Cycle Time Estimation Research Articles

Development of a real time visualization system for the shape of a tokamak plasma cross section

A real time visualization system for the shape of a tokamak plasma cross section has been developed by using Versa Module Europebus (VME)-standardized modules. Digital signal processors (DSPs) are used in parallel for magnetic analysis. A fast and high resolution graphics control processor is adopted for part of the display system. Fast shape identification methods are presented in which tabulated Green’s functions are utilized. The analysis errors are evaluated with Hitachi tokamak 2 (HT-2) experimental data. The plasma shape is visualized in real time with the cycle time of 30 ms. When this system is applied to the International Thermonuclear Experimental Reactor (ITER), the estimated cycle time for visualizing the plasma shape is 40 ms.

Mechanistic Design of Conventional Plunger-Lift Installation

ABSTRACT A mechanistic model for conventional plunger lift installation design is presented. This model applies to oil wells with high gas-liquid ratios and is based on the fundamental equations of momentum balance and mass conservation. The model considers that the rate of liquid fall-back produced when the plunger rises is a linear function of the average rise velocity. The obtained set of ordinary non-linear differential equations needs to be solved numerically. A Fortran computer program for both personal and mainframe based computers was implemented. This permits the calculation of fall-back losses and allows the estimation of optimum cycle time. The model, verified with field quality data, has been shown to represent observed production trends in the wells studied, in particular the shape of the fall-back versus driving pressure ratio on the plunger is reproduced correctly. Differences between liquid/gas production and model estimations fall in the 15 to 20 percent range. This result is encouraging, considering the difficulty involved in obtaining accurate field measurements. The computer program developed can be effectively used for the design and troubleshooting of conventional plunger lift installations.

A New Method to Evaluate Thin Film Adhesion

Abstract This paper discusses a new method of evaluating thin film adhesion both qualitatively and quantitatively via a combination of peeling and image processing techniques. The adhesion of thin film on the entire substrate can be quickly evaluated and quantified to a continuous response variable which is superior to a discrete response variable as described in the ASTM D3359-78 publication. Feasibility of this technique has been demonstrated through a gauge capability study which resulted in 2.7% P/T (precision to tolerance) ratio at six sigma standard deviation for a tolerance of 100. Experimental results using the proposed method to evaluate the process/property relationship of aluminum films as deposited onto various dielectric substrates such as polyimide, silicon dioxide, and silicon nitride have been obtained and have been shown to agree with conventional stud pull test results. The estimated cycle time to evaluate thin film adhesion is five minutes per 4-inch size wafer once the sample is prepar...

Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine.

Postnatal bone growth occurs by the process of endochondral ossification in cartilaginous growth plates at the ends of long bones. The rate and extent of long bone growth is determined by a combination of chondrocytic proliferation, matrix production, and increase in chondrocytic height in the direction of growth during cellular enlargement. In this study, single pulse and/or repeated pulse labeling with the thymidine analog bromodeoxyuridine (BrdU) was used to study the role of cellular proliferation in controlling long bone growth. Variables studied included progression of the label over time following a pulse, and patterns and progression of the label over time following repeated pulse labeling for 24 and 48 hours. Examination was made of the proliferative characteristics of chondrocytes, the spatial pattern of cellular proliferation, and cell cycle kinetics. With respect to the spatial pattern of proliferative chondrocytes, results suggest that chondrocytes within a column are more synchronized with each other than are chondrocytes in different columns. This is consistent with the concept that each column represents a clonal expansion of a stem cell, which may proceed independently from adjacent columns. Despite this apparent heterogeneity, all chondrocytes in the proliferative zone complete at least one cell cycle in 24-28 hours. This estimate of the cell cycle time is significantly shorter than previous estimates of cell cycle times in similar growth plates. Our results also suggest that chondrocytes entering the cell cycle in the proximal part of the growth plate spend an average of 4 days in the proliferative cell zone, representing approximately four cellular divisions. After leaving the cell cycle, an additional 48 hours is required for the label to reach the terminal chondrocyte, which represents the time required to complete hypertrophy. These data are important when considering hypotheses concerning both the role of controls on proliferation in the determination of overall rate of long bone growth, as well as the interplay between proliferation and hypertrophy in regulating the overall amount of growth achieved by a given growth plate.

