The casp9 protein plays a critical role in apoptosis induced by a variety of death stimuli. A regulator of apoptosis, Apaf-1, binds to and activates pro-casp9 in the presence of cytochrome c and dATP, a requirement that is bypassed by deletion of the WD-40 repeats located in the C-terminal half of Apaf-1. In this report, we used constitutively active Apaf-1 mutant lacking the WD-40 repeat region to study the mechanism and regulation of pro-casp9 activation. Mutational analysis revealed that only a small portion of the CED-4 homologous region (residues 456-559) could be deleted without destroying the ability of Apaf-1-(1-559) to activate pro-casp9. Apaf-1 can self-associate to form oligomers. Disruption of Apaf-1 self-association by deletion (Delta109-559) or mutation of the P-loop region (K149R) abrogated Apaf-1-mediated pro-casp9 activation. Forced oligomerization of the caspase recruitment domain of Apaf-1 was sufficient for pro-casp9 activation. Dimerization of chimeric Fpk-pro-casp9 protein with the dimerizer drug FK1012 induced pro-casp9 processing and apoptosis in cells. Significantly, the C-terminal region containing WD-40 repeats interacted with its N-terminal CED-4 homologous region, as determined by immunoprecipitation experiments. Importantly, expression of the WD-40 repeat region inhibited Apaf-1 self-association and proteolytic activation of pro-casp9. These studies provide a mechanism by which Apaf-1 promotes autoactivation of pro-casp9 through Apaf-1 self-association, a process that is negatively regulated by the WD-40 repeats. 相似文献
A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium. 相似文献
The paper proposes a novel metaheuristic based on integrating chaotic maps into a Henry gas solubility optimization algorithm (HGSO). The new algorithm is named chaotic Henry gas solubility optimization (CHGSO). The hybridization is aimed at enhancement of the convergence rate of the original Henry gas solubility optimizer for solving real-life engineering optimization problems. This hybridization provides a problem-independent optimization algorithm. The CHGSO performance is evaluated using various conventional constrained optimization problems, e.g., a welded beam problem and a cantilever beam problem. The performance of the CHGSO is investigated using both the manufacturing and diaphragm spring design problems taken from the automotive industry. The results obtained from using CHGSO for solving the various constrained test problems are compared with a number of established and newly invented metaheuristics, including an artificial bee colony algorithm, an ant colony algorithm, a cuckoo search algorithm, a salp swarm optimization algorithm, a grasshopper optimization algorithm, a mine blast algorithm, an ant lion optimizer, a gravitational search algorithm, a multi-verse optimizer, a Harris hawks optimization algorithm, and the original Henry gas solubility optimization algorithm. The results indicate that with selecting an appropriate chaotic map, the CHGSO is a robust optimization approach for obtaining the optimal variables in mechanical design and manufacturing optimization problems.
Engineering with Computers - In this paper, a Lie-group integrator based on $$GL_4(\mathbb {R})$$ and the reproducing kernel functions has been constructed to investigate the flow characteristics... 相似文献
The Journal of Supercomputing - Left ventricular non-compaction (LVNC) is a rare cardiomyopathy characterized by abnormal trabeculations in the left ventricle cavity. Although traditional computer... 相似文献
In this paper we focus on appearance features particularly the Local Binary Patterns describing the manual component of Sign Language. We compare the performance of these features with geometric moments describing the trajectory and shape of hands. Since the non-manual component is also very important for sign recognition we localize facial landmarks via Active Shape Model combined with Landmark detector that increases the robustness of model fitting. We test the recognition performance of individual features and their combinations on a database consisting of 11 signers and 23 signs with several repetitions. Local Binary Patterns outperform the geometric moments. When the features are combined we achieve a recognition rate up to 99.75% for signer dependent tests and 57.54% for signer independent tests. 相似文献
The aim of the paper is to present a sound, strongly complete and decidable probabilistic temporal logic that can model reasoning about evidence. The formal system developed here is actually a solution of a problem proposed by Halpern and Pucella (J Artif Intell Res 26:1–34, 2006). 相似文献
Optimal synthesis of human movement or the prediction of the kinematics of a new movement require not only that the multi-body system be modeled but also that a performance criterion is specified. For sub-maximal movements the selection of a suitable performance criterion, able to generate realistic dynamic behavior is difficult. A two-dimensional simulation model of the take-off phase of a sub-maximal long jump was developed to study the effect of criterion choice on the realism of simulated movements. A parametric optimization technique was employed to obtain solutions to the constrained equations of motion. Seven different criteria were evaluated, by comparing simulated movements with an actual performance, to identify the criterion which most closely approximated that spontaneously minimized by the athlete. Synthesis of the take-off phase of a sub-maximal long jump was found to be sensitive to the chosen criterion, with a criterion based on minimizing joint intersegmental forces found to perform well. 相似文献
To make media resources a prime citizen on the Web, we have to go beyond simply replicating digital media files. The Web is based on hyperlinks between Web resources, and that includes hyperlinking out of resources (e.g., from a word or an image within a Web page) as well as hyperlinking into resources (e.g., fragment URIs into Web pages). To turn video and audio into hypervideo and hyperaudio, we need to enable hyperlinking into and out of them. The W3C Media Fragments Working Group is taking on the challenge to further embrace W3C??s mission to lead the World Wide Web to its full potential by developing a Media Fragment protocol and guidelines that ensure the long-term growth of the Web. The major contribution of this paper is the introduction of Media Fragments as a media-format independent, standard means of addressing media resources using URIs. Moreover, we explain how the HTTP protocol can be used and extended to serve Media Fragments and what the impact is for current Web-enabled media formats. 相似文献