Cycle Time Variation Research Articles

Variations in growth and cell cycle time of arterial smooth muscle cells cultured at low density.

The population kinetics of cultured rat arterial smooth muscle cells replated at various low densities were studied by direct counting and observation of the cells. Population doubling time decreases with increasing initial density of the culture. These variations in population doubling times depend on both the variation in the percentage of quiescent cells and on the variation of the mean cell cycle time of non-quiescent cells.

CORRELATION BETWEEN CELL SIZE AND POSITION WITHIN THE DIVISION CYCLE IN SUSPENSION CULTURES OF CHANG LIVER CELLS

Chang liver cells from exponentially growing suspension cultures have been separated by sedimentation at unit gravity. Determinations of the protein content per cell showed that the fractionation procedure resulted in good separation of cells of different size. On the other hand, the DNA content of individual cells from the fractions, as determined cytofluorimetrically, indicated considerable heterogeneity in the size of cells from the same stage of the division cycle. On the basis of earlier results on intermitotic growth and the variation in the length of the cell cycle in homogeneous cell populations, a mathematical model has been constructed and tested using a computer program. The present results on the size distribution of cells from the different stages of the mitotic cycle are consistent with a regeneration of size heterogeneity in each cell generation, as a result of the dispersion of intermitotic times. The variation in cell cycle times may be related to a probabilistic event in the G1 period. In the mathematical model it was necessary to include a mechanism by which the regeneration of abnormally large cells is prevented. The experimental data are compatible with a gradually increasing inhibition of growth in cells larger than a certain size (circa 400 pg protein per cell).

Variations in cycle time and certain physiological measures of workers performing a paced assembly task

Continuous monitoring of heart rate, respiration rate and galvanic skin resistance was done for 5 days on five subjects while they assembled drum brake cylinders. Cycle time and number of errors committed (unsuccessful hand movements) were also recorded. The subjects were required to perform the paced, repetitive task over an 8-hour period. Scheduled breaks, similar to local factories, were adhered to. A simple reaction test was given to measure attention. ANOVA on data showed that well rested subjects had higher physiological readings and committed more errors than subjects who had less sleep. An increase in CT and variability seems to be an indication of decrement in work performance and a rest period is needed. An increase in all four parameters is another indicator of poor performance (increase in errors). The simple repetitive task seems to be not motivating enough to keep the worker's attention and keep him aroused enough to work at his peak performance level

Translocation yield from the immature mouse testis and the nature of spermatogonial stem cell heterogeneity

The response of the immature mouse testis to X-irradiation was found to differ from the adult in three respects. 1. (1) Treatment of 5-day old mice with 300 R or 500 R produced no clear sterile period and even with a 1000 R exposure some animals became fertile at maturity. However, others showed a temporary sterile period or were permanently sterilized. 10-day old mice showed a response which more clearly approximated that of the adult. Comparison with histological observations on rats irradiated when immature suggested that the spermatogonia present at this age are not more radioresistant than those of the adult testis but that surviving cells can procede directly into spermatogenesis rather than first repopulating their numbers as in the adult. 2. (2) Testis weights on reaching adulthood were severely reduced and the degree of effect was found to be dependent upon both radiation dose and age at time of treatment. This was attributed largely to the failure of compensatory repopulation in the immature testis but greater cell killing or lower cell numbers in the immature testis could be contributory factors. 3. (3) Translocation yields from mice irradiated at 5 days of age approximated half that of the adult yield with both 300 R and 500 R treatments. This agrees well with Selby's specific locus mutation data from immature mice. Yields from animals exposed to 1000 R at 3 or 5 days of age were extremely low. Translocation yield from these immature mice thus showed a humped dose-response curve as in the adult. The response from 10-day old mice generally approximated that of the adult, this also agreeing with Selby's findings. It is concluded that the low yields are attributable to the presence of proliferating stem cell populations. As in the adult several days after radiation exposure, the stem cells may have a short cell cycle, be sensitive to radiation killing and yield low levels of genetic damage. A model to account for the heterogeneity in radio-sensitive of spermatogonial stem cell populations both in the adult and immature testis is proposed, this based on Smith and Martin's concept of the cell cycle. The heterogeneity is attributed to a variation in cell cycle times within a single stem cell type. Those in a long G 1 (A state) would be the most radioresistant having greater time available for repair of pre-mutational or pre-breakage lesions before the onset of S, those with a shorter A state, leaving the A state, or in other stages of the cell cycle (SG 2M) would be more radiosensitive and contribute most to the total yield of genetic damage at lower (<600 R) X-ray doses. Under normal conditions most cells will be in G 1 and this will account for most of the genetic damage recovered. However, proliferating cells with a much shorter cell cycle must spend a much higher proportion of their time in S and G 2 and the recovery of both translocations and point mutations from these stages should approximate only one-half of that from G 1 due to chromatid segregation. Yields from short cycling cells such as in the immature testis or in the adult following earlier acute (or chronic) radiation exposure will be lower.

