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Many organisms display rhythms of physiology and behavior that are entrained to the 24-h cycle of light and darkness prevailing on Earth. Under constant conditions of illumination and temperature, these internal biological rhythms persist with a period close to 1 day ("circadian"), but it is usually not exactly 24h. Recent discoveries have uncovered(More)
Progress of a cell through its reproductive cycle of DNA synthesis and division is governed by a complex network of biochemical reactions controlling the activities of both M-phase- and S-phase-promoting factors. Standard chemical kinetic theory provides a disciplined method for expressing the molecular biologists' diagrams and intuition in precise(More)
The activation of maturation promoting factor (MPF, cyclin B/Cdc2), which starts mitosis, is modeled as a bistable biochemical switch or trigger. A small, slow parameter change can cause an abrupt transition by a saddle-node bifurcation from a stable steady state of low activity to one of high activity. The switch is not reversed if the parameter change is(More)
Some of the events of the cell cycle appear to be triggered by a bistable mechanism. A bistable biochemical system can respond to a small, slow signal and is carried by positive feedback from one stable steady state directly to another, in an all-or-none manner. Slow or subthreshold stimuli do not cause accommodation or loss of excitability. Switching is(More)
The usefulness of a short-term azaserine [CAS: 115-02-6; diazoacetate serine (ester)]-rat model for the screening of retinoids (known chemopreventive agents) and the effect of two retinoids on the growth of azaserine-induced, presumptive preneoplastic foci of acinar cells were examined. At 14 days of age, male Lewis rats were each given injections of a(More)
In mammalian cells, the heterodimeric kinase cyclin E/CDK2 (EK2) mediates cell cycle progress from G1 phase into S phase. The protein p27Kip1 (p27) binds to and inhibits EK2; but EK2 can phosphorylate p27, and that leads to the deactivation of p27, presumably liberating more EK2 and forming a positive-feedback loop. It has been proposed that this(More)