ß-Catenin is required for maintaining hippocampal morphology during the perinatal period.

In mice, the compact hippocampal primordium is formed during the prenatal stage by early-generated neurons that migrate from the lateral ventricular zone. However, despite much being understood about the formation of the hippocampus, the molecular mechanisms that maintain the morphology of the hippocampal primordium after its formation remain to be characterized. ß-Catenin is a key factor of canonical Wnt signaling and also a component of adherens junctions. Previous embryonic deletion studies have demonstrated that ß-catenin is required for early development and generation of granule cells. However, whether ß-catenin is involved in the morphological maintenance of the hippocampus as a cell adhesion molecule is still unknown. Here, we report that perinatal deletion of ß-catenin in postmitotic neurons and some radial glial cells of hippocampus using CamKIIα-iCre; ß-cateninflox/flox conditional knockout mice, leads to disorganization of the radial glial scaffold and consequentially severe defects in hippocampal morphology. We demonstrate that ß-catenin is required for maintaining radial glial scaffold possibly via its well-known role in cell adhesion during the perinatal period. These findings provide essential advances into our understanding of the maintenance of the hippocampal primordium during the perinatal period.

A 3-D elasticity theory based model for acoustic radiation from multilayered anisotropic plates.

A theoretical model built upon three-dimensional elasticity theory is developed to investigate the acoustic radiation from multilayered anisotropic plates subjected to a harmonic point force excitation. Fourier transform technique and stationary phase method are combined to predict the far-field radiated sound pressure of one-side water immersed plate. Compared to equivalent single-layer plate models, the present model based on elasticity theory can differentiate radiated sound pressure between dry-side and wet-side excited cases, as well as discrepancies induced by different layer sequences for multilayered anisotropic plates. These results highlight the superiority of the present theoretical model especially for handling multilayered anisotropic structures.

Engineering three-dimensional cardiac microtissues for potential drug screening applications.

Heart disease is one of the major global health issues. Despite rapid advances in cardiac tissue engineering, limited successful strategies have been achieved to cure cardiovascular diseases. This situation is mainly due to poor understanding of the mechanism of diverse heart diseases and unavailability of effective in vitro heart tissue models for cardiovascular drug screening. With the development of microengineering technologies, three-dimensional (3D) cardiac microtissue (CMT) models, mimicking 3D architectural microenvironment of native heart tissues, have been developed. The engineered 3D CMT models hold greater potential to be used for assessing effective drugs candidates than traditional two-dimensional cardiomyocyte culture models. This review discusses the development of 3D CMT models and highlights their potential applications for high-throughput screening of cardiovascular drug candidates.

Effects of mean flow on transmission loss of orthogonally rib-stiffened aeroelastic plates.

This paper investigates the sound transmission loss (STL) of aeroelastic plates reinforced by two sets of orthogonal rib-stiffeners in the presence of external mean flow. Built upon the periodicity of the structure, a comprehensive theoretical model is developed by considering the convection effect of mean flow. The rib-stiffeners are modeled by employing the Bernoulli-Euler beam theory and the torsional wave equation. While the solution for the transmission loss of the structure based on plate displacement and acoustic pressures is given in the form of space-harmonic series, the corresponding coefficients are obtained from the solution of a system of linear equations derived from the plate-beam coupling vibration governing equation and Helmholtz equation. The model predictions are validated by comparing with existing theoretical and experimental results in the absence of mean flow. A parametric study is subsequently performed to quantify the effects of mean flow as well as structure geometrical parameters upon the transmission loss. It is demonstrated that the transmission loss of periodically rib-stiffened structure is increased significantly with increasing Mach number of mean flow over a wide frequency range. The STL value for the case of sound wave incident downstream is pronouncedly larger than that associated with sound wave incident upstream.

Fluid flow induced calcium response in osteoblasts: mathematical modeling.