Transition probability and the origin of variation in the cell cycle.

IT is well established that the cell cycle times of cells cultured in vitro are highly variable although the origin of this variability has remained unclear1,2. A number of theories have been advanced to explain the variation in cell cycle times although none of them give entirely satisfactory fit to the experimental data2. Any proposal as to the origin of this variability must take account of the observation that most of the variability occurs in the G1 phase of the cell cycle and that it is the length and variability of this phase which is the major determinant of the length and variability of cell cycle times within a cell population1. A new model of the cell cycle has been proposed independently by two groups that suggests that variability in the G1 phase of the cell cycle arises as a result of a probabilistic transition occurring within G1 (refs 3, 4). Using time-lapse cine-photography I have examined the possible role of a number of other factors which might determine this variability and have come to the conclusion that the observed variation in cell cycle times in vitro is qualitatively and quantitatively in accord with variation predicted by the transition probability model of the cell cycle4.

Characterization of the cell cycle of cultured human diploid cells: effects of aging and hydrocortisone.

Age-related changes in the cytokinetics of human diploid cells in vitro have been compared in normal cultures and in cultures in which lifespan has been prolonged by the addition of hydrocortisone to the medium. For both cultures, with advancing age the fraction of cells in the actively proliferating pool decreased and the intercellular variation in cell cycle times increased. The average cell cycle time was prolonged during aging due almost entirely to changes in the duration of G1. The duration of S remained constant, while a small delay in G 2 was observed in late passage cells near the end of their lifespan. Although the same pattern of change in proliferative parameters occurred in both control and hydrocortisone-treated cultures, the changes were somewhat delayed in the presence of the steroid. The results are interpreted in terms of several cell cycle models and suggest that the events controlling cell proliferation are sensitive to hydrocortisone modulation during the G1 and possibly the G2 periods.

Steady State Traffic Optimization by MITROP

MITROP (Mixed-Integer TRaffic Optimization Program) is a new computer program for traffic signal control in urban street networks. It is designed to optimize simultaneously all the traffic control variables of the network including cycle time, splits of green time, and offsets. Both deterministic and stochastic models are used to represent the traffic flow process. The optimization problem is formulated in terms of mixed-integer linear programming and a globally-optimal solution is determined via the MPSX optimization system. The method was applied to several signal-controlled traffic networks, for various demand patterns, and offers certain advantages over existing methods. In particular, it is shown that network performance is sensitive to variations in cycle time, which has to be determined in conjunction with all the other traffic control variables. The paper describes the application of the program to a section of the UTCS/BPS test network in Washington, D.C.

Variation of cell cycle duration within suspension cultures of Daucus carota and its consequence for the induction of ploidy changes with colchicine.

Continuous exposure to colchicine was used to estimate the variation in cell cycle time between cells within suspension cultures ofDaucus carota. Observations were made of the pattern of disappearance of cells of the initially predominant ploidy levels in diploid and tetraploid cultures having markedly different aggregation patterns. Both cultures showed a similar range of cycle times, normally distributed about the culture mean. Shorter colchicine treatments, followed by regrowth in colchicine-free medium, showed that spread of cycle times in the diploid culture prevented uniform induction of tetraploidy, and that the resulting mixoploid suspensions showed a gradual reversion to diploidy during subsequent subculture.

