Cardiomyocyte transplantation could offer a new approach to replace scarred, nonfunctional myocardium in a diseased heart. Clinical application of this approach would require the ability to generate large numbers of donor cells. The purpose of this study was to develop a scalable, robust, and reproducible process to derive purified cardiomyocytes from genetically engineered embryonic stem (ES) cells. ES cells transfected with a fusion gene consisting of the alpha-cardiac myosin heavy chain (MHC) promoter driving the aminoglycoside phosphotransferase (neomycin resistance) gene were used for cardiomyocyte enrichment. The transfected cells were aggregated into embyroid bodies (EBs), inoculated into stirred suspension cultures, and differentiated for 9 days before selection of cardiomyocytes by the addition of G418 with or without retinoic acid (RA). Throughout the culture period, EB and viable cell numbers were measured. In addition, flow cytometric analysis was performed to monitor sarcomeric myosin (a marker for cardiomyocytes) and Oct-4 (a marker for undifferentiated ES cells) expression. Enrichment of cardiomyocytes was achieved in cultures treated with either G418 and retinoic acid (RA) or with G418 alone. Eighteen days after differentiation, G418-selected flasks treated with RA contained approximately twice as many cells as the nontreated flasks, as well as undetectable levels of Oct-4 expression, suggesting that RA may promote cardiac differentiation and/or survival. Immunohistological and electron microscopic analysis showed that the harvested cardiomyocytes displayed many features characteristic of native cardiomyocytes. Our results demonstrate the feasibility of large-scale production of viable, ES cell-derived cardiomyocytes for tissue engineering and/or implantation, an approach that should be transferable to other ES cell derived lineages, as well as to adult stem cells with in vitro cardiomyogenic activity.

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Stress waves, known as acoustic emissions (AEs), are released by localized inelastic deformation events during the progressive failure of brittle rocks. Although several numerical models have been developed to simulate the deformation and damage processes of rocks, such as non-linear stress-strain behaviour and localization of failure, only a limited number have been capable of providing quantitative information regarding the associated seismicity. Moreover, the majority of these studies have adopted a pseudo-static approach based on elastic strain energy dissipation that completely disregards elastodynamic effects. This paper describes a new AE modelling technique based on the combined finite-discrete element method (FEM/DEM), a numerical tool that simulates material failure by explicitly considering fracture nucleation and propagation in the modelling domain. Given the explicit time integration scheme of the solver, stress wave propagation and the effect of radiated seismic energy can be directly captured. Quasi-dynamic seismic information is extracted from a FEM/DEM model with a newly developed algorithm based on the monitoring of internal variables (e.g. relative displacements and kinetic energy) in proximity to propagating cracks. The AE of a wing crack propagation model based on this algorithm are cross-analysed by traveltime inversion and energy estimation from seismic recordings. Results indicate a good correlation of AE initiation times and locations, and scaling of energies, independently calculated with the two methods. Finally, the modelling technique is validated by simulating a laboratory compression test on a granite sample. The micromechanical parameters of the heterogeneous model are first calibrated to reproduce the macroscopic stress-strain response measured during standard laboratory tests. Subsequently, AE frequency-magnitude statistics, spatial clustering of source locations and the evolution of AE rate are investigated. The distribution of event magnitude tends to decay as power law while the spatial distribution of sources exhibits a fractal character, in agreement with experimental observations. Moreover, the model can capture the decrease of seismic b value associated with the macrorupture of the rock sample and the transition of AE spatial distribution from diffuse, in the pre-peak stage, to strongly localized at the peak and post-peak stages, as reported in a number of published laboratory studies. In future studies, the validated FEM/DEM-AE modelling technique will be used to obtain further insights into the micromechanics of rock failure with potential applications ranging from laboratory-scale microcracking to engineering-scale processes (e.g. excavations within mines, tunnels and caverns, petroleum and geothermal reservoirs) to tectonic earthquakes triggering.

It is found that an ordered and air-stable GaAs͑111͒A-͑1ϫ1͒-Cl surface can be produced by chemical etching/passivation with dilute HCl solution. The synchrotron polarization-dependent Cl K-edge x-ray absorption near-edge structure and x-ray photoelectron spectroscopy studies showed that the surface is terminated with Ga-Cl bonds oriented along the surface normal. Low-energy electron diffraction studies showed a bulklike ͑1ϫ1͒ structure on the Cl-terminated GaAs͑111͒A surface. The Cl termination eliminates surface band-gap states caused by surface oxides. Photoluminescence measurements showed a dramatic increase in the near-band radiative emission rate corresponding to reduction in the occupied surface band-gap states. A reduction of surface gap states by Cl termination was confirmed by surface photovoltage measurements.

Abstract. In this paper, we propose a wave-equation-based travel-time seismic tomography method with a detailed description of its step-by-step process. First, a linear relationship between the travel-time residual t = T obs − T syn and the relative velocity perturbation δc(x)/c(x) connected by a finite-frequency travel-time sensitivity kernel K(x) is theoretically derived using the adjoint method. To accurately calculate the travel-time residual t, two automatic arrivaltime picking techniques including the envelop energy ratio method and the combined ray and cross-correlation method are then developed to compute the arrival times T syn for synthetic seismograms. The arrival times T obs of observed seismograms are usually determined by manual hand picking in real applications. Travel-time sensitivity kernel K(x) is constructed by convolving a forward wavefield u(t, x) with an adjoint wavefield q(t, x). The calculations of synthetic seismograms and sensitivity kernels rely on forward modeling. To make it computationally feasible for tomographic problems involving a large number of seismic records, the forward problem is solved in the two-dimensional (2-D) vertical plane passing through the source and the receiver by a high-order central difference method. The final model is parameterized on 3-D regular grid (inversion) nodes with variable spacings, while model values on each 2-D forward modeling node are linearly interpolated by the values at its eight surrounding 3-D inversion grid nodes. Finally, the tomographic inverse problem is formulated as a regularized optimization problem, which can be iteratively solved by either the LSQR solver or a nonlinear conjugate-gradient method. To provide some insights into future 3-D tomographic inversions, Fréchet kernels for different seismic phases are also demonstrated in this study.