Continuous synchrony

Mitsui, A., Cao, S., Takahashi, A., and Arai, T. (1987). Growth synchrony and cellular parameters of the unicellular nitrogen-fixing marine cyanobacterium Synechococcus sp. strain Miami BG 043511 under continuous illumination. Physiol. Plantarum. 64, 1—8. 

To overcome these limitations imposed on conventional and microfluidic methods for size separation, hydrophoretic methods have been developed. Here we provide a review of the methods for continuous size separation of microparticles, blood cells and cell-cycle synchrony, and for sheathless focusing of cells without external fields and sheath flows in microfluidic devices. We describe details of the separation mechanism and its application to particle and cell manipulation, comparing its advantages and disadvantages with other microfluidic methods. Finally, we present some challenges of the hydrophoretic technology. 

Chaotic systems. Here the mere notion of synchrony is non-trivial, and several concepts have been developed. The effect of phase synchronization is a direct extension of the classical theory to the case of a subclass of self-sustained continuous time chaotic oscillators which admit a description in terms of phase. Synchronization of these systems can be described as a phase and frequency locking, in analogy to the theory of synchronization of noisy systems. An alternative approach considers a synchronization of arbitrary chaotic systems as a coincidence of their state variables (complete synchronization) or as an onset of a functional relationship between state variables of two unidirection-ally coupled systems (generalized synchronization). Although physical mechanisms behind the two latter phenomena essentially differ from the mechanisms of phase and frequency locking, all these effects constitute the field of application of the modern synchronization theory. 

When heterokaryons are formed between animal cells the nuclei in the same cytoplasm undergo synchronous initiation of DNA synthesis (Harris and Watkins, 1965) similar synchrony is observed in binucleate cells occurring in mouse embryo cultures (Church, 1967). DNA synthesis has been examined in multinucleate HeLa cells formed by fusion between cells in different phases of the life cycle (Rao and Johnson, 1970). There was a rapid induction of DNA synthesis in G1 phase nuclei following the fusion of G1 and S phase cells. When S phase cells were fused with G2 phase cells, no induction of DNA synthesis was observed in G2 phase nuclei and, no matter what the ratio of G2 S nuclei in the fused cell, the S phase nuclei continued DNA synthesis. 

In this section we shall look for evidence that imperfections in the synchrony, first of division then of DNA replication, reflect the fact that, in this system, cells can engage in DNA replication beyond a critical time limit antecedent to the time when most cells show synchronous division. In a preceding section it was reported that asynchronous entry of the cells into DNA replication continued for 40 or so minutes after the end of heat shocks. Also, evidence was presented that there is a time point 35 or so minutes before the shocks are ended, after which no cell that takes part in synchronous division at its peak can have entered into DNA synthesis. What is then the contribution to synchronous division of the fraction of cells that in fact enter DNA synthesis in the critical 1.25-hour interval between the two indicated times These cells will not have had time to finish S and normal G2 before they are supposed to participate in the first synchronous division. We shall see that in fact they contribute negatively to the synchrony, either by dividing later than at the time when synchronous division is at its peak or by not dividing at all. 

This report has indicated that truly synchronous cell division is limited to the major fraction of cells that initiates replication prior to a time point midway between the two last heat shocks. At this time the population lacks the information that the heat treatment will be discontinued after the next heat shock, and cells continue to engage asynchronously in DNA synthesis. Experiments indicate that this occurs until around the time (EH + 40 minutes) when the next heat shock would have occurred. We have argued that cells that replicate late in the program of heat shocks perturb the division synchrony and subsequently perturb the DNA replication synchrony. It is therefore suggested that further work on temperature synchronization of Tetrahymem cell division should be directed toward the goal of preventing new engagement in DNA replication after a critical time in advance of the synchronous division. 

One observation of interest has been made and is illustrated in Figure 22. The question is what happens if we synchronize repetitively, using four shocks spaced 150 minutes apart, and then shift to the multiple heat shock procedure. We know by now that the first four shocks can start a train of synchronous, free-running cell divisions, each closely followed by synchronous DNA replication. However, when the shift is made as described to the multiple shock procedure, divisions are suppressed but DNA replication continues as a cyclic, though damped, phenomenon occurring with a period of nearly four hours (lower curve, main culture). Samples were removed at the end of each new heat shock. They displayed synchronous division after 1.5 hours at 28 C. The quality of this synchrony (upper curves) bears a distinct relationship to the phase in the DNA replication cycle at the time the sample was removed from the main culture. 

Fig. 21. Free-running synchrony by four heat shocks (upper continuous curve) and restricted repetitive synchrony by four to five heat shocks (upper continuous curve extended by dashed curve). Results of electronic cell counts and of chemical analyses refer to the restricted system at the end of shock 5 (7.2 x 10 cells/ml) DNA 12.5 RNA 344 protein 3,330 ju/ig/cell. Tetrahymena cells synchronized repetitively and under restricted conditions are of almost the same size as are normally growing cells. This will be apparent from comparison of the figures just presented with those in the legend accompanying Figure 11 in the review by Zeuthen Rasmussen, 1971.

Two general classes of methods exist for attaining synchrony in batch and/or continuous culture ... 

Synchronous culture a synchronized cell population, in which all cells divide and pass through subsequent phases of the cell cycle at Ae same time. Synchronization can be achieved in various ways, e.g. by nutrient limitation, light stimulation, temperature change, treatmennt with antimetabolites of nucleic acid metabolism. In S.c. the cell count increases stepwise. Synchrony is usually lost after a few synchronous divisions, i.e. the cell count reverts to a continual increase. S.c. techniques have been applied to various bacteria, Chlorella, Euglena gracilis, etc. Light... 

The fed-batch technique of cultivation is limited by fermenter volume because the volume of fermentation broth increases after each substrate addition. This disadvantage can be avoided by application a cyclic feeding strategy [9-11] which allows one to control the synchrony of individual cell development [9] by the limiting substrate concentration. The preliminary simulation results on a computer show that this type of environmental control of continuous production of exocellular hydrolytic enzymes based on our model is very promising. 

In Figure 7.14, again 3 denotes the compression fingers made with IPMNCs, 5 is the heart itself, 4 depicts an encapsulated enclosure filled with water to create a soft cushion for the compression fingers, 4d s are IPMNC based sensors cilia to continuously monitor the compression forces applied to the heart and 3e and 3f are the associated wiring and electronics. Note that, assisting or soft compression of the left ventricle of a weak heart will produce more internal pressure to pump more blood in synchrony with the natural systolic contraction of the ventricle. Additionally, the proposed system will also provide... 

Tinnitus is a subjective experience characterized by a ringing, buzzing, roaring, whistling, or hissing sound in the ear. The perception ofthe noise occurs without an acoustic stimulus. The noise may occur intermittently, continuously, or in synchrony with the heartbeats. Hearing loss is usually present with this disorder. Almost all disorders ofthe ear may be associated with tinnitus. 

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