Estimating cycle time in design for robotic assembly

Estimating cycle time in design for robotic assembly

A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction

The relationship between immunoreactivity for cell proliferation markers (Ki67 and PCNA) and the growth fraction as determined by the fraction of labelled mitoses method was assessed in xenograft tumours grown from the LoVo cell line in nude mice. FLM curves were constructed by injecting tritiated thymidine and then preparing autoradiographs from the tumours. From this data an estimate of growth fraction and cell cycle time were made. Using frozen material from the same tumours, the Ki67 index was determined by immunostaining. PCNA staining was determined in the fixed material which had been used for the autoradiographs. The results show that Ki67 staining follows the same trend as the FLM-determined growth fraction as the tumour increases in size and the rate of growth decreases. However the Ki67 index does produce a consistent overestimate of the growth fraction in this in-vivo system, as compared to observations in cell culture. PCNA staining showed virtually 100 per cent positive staining in all the tumours, which is likely to reflect the long half-life of the antigen, compared to the very fast cell-cycle time of the xenograft tumours. These results show that staining with proliferation markers is not a precise determinant of growth fraction. Ki67 staining is a method that can be usefully applied as an operational marker of cell proliferation, but should not be used uncritically. Further caution is necessary in the use of PCNA. The findings also demonstrate the need to use a range of methods when assessing a new proliferation marker.

Estimating cycle time in design for robotic assembly

Abstract The Design for Robotic Assembly1 handbook offers a method for quantitatively evaluating a product's ease of assembly by robots. Additionally, it helps the designer estimate the cost of assembly associated with each part, pointing out aspects of part design that incur additional cost. This paper describes robot assembly task time data derived from laboratory tests and industrial experience. It also shows how these data can be substituted for the original values on the handbook data sheets for estimating part assembly times at a two-arm robotic assembly station. Using these new time values, the handbook method yields cycle time estimates that are within 5% of those drawn from computer simulation, while the original data sheet values give estimates that are approximately 20% lower than the computer simulated times. The principal difference is in the amount of time attributed to robot gripper changes.

Recirculatory moment analysis of drugs in man: estimation of extraction ratio and mean cycle time for single systemic and pulmonary circulation.

The extraction ratio (Ec) and the mean cycle times (t^-c) for single systemic and pulmonary circulation were evaluated for 115 drugs in man. Heparin and fluorohydrocortisone, which have the smallest t^-c values (about 1min) show the small Ec values (close to zero). This result suggests that these drugs circulate through the body restricted within the blood vessels. The theoretical considerations indicate that the clearances defined by Ai (∞)/AUC differ from EiQi, where Ai(∞) is the amount eliminated by organ i, AUC is the area under the plasma concentration curve, Ei is the extraction ratio and Qi is plasma flow rate through organ i. The hepatic extraction ratios (Eh) of alprenolol, metoprolol and propranolol calculated from intravenous data alone are large (above 80%). It is also shown that the steady-state volume of distribution (Vss) is rather independent of hepatic and renal extraction ratios, while the mean residence time (MRT) is considerably affected by change of these ratios.

Cell kinetic studies in the epidermis of the mouse. I. Changes in labeling index with time after tritiated thymidine administration.

The changes in the labeling index (LI) with time after a single injection of tritiated thymidine (3HTdR) at each of 4 different times of the day have been studied. Slight differences occur in the shape of these LI curves, (e.g. in the timing of the peaks) depending on the time of day when the initial injection was given. Thus, the time of day influences not only the number of cells in DNA synthesis but also determines the subsequent behavior of the labeled cells. The curves show 3 distinct peaks from which estimates of the cell cycle time can be made. The technique permits the cell cycle time to be estimated. From the data as a whole a minimum cell cycle time of 90 h for basal cells in the epidermis on the back of a mouse is obtained. The technique also provides estimates for the duration of S + G2 + M which varies depending on the time of day that the label is given. The LI curves can best be understood if the basal layer is assumed to contain 2 cell populations with differing cell cycle times; one having a long cell cycle (about 180 h) but short S-phase and containing the stem cells, the other having a short cell cycle (about 90 h) and a long S-phase duration and consisting of transit cells.