Fluid flow in the bone lacuno-canalicular network can induce dynamic fluctuation of intracellular calcium concentration ([Ca(2+)](i)) in osteoblasts, which plays an important role in bone remodeling. There has been limited progress in the mathematical modeling of this process probably due to its complexity, which is controlled by various factors such as Ca(2+) channels and extracellular messengers. In this study we developed a mathematical model to describe [Ca(2+)](i) response induced by fluid shear stress (SS) by integrating the major factors involved and analyzed the effects of different experimental setups (e.g. [Ca(2+)](i) baseline, pretreatment with ATP). In this model we considered the ATP release process and the activities of multiple ion channels and purinergic receptors. The model was further verified quantitatively by comparing the simulation results with experimental data reported in literature. The results showed that: (i) extracellular ATP concentration has more significant effect on [Ca(2+)](i) baseline (73% increase in [Ca(2+)](i) with extracellular ATP concentration varying between 0 and 10 µM), as compared to that induced by SS (25% variation in [Ca(2+)](i) with SS varying from 0 to 3.5 Pa); (ii) Pretreatment with ATP-medium results in different [Ca(2+)](i) response as compared to the control group (ATP-free medium) under SS; (iii) Relative [Ca(2+)](i) fluctuation over baseline is more reliable to show the [Ca(2+)](i) response process than the absolute [Ca(2+)](i) response peak. The developed model may improve the experimental design and facilitate our understanding of the mechanotransduction process in osteoblasts.

Transmission loss of orthogonally rib-stiffened double-panel structures with cavity absorption.

The transmission loss of sound through infinite orthogonally rib-stiffened double-panel structures having cavity-filling fibrous sound absorptive materials is theoretically investigated. The propagation of sound across the fibrous material is characterized using an equivalent fluid model, and the motions of the rib-stiffeners are described by including all possible vibrations, i.e., flexural displacements, bending, and torsional rotations. The effects of fluid-structure coupling are account for by enforcing velocity continuity conditions at fluid-panel interfaces. By taking full advantage of the periodic nature of the double-panel, the space-harmonic approach and virtual work principle are applied to solve the sets of resultant governing equations, which are eventually truncated as a finite system of simultaneous algebraic equations and numerically solved insofar as the solution converges. To validate the proposed model, a comparison between the present model predictions and existing numerical and experimental results for a simplified version of the double-panel structure is carried out, with overall agreement achieved. The model is subsequently employed to explore the influence of the fluid-structure coupling between fluid in the cavity and the two panels on sound transmission across the orthogonally rib-stiffened double-panel structure. Obtained results demonstrate that this fluid-structure coupling affects significantly sound transmission loss (STL) at low frequencies and cannot be ignored when the rib-stiffeners are sparsely distributed. As a highlight of this research, an integrated optimal algorithm toward lightweight, high-stiffness and superior sound insulation capability is proposed, based on which a preliminary optimal design of the double-panel structure is performed.

Direct numerical simulation of single leukocyte deformation in microchannel flow for disease diagnosis.

To better understand the physical mechanism of leukocyte separation via microfluidics, a level set method was employed to analyze the coupled deformation-flow of individual leukocytes in microfluidic parabolic shear blood flow. The results show that: (1) Weber number and viscosity ratio have great effects on the deformation of single leukocyte, (2) difference between the deformation and motion behavior of different subtypes of leukocytes (i.e., granulocytes, lymphocytes, monocytes) was observed, and (3) the existence of a second leukocyte significantly changes the leukocyte deformation and motion. These results shed light on the understanding of the motion and deformation of leukocytes in microchannel flow and provide a theoretical foundation for separating lymphocytes via microfluidics.

Efficiency of infiltration with bupivacain after modified radical mastectomy.

