Flip-flops

In all ealculations done so far a fixed stepsize r = 0.1 has been used. Hence an application of formula (9) leads to the following table concerning flip- flop probabiliti< s Ix tween different conformations. 

The account begins with binary arithmetic, moves on to on-off (flip-flop) electronic switches, then to serial and parallel processing, and finally to computers/transputers. 

There is an electronic circuit called a flip-flop. It consists of two transistors connected in such a way that, if a voltage is applied, one side of the circuit becomes active and the other side not if a second voltage is applied, the circuit flips so that the active side becomes inactive and vice versa. Thus, just as with a conventional switch for which one touch puts it on and a second touch turns it off, one touch of the flip-flop turns it on and a second touch turns it ojf. Addition of two binary numbers now becomes possible. Suppose we want to add 2 -(- 1 (= 3 decimal). First, the numbers must be converted into binary code (10 and 01) and these become switch settings in the machine, but we need four switches so that 10 becomes on, off and 01 becomes off, on (Figure 42.6). 

If the first pair of switches is examined, one is off and the other on, and the result of touching each must be a resulting on (off-on and on-off, giving a total of on). For the other pair, exactly the opposite sequence is present but the net result is on. As far as the machine is concerned, the result is on, on, which in binary code is 11 and in decimal code is 3, the correct answer. Therefore, to get the machine to add in binary, it is necessary to have a switch for each power of two that we want. The number 2 is 64 (decimal) and, to represent any number up to 63, we must have seven switches (seven flip-flop circuits), viz., 2, 2, 2, 2, 2 , and zero. In computer jargon, these... 

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

The MC34067 has only a simple eomparator with a 1.0 V threshold that then latehes an R-S flip-flop. Either the input voltage must be removed and then reapplied, or the Vee of the eontrol IC must be interrupted momentarily to reset the failure lateh. 

Technical term for properties of electrical or neural circuits (flip-flop switch) to rest in two distinct states while avoiding intermediate states (e.g., behavioral state sleep-wake transitions). 

The elimination half-life after oral dosing is longer than after intravenous dosing (TU2po > TU2iv) when the so-called flip-flop condition applies (Ka < Ke). 

There is nothing in Equations 1-8 which is an all-or-none situation. There are no positive feedback loops which might cause some kind of flip-flop of states of operation of the system. There are some possibilities for saturation phenomena but all relationships are graded. Overall, transient or steady-state, the changes of concentration of P-myosin are continuous, monotonic functions of the intracellular Ca ion concentration. On this basis it is more appropriate to say that smooth muscle contraction is modulated rather than triggered by Ca ion. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

Since the contributions of the three constiments of the van der Waals attraction are additive, one can consider each contribution separately. This indeed proves to be convenient not only because all the contributions exhibit distinct scaling with the parameters, but each contribution comes to dominate the expansivity at somewhat distinct temperatures. We consider first the ripplon-ripplon attraction. This contribution appears to dominate the most studied region around 1 K. The off-diagonal (flip-flop) interaction between the ripplons has the form... 

Lipophilicity is intuitively felt to be a key parameter in predicting and interpreting permeability and thus the number of types of lipophilicity systems under study has grown enormously over the years to increase the chances of finding good mimics of biomembrane models. However, the relationship between lipophilicity descriptors and the membrane permeation process is not clear. Membrane permeation is due to two main components the partition rate constant between the lipid leaflet and the aqueous environment and the flip-flop rate constant between the two lipid leaflets in the bilayer [13]. Since the flip-flop is supposed to be rate limiting in the permeation process, permeation is determined by the partition coefficient between the lipid and the aqueous phase (which can easily be determined by log D) and the flip-flop rate constant, which may or may not depend on lipophilicity and if it does so depend, on which lipophilicity scale should it be based ... 

Colin, H., Hilaireau, P., and Martin, M., Flip-flop elution concept in preparative liquid chromatography, /. Chromatogr., 557, 137, 1991. 

Regev, R. Eytan, G. D., Flip-flop of doxorubicin across erythrocyte and lipid membranes, Biochem. Pharmacol. 54, 1151-1158 (1997). 

Phospholipids, which are one of the main structural components of the membrane, are present primarily as bilayers, as shown by molecular spectroscopy, electron microscopy and membrane transport studies (see Section 6.4.4). Phospholipid mobility in the membrane is limited. Rotational and vibrational motion is very rapid (the amplitude of the vibration of the alkyl chains increases with increasing distance from the polar head). Lateral diffusion is also fast (in the direction parallel to the membrane surface). In contrast, transport of the phospholipid from one side of the membrane to the other (flip-flop) is very slow. These properties are typical for the liquid-crystal type of membranes, characterized chiefly by ordering along a single coordinate. When decreasing the temperature (passing the transition or Kraft point, characteristic for various phospholipids), the liquid-crystalline bilayer is converted into the crystalline (gel) structure, where movement in the plane is impossible. 

Another A-to-G editing, at a site designated the R/G site, can occur immediately preceding the flip-flop segment in GluR2-GluR4. The flip-flop segment influences the rate of desensitization, while the rate of recovery from the desensitized state depends on the R/G site where the edited form, G, recovers faster than the unedited form, R. 

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

The flip-flop switch controlling wake-sleep transitions... 

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