Y. Imai

Low voltage pulses can induce apoptosis

Electroporation is used for gene transfection, drug delivery, and cell fusion. While studies have shown that high voltage electroporation induces apoptosis in vitro, a strong electric field can lower cell survival rates. As there are no published reports which have examined apoptotic properties associate with low voltage electric charges, we demonstrated for the first time that consecutive low voltage pulses with a voltage lower than the membrane breakdown threshold of human cells can increase the membrane potential to the threshold required to induce electroporation. This led to apoptosis through caspase pathways. Moreover, necrotic cell damage was less than that caused by high voltage pulses. Therefore, low voltage electroporation can be a suitable anticancer method.

Transport phenomena of microbial flora in the small intestine with peristalsis.

The gastrointestinal tract of humans is colonized by indigenous prokaryotic and eukaryotic microbial cells that form a complex ecological system called microbial flora. Although the microbial flora has diverse functions, its homeostasis inside the gastrointestinal tract is still largely unknown. Therefore, creating a model for investigating microbial flora in the gastrointestinal tract is important. In this study, we developed a novel numerical model to explore the transport phenomena of microbial flora in the small intestine. By simultaneously solving the flow field generated by peristalsis, the concentrations of oxygen and nutrient, and the densities of moderate anaerobes and aerobes, the effects of fluid mechanics on the transport phenomena of microbial flora are discussed. The results clearly illustrated that fluid mechanics have considerable influence not only on the bacterial population, but also on the concentration distributions of oxygen and nutrient. Especially, the flow field enhances the radial variation of the concentration fields. We also show scaling arguments for bacterial growth and oxygen consumption, which capture the main features of the results. Additionally, we investigated the transport phenomena of microbial flora in a long tube with 40 constrictions. The results showed a high growth rate of aerobes in the upstream side and a high growth rate of anaerobes in the downstream side, which qualitatively agrees with experimental observations of human intestines. These new findings provide the fundamental basis for a better understanding of the transport phenomena of microbial flora in the intestine.

Development of a wearable surveillance system using gait analysis

An aging society is a reality in developed countries. An aging population requires more healthcare workers and facilities. To reduce this social problem, it is worthwhile to develop a wearable computer for elders or patients to watch over them. In this study, we developed a wearable computer, in which accelerometers were installed to detect variations of posture, falls, and gait disability. The advantages of this system include a designated database server in each patients home, scalability and flexibility to adapt to patients needs, and full patient access to their own information. As a first step, we adopted this system for healthy young volunteers with or without impediments to validate the system. The results show that this system can successfully detect variations in posture and falls. We also succeeded in real-time automatic gait analysis by using the Hampering Index. The present study gives useful knowledge for the development of a wearable computer to support the care of elders or other patients.

A realistic simulation of saccular cerebral aneurysm formation: focussing on a novel haemodynamic index, the gradient oscillatory number

Although how cerebral aneurysms initiate and grow is still unclear, haemodynamics is thought to play an important role. In order to better understand the aneurysm formation mechanism, we performed a computational analysis of aneurysm formation for a patient-specific arterial geometry. First, CFD was used to perform a pulsatile blood flow analysis and calculate a novel haemodynamic index, the gradient oscillatory number (GON). Then, using aneurysm growth model in which the proliferation of the wall was hypothesised, we performed an aneurysm formation analysis based on the GON index distribution. The result showed that a saccular cerebral aneurysm could appear based on our hypothesis for a patient-specific arterial geometry. On the other hand, a saccular aneurysm was not observed when assuming only strength degradation of the wall. Our findings have suggested that an arterial biological process, such as the proliferation of the wall, may play a vital role in saccular aneurysm formation.

Lateral migration of a capsule in a parabolic flow

Red blood cells migrate to the center of the blood vessel in a process called axial migration, while other blood cells, such as white blood cells and platelets, are disproportionately found near the blood vessel wall. However, much is still unknown concerning the lateral migration of cells in the blood; the specific effect of hydrodynamic factors such as a wall or a shear gradient is still unclear. In this study, we investigate the lateral migration of a capsule using the boundary integral method, in order to compute exactly an infinite computational domain for an unbounded parabolic flow and a semi-infinite computational domain for a near-wall parabolic flow in the limit of Stokes flow. We show that the capsule lift velocity in an unbounded parabolic flow is linear with respect to the shear gradient, while the lift velocity in a near-wall parabolic flow is dependent on the distance to the wall. Then, using these relations, we give an estimation of the relative effect of the shear gradient as a function of channel width and distance between the capsule and the wall. This estimation can be used to determine cases in which the effect of the shear gradient or wall can be neglected; for example, the formation of the cell-free layer in blood vessels is determined to be unaffected by the magnitude of the shear gradient.