BACKGROUND: Pre-incisional infiltration of anaesthetic is proven to reduce postoperative pain in breast cancer surgery. However, studies of post-incisional infiltration for modified radical mastectomy are rare. The purpose of this study was to investigate whether post-incisional infiltration with bupivacaine provides improved postoperative pain relief and a cost-effective benefit. METHODS: This is a retrospective study. Between January 2006 and May 2008, 139 patients who received modified radical mastectomy were recruited to participate in the study. Patients receiving local infiltration received bupivacaine (0.5% bupivacaine, 5 ml diluted to 10 ml with distilled water) injected into the dermis surrounding the incision after wound suture. Pain intensity was evaluated using a Visual Analogue Scale (VAS) score and measurement of the required doses of meperidine and acetaminophen. The pain score was recorded every eight hours for three days. RESULTS: All patients were female. Seventy-two patients received local infiltration with bupivacaine after wound suture and 67 patients did not. There were no significant differences between the two patient groups in age, body weight and height, length of general anaesthesia and operative time. Hospital stay was significantly shorter for patients receiving local infiltration of bupivacaine. The VAS score was higher up to 16 hours post-surgery for patients who did not receive local infiltration. Meperidine and acetaminophen consumption was less for patients who received local infiltration (P = 0.010). CONCLUSION: Post-incisional wound infiltration with bupivacaine can relieve pain during the first 16 hours after surgery and shorten hospital stay, and it provides a cost-effective benefit.

Analytical modeling of sound transmission across finite aeroelastic panels in convicted fluids.

An analytical approach is formulated to account for the effects of mean flow on sound transmission across a simply supported rectangular aeroelastic panel. The application of the convected wave equation and the displacement continuity condition at the fluid-panel interfaces ensures the exact handling of the complex aeroelastic coupling between panel vibration and fluid disturbances. To explore the mean flow effects on sound transmission, three different cases (i.e., mean flow on incident side only, on radiating side only, and on both sides) are separately considered in terms of refraction angular relations and sound transmission loss (STL) plots. Obtained results show that the influence of the incident side mean flow upon sound penetration is significantly different from that of the transmitted side mean flow. The contour plot of refraction angle versus incident angle for the case when the mean flow is on the transmitted side is just a reverse of that when the mean flow is on the incident side. The aerodynamic damping effects on the transmission of sound are well captured by plotting the STL as a function of frequency for varying Mach numbers. However, as the Mach number is increased, the coincidence dip frequency increases when the flow is on the incident side but remains unchanged when in the flow is on the radiating side. In the most general case when the fluids on both sides of the panel are convecting, the refraction angular relations are significantly different from those when the fluid on one side of the panel is moving and that on the other side is at rest.

Modeling skin thermal pain sensation: Role of non-Fourier thermal behavior in transduction process of nociceptor.

Skin thermal pain is one of the most common phenomena in human daily life (e.g. contact with hot substances) and in clinical thermal therapies (e.g. laser assisted diseased skin ablation), where the thermal behavior in skin tissue is the critical process. However, the underlying physical and neural mechanisms of skin thermal pain are not clearly understood, and there are few attempts to model it. Besides, due to the "lengthy" thermal relaxation time in biological tissue, non-Fourier thermal behavior has been experimentally observed, attracting increasingly attention to this phenomenon. In this paper, a new thermal-neural model was developed in order to investigate the possible role of non-Fourier thermal behavior in the transduction process of skin thermal pain sensation. In the model, the non-Fourier thermal behavior of skin tissue was coupled to the neural response of the nociceptor (special receptor for pain sensation). The results demonstrated that the predicted thermal-neural responses of nociceptors from different bioheat transfer models can deviate substantially under constant surface temperature heating, implying that the non-Fourier thermal feature may play an important role in the nociceptor transduction process of skin thermal pain.

A multi-scale view of skin thermal pain: from nociception to pain sensation.

