External Control Mechanisms

Cell division activities are controlled to a high degree by externally determined growth conditions such as nutrient supply. A cell may stop cell division if the physiological conditions are unfavorable. 

Mitogenic Signals during Cell-cell Conununication 

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An oscillating system is formed by the interplay of the three protein classes and the activity of this system makes up the specific biochemical functions of the individual phases of the cycle. The activity of the cychn-dependent protein kinases (CDKs) is central to the oscillating system. These create a signal that initiates downstream biochemical processes and thus determines the individual phases of the cycle. CDK activity is also the starting point for intrinsic and external control mechanisms. 

Another category could be a hybrid of internal and external control mechanisms. 

External Control. The use of external control to govern the release of dmgs from dehvery systems has largely been experimental. A number of mechanisms have been explored, and include external sources such as electrical currents, magnetism, ultrasound, temperature changes, and irradiation. 

It is the basic task of electrochemical kinetics to establish the functional relations between the rate of an electrochemical reaction at a given electrode and the various external control parameters the electrode potential, the reactant concentrations, the temperature, and so on. From an analysis of these relations, certain conclusions are drawn as to the reaction mechanism prevailing at a given electrode (the reaction pathway and the nature of the slow step). 

We now introduce the concept of the control parameter X (see Section III. A). In the present scheme the discrete time sequence Xk Q transition probability Wt(C C) now depends explicitly on time through the value of an external time-dependent parameter X. The parameter Xk may indicate any sort of externally controlled variable that determines the state of the system, for instance, the value of the external magnetic field applied on a magnetic system, the value of the mechanical force applied to the ends of a molecule, the position of a piston containing a gas, or the concentrations of ATP and ADP in a molecular reaction coupled to hydrolysis (see Fig. 3). The time variation of the control parameter, X = - Xk)/At, is... 

Single molecule pulUng experiments can be described with the formalism developed in Section lll.C.l. In the simplest setting the configurational variable C corresponds to the molecular extension of the complex (handles plus inserted molecule) and the control parameter X is either the force/measured in the bead or the molecular extension of the system, x. For small enough systems the thermodynamic equation of state is dependent on what is the variable that is externally controlled [87]. In the actual experiments, the assumption that either the force or the extension is controlled is just an approximation. Neither the molecular extension nor the force can be really controlled in optical tweezers [88]. For example, in order to control the force a feedback mechanism must operate at aU times. This feedback mechanism has a time delay response so the force is never really constant [89, 90]. By assuming that the force is constant. 

Fig. 13.3. Control points of the cell cycle external and internal control mechanisms. Important control points of the cell cycle lie at the end of G2 phase (G2/M transition), in mitosis (metaphase/anaphase transition) and in Gi phase (restriction point). The internal controls are shown as broken arrows and the external controls are shown as solid arrows.

In addition to the built-in protection and control mechanisms, the cell is also subject to a number of external controls, which ensure that cell division occurs in balance with the overall development of the organism and with external growth conditions. This is a kind of social control of cell division that regulates the progress of the cell cycle, with the help of circulating signal molecules or via cell-cell interactions. 

When mitosis has been completed, the cell requires signals in the form of growth factors to direct towards a new roimd of division. The signals become effective in the first two-thirds of Gi phase. In this time window, the cell is programmed to begin a new cell cycle or to enter Go phase. After a particular point, the restriction point R, no further signals are needed to continue the cell cycle. The cell cycle apparatus is self-contained from this point onwards. S, G2 and M phase occur without external control. The cell cycle may still be halted after crossing the restriction point, however, if the cell detects, via internal control mechanisms or checkpoints, that defects have occurred in the correct course of the phases. 

Furthermore, eq. (5.233) is valid for a reaction-limited system, i.e. the controlling mechanism is the reaction step. Furthermore, the effectiveness factor is unity. The situation becomes more complex in the case where internal and external resistances exist as the effectiveness factor and the mass transfer coefficient should be taken into account (see eq. (5.211)) and they are a function of temperature. 

The unzipping procedure reveals the diagnostically significant trends in fractionation widths and patterns illustrated by Figure 3. These trends can lead to qualitative insights into IVR mechanisms and can suggest optimal schemes for external control over intramolecular dynamics. The unzipped polyads can also yield quantitative least-squares refinements of anharmonic coupling constants, from which any dynamical quantity based on (Q, 0 may be calculated. 

In the model developed by Thomas [J. Am. Chem. Soc. 66, 1664 (1944)], the controlling mechanism is the surface kinetics represented by the Langmuir isotherm. Extensions of this work by Vermeulen et al. (1984) incorporate external surface and pore diffusional resistances. 

The existence of two stable steady states for the same values of the externally controlled constraints is known as bistability . A mechanical analogy to such a situation is the double well potential shown in Fig. 2. (No potential function is known to exist for open chemical systems that would play the role of the gravitational potential energy in... 

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