Nodal cilia-driven flow: Development of a computational model of the nodal cilia axoneme

Cilia-driven nodal flow is important in the determination of left-right asymmetry in the body. Several theoretical and computational models have been proposed to explain the mechanics of ciliary motion, although the full mechanism remains unknown. Here, we developed a three-dimensional nodal cilia axoneme model using a finite element-boundary element coupling method, and investigated the mechanics of nodal ciliary motion. We found that the rotational orbit was strongly dependent on the dynein activation frequency. We also investigated flow field generated by the ciliary rotation, and the flow strength decayed as r-3 at the far field from the cilium. Our numerical results also suggest that experimentally observed tilt angle θ=2π/9 is sufficiently large to make a leftward flow. These findings are helpful in better understanding ciliary motion and nodal flow.

Structure of outer arm dynein molecule in respiratory cilia suggests an alternative mechanism of force generation

Background Cilia are microtubule (MT)-based organelles that extend from the surface of eukaryotic cells. The ciliary movement is generated by microtubule (MT) sliding with axonemal dynein motors, and plays important roles in cell migration and generation of external fluid flow. Since cilia have diverse roles in many tissues and organs in mammal, defects in ciliary activity causes a number of diseases called ciliopathy.

Numerical Modeling of Microvascular Hemodynamics in Plasmodium Falciparum Malaria

High concentrations of nitric oxide (NO) have previously been measured in human maxillary sinuses, but the transport rates between the sinus and the nose during normal breathing have not been quantified. In this study, NO transport has been investigated using published NO concentrations and production rates, computational fluid dynamics (CFD) and first-order modeling in stylised physiological, pathological and post-surgical geometries. The results indicate that physiological sinus geometries cannot supply all the NO found in the nasal cavity. Pathological and post-surgical geometries have higher NO transport and lower steady-state NO concentrations than physiological geometries, but no difference was found between the two surgical techniques considered (inferior and middle meatal antrostomy). All the steady state concentrations are also above the level required for bacteriostatic effects.

Computational biomechanics for investigating various diseases over micro to macro scales

Summary Human cardiovascular system is always under the integrated nervous and humoral control of the whole body, i.e. in homeostasis. Multiple feedback mechanisms with mutual interactions among systems, organs, and even tissues provide integrated control of theentire body. These control mechanisms have different spatial coverages, from the micro- to macroscale, and different time constants, from nanoseconds to decades. We think that these variations in spatial as well as temporal scales should be taken into account in discussing phenomena in the cardiovascular system. In this background, we have been investigating the cardiovascular system over micro to macro levels by using conjugated computational mechanics analyzing fluid, solid and bio-chemical mechanics. In the present study, we introduce our recent researches on a novel hemodynamic index for the initiation of cerebral aneurysms focusing on temporal variation of spatial wall shear stress gradient, the mass transport to saccular aneurysm, and primary thrombus formation. Not only the cardiovascular system, we have also investigated air flow in the lungusingapatientspecificgeometry. Weappliedadaptivemeshrefinement method to efficiently calculate the pulmonary airflow. We introduce these works in this paper, too. In the future analysis, biological phenomena need to be included in discussing physiological as well as pathological, i.e. disease processes. We expect this to be accomplished in the future by integrating new understandings of macroscale and microscale biomechanics, if we continue to be together with advances of related sciences and technologies.

Clinical Education for Engineers: ESTEEM Project

Current engineering applications in the medical arena are extremely progressive. On this occasion, the most frequently encountered and difficult problem must be an insufficient communication between engineers and medical practitioners. The reason is mainly due to the difference of their own cultures. Medical practitioners tend to think about everything based on their experiences episodically. They take it granted that medicine cannot be usually expressed in a strict manner. Another common obstacle is the safety of patients. On the other hand, engineers are usually trained to think about everything based on physical law expressed mathematically. In addition, engineers and medical practitioners cannot always understand one another’s jargon. It is therefore very hard though even not impossible to understand each other without special effort.© 2009 ASME