful for further understandings of pathology of malaria-infection.

It is known that conventional aerodynamic theories do not work for micro air vehicles (MAVs); and the low-Reynolds number aerodynamics in particular relating to flight mechanisms of insects and birds has been an active and interdisciplinary area. We have developed two types of four-winged prototype ornithopters. One has the "X-wings" similar to the Delfly (upper left wing and lower right are connected, so are lower left and upper right), whereas the other has the "Double L-wings" (upper and lower ipsilateral wing flap together while maintaining a right angle). The X-wings 'clap and fling' at both sides of the body; the Double L-wings clap and fling above the body. In this study we show experimental results on the aerodynamic performances of the two vehicles and further discuss how the transmission mechanism affects the force generation.

Humming birds usually show similar features in size and flapping wing kinematics compared with insects but discrepancy in aerodynamic performance. In this study, we construct a realistic morphological and kinematic model of rufous hummingbird (Selasphorus rufus) for the computational fluid dynamic (CFD) study of hovering aerodynamics. We present results of the near-and far-field vortex flow structures around the animal in hovering, and further discuss about their relationship with the lift generation mechanisms.

Recently, significance of left ventricular-arterial (VA) coupling has been frequently stressed in studies concerning aging and hypertension. In this study, we construct an integrated computational biomechanical model of the left ventricle and the major arteries in terms of the multi-scale computation of the whole-body circulatory system. We have this image-based three-dimensional model coupled with the 0-1-dimension models and a physiological model. Using the coupled model, we offer an integrated investigation on the ventricular-arterial (VA) interaction with a focus on hemodynamic features at bifurcations.

Insects are master in maneuvering. Here we present an integrated study of flapping flight stability in a forward flight of hawkmoth by combing a biology-inspired dynamic flight simulator and a recently developed optimal algorithm for flapping wing kinematics. We first compute the vortex flows around a wing-body hawkmoth model, the aerodynamic forces including the lift and drag as well as three moment components. Then, an optimal algorithm is introduced to optimize the flapping wing kinematics so as to realize a trimmed (or balanced) flapping flight mode that the lift is exactly equal to the weight while the drag vanishes at a constant, low and/or high flight speed including hovering. The computed results are compared with experimental data and validated to be reasonable; our results indicate that small variation in flapping wing kinematics may lead to significant change in the force generation.

A numerical study of dynamic flight stability of a hovering hawkmoth and fruitfly are presented, respectively. The method of computational fluid dynamics (CFD) is used to compute the aerodynamic derivatives of the aerodynamic forces and pitching moment in response with a series of small disturbances and the techniques of eigenvalue and eigenvector analysis is used for solving the equations of motion. In the longitudinal disturbance motion, three natural modes are identified which indicates that a hawkmoth hovering flight is stable, while a fruitfly hovering flight is unstable. In addition, the time-response analysis of the simulation is shown here, which indicates the trajectory of the disturbance values in respect of time.

The blood flow dynamics in microcirculation depends strongly on the motion, deformation and interaction of RBCs within the microvessel. This paper presents the application of a confocal micro-PTV system to track RBCs through a circular polydimethysiloxane (PDMS) microchannel. This technique, consists of a spinning disk confocal microscope, high speed camera and a diode-pumped solid state (DPSS) laser combined with a single particle tracking (SPT) method. By using this system detailed motions of individual RBCs were measured at a microscale level. Our results showed that this technique can provide detailed information about microscale disturbance effects caused by RBCs in flowing blood.