Some system implications of a Josephson computer technology

The Josephson Technology as now understood is projected onto a current computer mainframe, the IBM 3033 to estimate its effect. This is a hypothetical projection and should not be taken in any way to represent a planned product. A three cycle critical case path is identified. Then an experimental 2.5-µm Josephson current injection logic (CIL) circuit family and cache memory design are configured into a functionally equivalent Josephson package. Propagation distances in the hypothetical package are estimated to be 6 percent of those in the comparison mainframe; estimated cycle time is 4 ns yielding an internal performance improvement by a factor of > 14. The Josephson version of the IBM 3033 would entail a more than 99-percent reduction in regulated power.

Asymmetrical Division of Saccharomyces cerevisiae in Glucose-limited Chemostat Culture

Saccharomyces cerevisiae S288C/1 was grown in a glucose-limited chemostat at population doubling times (τ) of 80 to 736 min. Estimates of the daughter cycle time (D), the parent cycle time (P) and the budded period (B) were obtained from bud scar analyses and equations derived from the Hartwell & Unger model of asymmetric cell division. D, P and B all showed biphasic linear relationships to τ, quantitatively different from estimates for the same strain in batch culture. Median cell volume and dry weight per cell increased at the faster growth rates, but the average cell density reached a minimum at τ = 150 min. The contiguous array of bud scars on parent cells became increasingly irregular as the doubling time increased from 140 min. At the fastest growth rates a small percentage of filamentous forms were observed due to failure of cells to undergo cell separation.

The kinetics of the formation of a G2 block from tritiated thymidine in phytohemagglutinin-stimulated human lymphocytes.

Flow cytometry (FCM) was used to monitor the radiation effects promoted by incorporated tritiated thymidine (3H-TdR) on phytohemagglutinin (PHA)-stimulated human peripheral blood lymphocytes stained with propidium iodide (PI). Lymphocyte microcultures were continuously labeled or pulse-labeled for various periods of time with different 3H-TdR concentrations. Two types of DNA histogram analyses were performed on unperturbed and 3H]TdR perturbed lymphocytes. The data analyses consisted of statistical analyses between averaged groups of histograms (nonparametric analysis) and cell cycle analyses (parametric analysis) to determine the percentages of cells in G0 + G1, S and G2 + M. The results showed that (a) 3H-TdR when added to proliferating lymphocytes under certain conditions (both short-term continuous and pulse-labeling) caused a highly significant increase in the proportion of tetraploid (4C) cells by FCM, (b) the increase in the proportion of 4C cells represented a block in G2 and (c) the relative increase in the percentage of 4C cells was proportional to 3H-TdR incorporation which was proportional to labeling time and concentration. Therefore, it was concluded that short labeling times be used to minimize adverse radiation effects when 3H-TdR is used to assay substances affecting lymphocyte proliferation or in the estimation of cell cycle time.

Asymmetrical division of Saccharomyces cerevisiae.

