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Loss of Bid confers clonogenic survival to granzyme B-treated cells, however the exact role of Bid-induced mitochondrial damage – upstream or downstream of caspases – remains controversial. Here we show that direct cleavage of Bid by granzyme B, but not caspases, was required for granzyme B-induced apoptosis. Release of cytochrome c and SMAC, but not AIF or endonuclease G, occurred in the absence of caspase activity and correlated with the onset of apoptosis and loss of clonogenic potential. Loss of mitochondrial trans-membrane potential (ΔΨm) was also caspase independent, however if caspase activity was blocked the mitochondria regenerated their ΔΨm. Loss of ΔΨm was not required for rapid granzyme B-induced apoptosis and regeneration of ΔΨm following cytochrome c release did not confer clonogenic survival. This functional dissociation of cytochrome c and SMAC release from loss of ΔΨm demonstrates the essential contribution of Bid upstream of caspase activation during granzyme B-induced apoptosis.Cell Death and Differentiation (2006) 13, 607–618. doi:10.1038/sj.cdd.4401772; published online 16 September 2005 [ABSTRACT FROM AUTHOR]

Various microphone array geometries (e.g., linear, circular, square, cubic, spherical, etc.) have been used to improve the positioning accuracy of sound source localization. However, whether these array structures are optimal for various specific localization scenarios is still a subject of debate. This paper addresses a microphone array optimization method for sound source localization based on TDOA (time difference of arrival). The geometric structure of the microphone array is established in parametric form. A triangulation method with TDOA was used to build the spatial sound source location model, which consists of a group of nonlinear multivariate equations. Through reasonable transformation, the nonlinear multivariate equations can be converted to a group of linear equations that can be approximately solved by the weighted least square method. Then, an optimization model based on particle swarm optimization (PSO) algorithm was constructed to optimize the geometric parameters of the microphone array under different localization scenarios combined with the spatial sound source localization model. In the optimization model, a reasonable fitness evaluation function is established which can comprehensively consider the positioning accuracy and robustness of the microphone array. In order to verify the array optimization method, two specific localization scenarios and two array optimization strategies for each localization scenario were constructed. The optimal array structure parameters were obtained through numerical iteration simulation. The localization performance of the optimal array structures obtained by the method proposed in this paper was compared with the optimal structures proposed in the literature as well as with random array structures. The simulation results show that the optimized array structure gave better positioning accuracy and robustness under both specific localization scenarios. The optimization model proposed could solve the problem of array geometric structure design based on TDOA and could achieve the customization of microphone array structures under different specific localization scenarios.