All biological bodies live in a thermal environment, including the human body, where skin is the interface with a protecting function. When the temperature is out of the normal physiological range, skin fails to protect, and the pain sensation is evoked. Furthermore, in medicine, with advances in laser, microwave and similar technologies, various thermal therapeutic methods have been widely used to cure disease/injury involving skin tissue. However, the corresponding problem of pain relief has limited further application and development of these thermal treatments. Skin thermal pain is induced through both direct (i.e. an increase/decrease in temperature) and indirect (e.g. thermomechanical and thermochemical) ways, and is governed by complicated thermomechanical-chemical-neurophysiological responses. However, a complete understanding of the underlying mechanisms is still far from clear. In this article, starting from an engineering perspective, we aim to recast the biological behaviour of skin in engineering system parlance. Then, by coupling the concepts of engineering with established methods in neuroscience, we attempt to establish multi-scale modelling of skin thermal pain through ion channel to pain sensation. The model takes into account skin morphological plausibility, the thermomechanical response of skin tissue and the biophysical and neurological mechanisms of pain sensation.

Strain rate sensitivity of skin tissue under thermomechanical loading.

There have been limited studies addressing the thermally dependent mechanical properties of skin tissue, although this can contribute to a variety of medical applications. To address this, an experimental study on the tensile behaviour of pig skin tissue under different thermal loading conditions and different mechanical stretching rates was performed. The results indicate that there is a significant variation among skin tensile behaviours under different temperatures and loading rates, which is correlated with dermal collagen denaturation. The Ogden model was used to summarize the effect of the strain rate and the temperature upon the measured constitutive response through two parameters (alpha and mu). These results can be used in future models to improve clinical thermal treatments for skin tissue.

Thermally-induced change in the relaxation behavior of skin tissue.

Skin biothermomechanics is highly interdisciplinary, involving bioheat transfer, burn damage, biomechanics, and physiology. Characterization of the thermomechanical behavior of skin tissue is of great importance and can contribute to a variety of medical applications. However, few quantitative studies have been conducted on the thermally-dependent mechanical properties of skin tissue. The aim of the present study is to experimentally examine the thermally-induced change in the relaxation behavior of skin tissue in both hyperthermal and hypothermic ranges. The results show that temperature has great influence on the stress-relaxation behavior of skin tissue under both hyperthermal and hypothermic temperatures; the quantitative relationship that has been found between temperature and the viscoelastic parameter (the elastic fraction or fractional energy dissipation) was temperature dependent, with greatest dissipation at high temperature levels.

Analytical and experimental investigation on transmission loss of clamped double panels: implication of boundary effects.

The air-borne sound insulation performance of a rectangular double-panel partition clamp mounted on an infinite acoustic rigid baffle is investigated both analytically and experimentally and compared with that of a simply supported one. With the clamped (or simply supported) boundary accounted for by using the method of modal function, a double series solution for the sound transmission loss (STL) of the structure is obtained by employing the weighted residual (Galerkin) method. Experimental measurements with Al double-panel partitions having air cavity are subsequently carried out to validate the theoretical model for both types of the boundary condition, and good overall agreement is achieved. A consistency check of the two different models (based separately on clamped modal function and simply supported modal function) is performed by extending the panel dimensions to infinite where no boundaries exist. The significant discrepancies between the two different boundary conditions are demonstrated in terms of the STL versus frequency plots as well as the panel deflection mode shapes.

Modeling of nociceptor transduction in skin thermal pain sensation.

All biological bodies live in a thermal environment with the human body as no exception, where skin is the interface with protecting function. When the temperature moves out of normal physiological range, skin fails to protect and pain sensation is evocated. Skin thermal pain is one of the most common problems for humans in everyday life as well as in thermal therapeutic treatments. Nocicetors (special receptor for pain) in skin play an important role in this process, converting the energy from external noxious thermal stimulus into electrical energy via nerve impulses. However, the underlying mechanisms of nociceptors are poorly understood and there have been limited efforts to model the transduction process. In this paper, a model of nociceptor transduction in skin thermal pain is developed in order to build direct relationship between stimuli and neural response, which incorporates a skin thermomechanical model for the calculation of temperature, damage and thermal stress at the location of nociceptor and a revised Hodgkin-Huxley form model for frequency modulation. The model qualitatively reproduces measured relationship between spike rate and temperature. With the addition of chemical and mechanical components, the model can reproduce the continuing perception of pain after temperature has returned to normal. The model can also predict differences in nociceptor activity as a function of nociceptor depth in skin tissue.