Detailed knowledge on the motions and interactions of individual blood cells flowing in microchannels is essential to provide a better understanding on the blood rheological properties and disorders in microvessels. This paper presents the ability of a confocal micro-PTV system to track red blood cells (RBCs) through a 100 μm circular glass microchannel. The technique consists of a spinning disk confocal microscope, high speed camera and a diode-pumped solid state (DPSS) laser combined with a single particle tracking (SPT) software (MtrackJ). Detailed measurements on the motions of RBCs were measured at different haematocrits (Hct). Our results show clearly that this technique can provide detailed information about microscale disturbance effects caused by the blood cells.<BR>1) Goldsmith, H.: Red cell motions and wall interactions in tube flow, Federation Proceedings, Vol. 30, No.5 (1971) pp. 1578-1588.<BR>2) Goldsmith, H. and Marlow J.: Flow behavior of erythrocytes. 11. Particles motions in concentrated suspensions of ghost cells, Journal of Colloid and Interface Science, Vol. 71, No. 2 (1979) pp. 383-407.<BR>3) Lima, R., et al.: Confocal micro-PIV measurements of three dimensional profiles of cell suspension flow in a square microchannel, Meas. Sci. Tech., Vol. 17, (2006) pp. 797-808.<BR>4) Lima, R., et al., In vitro confocal micro-PIV measurements of blood flow in a square microchannel: the effect of the haematocrit on instantaneous velocity profiles, J. Biomech., (in press).<BR>5) Abramoff, M., et al.: Image processing with lmageJ, Biophotonics International, Vol. 11, No. 7 (2004) pp. 36-42.<BR>6) Meijering, E., et al.: Tracking in Molecular Bioimaging, , IEEE Signal Processing Magazine, Vol 23. No. 3 (2006) pp. 46-53.

To solve an aging problem in the society, it is important that the aged people are encouraged to be independent and spend healthy life. We have proposed the concept of the Hyper Hospital, which is the information support system for patients. In the Hyper Hospital, some units analyze their vital data, and patient's family who lives in the distance, the neighborhood and their doctor share the analyzed data through computer network to know their health condition. In this paper, we present a wearable platform for monitoring health condition. This platform sends the analyzed biomedical signal of a patient to a database server in his/her house. We developed a sensor module to acquire EMG that informs weakening of muscular strength by an underexercise or disease such as a hemiplegia. We confirmed that the sensor module works well with storage module and analysis module through some experiment. We also developed a database server for collecting data from any other sensor module and processing the data from each module separately. The proposed system will be expected monitoring health condition of the elderly.

Malaria is one of the most serious diseases for all around the world. It is thought that severe symptoms are caused by microvasucular occlusions of parasitized red blood cells (PRBC) that have adhesive property and low deformability. However, the detailed mechanisms of the vascular occlusion caused by red blood cells are still not clear. In this study, the malaria-infected blood is modeled by particles. The adhesive property of PRBC is expressed by local spring. The result shows that the PRBC interacts with some healthy RBCs and move downstream keeping attachment to the vessel wall. This phenomenon induces the high resistance to the flow, which is likely to lead to microvascular obstruction in lower shear flow.

Variations in both spatial and temporal scales must be considered to fully understand cardiovascular diseases. Given these considerations, we investigated the cardiovascular system from the micro- to macroscale using computational biomechanics. This paper presents our findings on mass transport in cerebral aneurysms, platelet aggregation in blood flow, and a particle method for computing microcirculation. Ultimately, these models will help to clarify the biological phenomena surrounding disease processes and will provide a framework for integrating future developments in understanding macro- and microscale biomechanics.

To study the microcirculation for the analysis of thrombosis and haemolytic anaemia, fluid (plasma) flow and the motion of cellular components such as the red blood cell (RBC) and platelets must be included in the model. Vascular wall should also be included when the mechanical and biological interactions between the wall and cells are of concern. In the microvascular region, the cells and the plasma must be separately modeled because the length scale of the cellular components is comparable, sometimes larger, than the vascular diameter. To model the mechanical interactions between the cell and the wall, including their collisions, highly deformable nature of the cellular membrane must be represented in the model. In this study, a new computer simulation using particle method was proposed to analyze microscopic behavior of blood flow. A simulation region including plasma, red blood cells (RBCs) and platelets was modeled by an assembly of discrete particles. The proposed method was applied to the motion and deformation of single RBC and multiple RBCs, and the thrombogenesis process due to platelet aggregation.