This article describes and evaluates an approach to create and/or improve tactical agents through direct human interaction in real time through a force-feedback haptic device. This concept takes advantage of a force-feedback joystick to enhance motor skill and decision-making transfer from the human to the agent in real time. Haptic devices have been shown to have high bandwidth and sensitivity. Experiments are described for this new approach, named Instructional Learning. It is used both as a way to build agents from (...) scratch as well as to improve and/or correct agents built through other means. The approach is evaluated through experiments that involve three applications of increasing complexity – chasing a fleer, shepherding a flock of sheep into a pen, and driving a virtual automobile through a simulated road network. The results indicate that in some instances, instructional learning can successfully create agents under some circumstances. However, instructional learning failed to build and/or improve agents in other instances. The Instructional Learning approach, the experiments, and their results are described and extensively discussed. (shrink)

Human diploid fibroblasts have a finite proliferative lifespan in culture, at the end of which they are ararrested with G1 phase DNA contents. Upon serum stimulation, senescent cells are deficient in carrying out a subset of early signal transduction events such as activation of protein kinase C and induction of c‐fos. Later in G1, they uniformly fail to express late G1 genes whose products are required for DNA synthesis, implying that they are unable to pass the R point. Failure to (...) pass the R point may occur because senescent cells are unable to phosphorylate the retinoblastoma protein, owing to the accumulation of inactive complexes of cyclin E/Cdk2 and possibly cyclin D/Cdk4. Senescent cells contain high amounts of p21, a potent cyclin‐dependent kinase inhibitor whose levels are also elevated in cells arrested in G1 following DNA damage, suggesting that both arrests might share a common mechanism. Cell aging is accompanied by a progressive shortening of chromosomal telomeres, which could be perceived by the cells as a form of DNA damage that gives rise to the signals that inactivate the cell cycle machinery. (shrink)

There is now a wealth of information that histone proteins play a primary role in the structural and transcriptional properties of chromatin, the protein‐DNA complex which constitutes the eukaryotic genome1, 2. In light of the crucial role of histones in cellular function, it is not surprising that their structural genes are found to be controlled in conjunction with the cell cycle, with the synthesis of most histones tightly coupled to nuclear DNA replication. The evidence suggests that this linkage between DNA (...) replication and histone synthesis involves the regulated adjustment of histone mRNA levels through both transcriptional and posttranscriptional control process. The possible mechanisms underlying these diverse control processes are described here. (shrink)