Semi-sinusoidal pattern

The case of the continuous infusion of 5-FU is considered in Fig. 10.5e. Because the total amount of 5-FU administered over 24 h is the same as for the circadian semi-sinusoidal patterns, the level of 5-FU - and hence the cytotoxic effect of the drug - is sometimes below and sometimes above that reached with the circadian schedule. The numerical simulations of the automaton model indicate that the cytoxicity is comparable to that observed for the most toxic circadian pattern, with peak delivery of 5-FU at 4 p.m. 

In a previous study [33] we described the rise in Weel and Cdkl by a step increase lasting 4 h. Here, instead of such a square-wave pattern, we will use a temporal pattern of semi-sinusoidal shape. Thus, we assume that Weel increases in a semi-sinusoidal manner between 4 p.m. and 4 a.m., with a peak at 10 p.m., while Cdkl increases in the same manner between 10 p.m. and 10 a.m., with a peak at 4 a.m. (Fig. 10.3a). 

In simulating the cell cycle automaton response to 5-FU, we impose a circadian profile of the anticancer medication similar to that used in clinical oncology [30, 31] 5-FU is delivered in a semi-sinusoidal manner from 10p.m. to 10a.m., with a peak at 4 a.m. (Fig. 10.3b). During the remaining hours of the day and night, the drug concentration is set to zero. For comparison, we consider similar drug delivery patterns shifted in time, with peak delivery either at 10 a.m., 4 p.m., or 10 p.m. 

It is useful to compare the circadian patterns of 5-FU delivery with the more conventional constant infusion drug-delivery pattern, in which the amount of 5-FU delivered over the 24-h period is the same as for the circadian delivery schedules. The quantity of 5-FU (Qsfu) delivered over 24 h according to the semi-sinusoidal schedule defined by Eq. (3) is given by Eq. (5) ... 

Figure 4.19 shows a schematic representation of state-of-the-art expression apparatus. The more conventional piston press apparatus described in Section 4.5.1 is augmented with the addition of a computer driven pressure regulator which allows the pressure applied to the piston to be carefully controlled and varied according to a preset pattern (e.g. ramp, sinusoidal etc.). The interfaced rotary or linear encoder, force transducer and electronic balance allow semi-continuous measurements of piston displacement, transmitted pressure and... 

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