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In treating dynamic systems, sequential Monte Carlo methods use discrete samples to represent a complicated probability distribution and use rejection sampling, importance sampling and weighted resampling to complete the on-linè®ltering' task. We propose a special sequential Monte Carlo method, the mixture Kalman ®lter, which uses a random mixture of the(More)
Flavopiridol is active against chronic lymphocytic leukemia (CLL) cells in vitro and in the treatment of advanced stage disease, but the mechanisms of these actions remain unclear. Originally developed as a general cyclin-dependent kinase inhibitor, flavopiridol is a potent transcriptional suppressor through the inhibition of positive transcription(More)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a wide phenotypic range, often affecting personality and communication. Previous voxel-based morphometry (VBM) studies of ASD have identified both gray- and white-matter volume changes. However, the cerebral cortex is a 2-D sheet with a highly folded and curved geometry, which VBM cannot(More)
Sphingosine-1-phospate (S1P) and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X) receptor agonist) produces modest hypertension in patients (2-3 mmHg in 1-yr trial) as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes(More)
Magnetic resonance (MR) examination provides a powerful tool for investigating brain structural changes in children with autism spectrum disorder (ASD). We review recent advances in the understanding of structural MR correlates of ASD. We summarize findings from studies based on voxel-based morphometry, surface-based morphometry, tensor-based morphometry,(More)
Some tumors are dependent on the continued activity of a single oncogene for maintenance of their malignant phenotype. The best-studied example is the Bcr-Abl fusion protein in chronic myelogenous leukemia (CML). Although the clinical success of the Abl kinase inhibitor imatinib against chronic-phase CML emphasizes the importance of developing therapeutic(More)
Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in chronic lymphocytic leukemia cells by inhibiting Cdk7 and Cdk9, which control transcription. Here we studied the novel Cdk inhibitor SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. We hypothesized that transient inhibition of(More)
PURPOSE SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) 2, 7, and 9, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. A phase I dose-escalation study of SNS-032 was conducted to evaluate safety, pharmacokinetics, biomarkers of mechanism-based pharmacodynamic (PD) activity,(More)
Many researchers have sought to construct diagnostic models to differentiate individuals with very mild dementia (VMD) from healthy elderly people, based on structural magnetic-resonance (MR) images. These models have, for the most part, been based on discriminant analysis or logistic regression, with few reports of alternative approaches. To determine the(More)