The unequal division model proposed for budding yeast (L. H. Hartwell and M. W. Unger, J. Cell Biol. 75:422-435, 1977) was tested by bud scar analyses of steady-state exponential batch cultures of Saccharomyces cerevisiae growing at 30 degrees C at 19 different rates, which were obtained by altering the carbon source. The analyses involved counting the number of bud scars, determining the presence or absence of buds on at least 1,000 cells, and independently measuring the doubling times (gamma) by cell number increase. A number of assumptions in the model were tested and found to be in good agreement with the model. Maximum likelihood estimates of daughter cycle time (D), parent cycle time (P), and the budded phase (B) were obtained, and we concluded that asymmetrical division occurred at all growth rates tested (gamma, 75 to 250 min). D, P, and B are all linearly related to gamma, and D, P, and gamma converge to equality (symmetrical division) at gamma = 65 min. Expressions for the genealogical age distribution for asymmetrically dividing yeast cells were derived. The fraction of daughter cells in steady-state populations is e-alpha P, and the fraction of parent cells of age n (where n is the number of buds that a cell has produced) is (e-alpha P)n-1(1-e-alpha P)2, where alpha = IN2/gamma; thus, the distribution changes with growth rate. The frequency of cells with different numbers of bud scars (i.e., different genealogical ages) was determined for all growth rates, and the observed distribution changed with the growth rate in the manner predicted. In this haploid strain new buds formed adjacent to the previous buds in a regular pattern, but at slower growth rates the pattern was more irregular. The median volume of the cells and the volume at start in the cell cycle both increased at faster growth rates. The implications of these findings for the control of the cell cycle are discussed.

ANALYSIS OF INTESTINAL CELL PROLIFERATION AFTER GUANETHIDINE‐INDUCED SYMPATHECTOMY

ABSTRACTRats were treated with guanethidine‐sulphate every 48 hr from birth until 15 days and then maintained until young adulthood. Sympathectomy was verified by dissection and light microscopic preparation of the superior cervical and coeliac ganglia which showed at least a 78% reduction in the number of perikarya. The effect of the chemical sympathectomy was a decrease in the amplitude of the circadian mitotic rhythm from 44·7 to 27·1%, 67·0 to 25·3% and 54·9 to 24·7%, in the duodenum, jejunum, and ileum, respectively. The shape of the mitotic index curve was altered and the mean mitotic index was significantly decreased (P < 0·01) in all three segments of the small intestine. The mean mitotic index of control intestinal epithelium was 3·2 ± 0·1%, 3·6 ± 0·1% and 4·0 ± 0·1% in the duodenum, jejunum, and ileum, respectively, and 2·3 ± 0·1%, 2·4 ± 0·1%, and 2·5 ± 0·1% in guanethidine‐treated rats. Stathmokinetic estimates of cycle time were obtained by use of the metaphase arrest agent, colchicine. The longest cell generation cycle time (Tc) and lowest mitotic index occurred between 12.00 and 16.00 hours and the shortest Tc and highest mitotic index occurred between 00.00 and 04.00 hours, in all three segments of the small intestine. Guanethidine‐treatment lengthens Tc throughout the small intestinal epithelium and reduces the range of variation in Tc over a 24‐hr period. It is suggested that norepinephrine depletion induced by guanethidine may be the cause of the inhibition in circadian periodicity and that norepinephrine and the sympathetic nervous system may be essential for the maintenance of circadian rhythms in mitotic activity.

The effects of colcemid on mouse bone marrow.

Following Colcemid administration, mitoses accumulate preferentially in the subendosteal region of the bone marrow of the mouse. This finding suggests that the most rapidly proliferating cells are localized to the subendosteal region, and complements previous radioautographic studies which have demonstrated a corresponding labelling gradient in the marrow. Quantitative estimates of cell cycle time by the stathmokinetic method were precluded by the presence of significant Colcemid induced interphase cell loss. Colcemid also affected cell differentiation in the marrow. Following Colcemid administration there was a fall in mature granulocytes in the marrow, and a concommitant rise in marrow megakaryocytes.

Cycling Characteristics of Human Lymphocytes In Vitro

Abstract The cycling characteristics of human peripheral blood lymphocytes in phytohemagglutinin-stimulated cultures were examined by means of a new technique employing radioautographic methods which assay the fraction of cells whose nuclei contain DNA polymerase utilizing exogenous and/or endogenous DNA primer-template capability. The fraction of cells labeled by these techniques increases 5-11 hr prior to the onset of DNA synthesis. Estimates of cell cycle time, G1 time, and fraction of cycling cells are made for the first 4 days in culture. Evidence is presented to support the hypothesis that daughter cells of the first divisions may be retired from cycle by virtue of loss of primer-template availability, rather than by loss of DNA polymerase.