In vitro response of lymphocytes to phytohemagglutinin (PHA) as studied with antiserum to PHA: II. Cell cycle analyses

The cell cycle and phase times of human lymphocytes responding to PHA have been analysed with the percent labelled metaphases (PLM) technique. The range of generation times (13–18 h) and DNA synthesis times (6.5–10.5 h) reported here compare well with previous measurements in the literature. Cycle analyses of the early responding cells of the initial response, selected with partial anti-PHA serum inhibition, and of restimulated cells yield relatively well-defined PLM curves. The short cycle times measured from these curves may reflect the early cycles after stimulation or a subpopulation of responding cells. Analyses at two times during both the initial and restimulation responses suggest that cycles lengthen with time after stimulation. The poor PLM curves of the initial response and the restimulation response of cells released from anti-PHA inhibition indicate considerable intercellular variation in cycle times. Cells in the initial long G 1 phase contribute to this variation. PHA dose does not appear to affect the cycle time.

Variations in crypt cell cycle time and mitotic time in the small intestine of the rat.

A stathmokinetic technique, which has estimable precision, has been used for measuring cell cycle times in rat intestinal epithelial cells. Mitotic times for the epithelial cells have been calculated using cell cycle times together with mitotic indices derived in the absence of a stathmokinetic agent. Both cell cycle and mitotic times in rat intestinal cells showed regional, circadian and age variations, but in animals in which physical activity was increased cell cycle and mitotic times were not appreciably different form those in control rats.

Solar cycle modulation of the radiation belt proton flux

The purpose of this paper is to predict in an exhaustive way the solar cycle time variations to be expected in the trapped radiation belt proton flux on the assumption of a neutron decay source. By ‘exhaustive’ we mean that, once the interested reader decides on suitable models for the earth's atmosphere and magnetic field (we will recommend some), he should, by reading this paper, be able to predict the time variations expected for protons of any energy and pitch angle at any point in space. We have also devoted considerable attention to a derivation from the Boltzmann equation of the simplified proton transport equation commonly used in discussing energetic protons at low L values. Emphasis is given to the various approximations involved.

Changes occurring during the growth of Ehrlich ascites cells in vivo

Kinetic studies of Ehrlich ascites tumour cells 2 and 13 days after transplantation showed that at 13 days mean cell cycle time was increased and there was an extremely long DNA synthetic period (S). Examination of the distribution of label over chromatids at various times after injection of tritiated thymidine ( 3 H-TdR) showed that in the 2 day population there was little variation in cell cycle time but in the 13-day tumour there was a minor fraction of fast cycling cells which had different chromosome number. Distribution of chromosome number in the two populations was the same and so the kinetic changes were not the result of selection of cells of particular ploidy. Microdensitometric measurements of Feulgen stained cells followed by autoradiography to identify cells in S, showed that in the later tumour the decrease in cells in S was accompanied by an increase in cells with G 1 DNA values. Repeated injections of 3 H-TdR to mice with 2-day old tumours labelled all the tumour cells but, when given to mice with 13-day old tumours did not label 20–51% of the tumour cells. Most of the cells which were unlabelled after multiple injections of 3 H-TdR had G 1 DNA contents and their ability to divide quickly once the tumour mass was reduced by transplantation or aspiration was demonstrated. Analysis of the distribution of cell size, using the Coulter counter, showed that as the tumour aged there was an increase in modal cell size and there were more larger cells. This was correlated with an increase in the mean protein content of cells as the tumour aged, as determined by microdensitometric measurements of cells stained with naphthol yellow S. The correlation of individual cell DNA and protein contents suggested a wide range of protein contents for all cells and the possibility of a threshold content which must be reached before DNA synthesis begins is discussed.

The variation of cycle times with repetition for manual tasks.

The variation of cycle time with repetition has engaged the interest of ergonomists, psychologists, statisticians and engineers. The approach most directly useful to industrial management is that which enables time standards to be set more accurately, and which provides a basis for planning and estimating. The original relationships in aircraft manufacture have been found to be very useful for planning and estimating purposes, but are not sufficiently accurate for setting time standards for incentive schemes. It is in this field of time standards that a knowledge of accurate relationships could have a tremendous impact on direct labour costs. Furthermore, it could change fundamentally the existing practices for human work measurement Laboratory experiments to investigate a possible fundamental relationship applicable to all manual operations with varying degrees of skill and cycle time were conducted, Skilled and unskilled subjects performed operations requiring varying degrees of skill and cycle time. In...