Skin biothermomechanics for medical treatments.

Electromagnetic heating, such as microwave, radiofrequency, and laser etc., is widely used in medical treatments. Recent advances in these technologies resulted in remarkable developments of thermal treatments for a multitude of diseases and injuries involving skin tissue. The comprehension of heat transfer and related thermomechanics in skin tissue during these treatments is thus of great importance, and can contribute to the further developments of these medical applications. Biothermomechanics of skin is highly interdisciplinary, involving bioheat transfer, burn damage, biomechanics, and physiology. The aim of this study is to develop a computational approach to examine the heat transfer process, heat-induced mechanical response, as well as the associated pain level, so that the differences among the clinically applied heating modalities can be quantified. In this paper, numerical simulation with the finite difference method (FDM) was used to analyze the temperature, burn damage, and thermal stress distributions in the skin tissue subjected to various thermal treatments. The results showed that the thermomechanical behavior of skin tissue is very complex: blood perfusion has little effect on thermal damage, but a large influence on skin temperature distribution, which, in turn, influences significantly the resulting thermal stress field; for laser heating, the peak temperature is higher for lasers with shorter wavelengths, but the peak is closer to the skin surface; the thermal stress due to laser and microwave heating is mainly limited to the top epidermis layer due to the exponential decrease of heat generation along skin depth; the thin (and commonly overlooked) stratum corneum layer dominates the thermomechanical response of skin tissue.

Vibroacoustic behavior of clamp mounted double-panel partition with enclosure air cavity.

A theoretical study on the vibroacoustic performance of a rectangular double-panel partition clamp mounted in an infinite acoustic rigid baffle is presented. With the clamped boundary condition taken into account by the method of modal function, a double Fourier series solution to the dynamic response of the structure is obtained by employing the weighted residual method (i.e., the Galerkin method). The double series solution can be considered as the exact solution of the problem, as the structural and acoustic-structural coupling effects are fully accounted for and the solution converges numerically. The accuracy of the theoretical predictions is checked against existing experimental data, with good agreement achieved. The influence of several key parameters on the sound isolation capability of the double-panel configuration is then systematically studied, including panel dimensions, thickness of air cavity, elevation angle, and azimuth angle of incidence sound. The present method is suitable for double-panel systems of finite or infinite extent and is applicable for both low- and high-frequency ranges. With these merits, the proposed method compares favorably with a number of other approaches, e.g., finite element method, boundary element method, and statistical energy analysis method.

Sound absorption of cellular metals with semiopen cells.

A combined experimental and theoretical study is presented for the feasibility of using aluminum foams with semiopen cells for sound-absorption applications. The foams are processed via negative-pressure infiltration, using a preform consisting of water-soluble spherical particles. An analytical model is developed to quantify the dependence of pore connectivity on processing parameters, including infiltration pressure, particle size, wetting angle, and surface tension of molten alloy. Normal sound-absorption coefficient and static flow resistance are measured for samples having different porosity, pore size, and pore opening. A theory is developed for idealized semiopen metallic foams, with a regular hexagonal hollow prism having one circular aperture on each of its eight surfaces as the unit cell. The theory is built upon the acoustic impedance of the circular apertures (orifices) and cylindrical cavities due to viscous effects, and the principle of electroacoustic analogy. The predicted sound-absorption coefficients are compared with those measured. To help select processing parameters for producing semiopen metallic foams with desirable sound-absorbing properties, emphasis is placed on revealing the correlation between sound absorption and morphological parameters such as pore size, pore opening, and porosity.

Tyrosine kinase expression profile in bladder cancer.

The expression pattern of tyrosine kinase in bladder cancer cells was evaluated by PCR amplification with degenerate primers derived from conserved catalytic domain in tyrosine kinase. The results indicated that TRK-E and Arg kinases were more abundantly expressed than several other kinases in bladder cancer. In addition, we identified a novel clone whose sequence could not be matched in GeneBank. This clone may represent a serine/threonine kinase based on sequence similarity.