Changes in cell proliferation rate in mouse uterine epithelium during continuous oestrogen treatment.

SUMMARY Fraction of labelled mitoses (FLM) curves were constructed for mouse uterine luminal epithelium during oestradiol treatment; on day 2 when mitosis was high, and on days 4 and 9 when mitosis was low. No difference was found between the duration of DNA synthesis on these 3 days. The distance between the first and second peaks, usually taken as an estimate of the mean cell cycle time, did not change significantly between days 2 and 4, although the labelling index fell from 38 to 8%. The second peaks of the FLM curves became progressively lower on the three days examined, which was consistent with the interpretation that there was a reduction in the probability of transition of cells from G1 (the post-mitotic period) into the replicative phase of the cell cycle, resulting in the observed fall in mitotic index.

Cell development in the anther, the ovule, and the young seed of Triticum aestivum L. var. Chinese Spring

Cell development in the anther, the ovule, and the young seed of <i>Triticum aestivum</i> L. var. Chinese Spring

Comparison of multiple injections with continuous infusion of tritiated thymidine, and estimation of the cell cycle time.

ABSTRACT Labelled nuclei were counted in stratified squamous epithelium in mice killed after 24 h intraperitoneal administration of tritiated thymidine to label cells synthesizing deoxyribonucleic acid. Multiple injections produced the same result as an infusion of tritiated thymidine given after 24 h infusion of saline, but infusion of tritiated thymidine alone produced a different result. Thus, cell proliferation was depressed during the first 24 h of continuous infusion but was normal during the second 24 h. Comparison of proliferation of the oesophageal epithelium at the level of the thyroid and at the level of the diaphragm showed no difference between the two. Comparison of male with female mice given 72-h infusions of tritiated thymidine showed that cell proliferation occurred at the same rate in both. The cell cycle time was estimated in the epithelium of the oesophagus and tongue by comparison of mice given a single injection with mice given multiple injections of tritiated thymidine.

The rate of division of antibody-forming cells during the early primary immune response.

Mitotic blocking agents, colchicine or Velban, were used to estimate cycle times of spleen cells which release hemolysin for sheep erythrocytes (plaque-forming cells). The cells were obtained either from rats immunized with sheep erythrocytes or from cultures of mouse spleen cells immunized in vitro with the same antigen. 2, 3, or 4 days after immunization, animals or cell cultures were treated with mitotic blocking agents for periods of time ranging from 2.5 to 7 hr; plaque-forming cells were then enumerated. Decreased numbers of plaque-forming cells were found after such treatment. The extent of reduction was a function of duration of the drug treatment and the method of immunization, but was independent of the time after immunization. The evidence presented is consistent with premises that: (a) plaque-forming cells in mitosis do not release sufficient antibody to be detected, (b) mitotic blocking agents, by arresting plaque-forming cells in metaphase, prevent not only detection of these cells but also the increase in number of plaque-forming cells which would have resulted from cell division, (c) mitotic blocking agents do not affect release of antibody by cells in interphase. Cell cycle times, based on the extent of reduction of plaque-forming cells per unit time of drug treatment, were estimated using a mathematical model appropriate for an exponentially increasing population of cells. Cell cycle times estimated using the mitotic blocking agents agreed well with cell doubling times calculated from the increase in plaque-forming cells occurring 1-4 days after immunization. Increased responses produced by higher antigen doses or treatment of immunized animals with an adjuvant resulted from an increased rate of division of responding cells and their progeny. The results are consistent with a cell selection theory of antibody formation. Antigenic stimulation causes relatively few cells to proliferate and to synthesize antibody; apparently the magnitude of the response is dependent primarily on the rate of division of responding cells. It is suggested on the basis of observations of in vitro-immunized cell cultures that the rate of division of responding cells may be dependent on the rate of interaction between two cell types, both of which are essential for the in vitro plaque-forming cell response.