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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 20 (1978), S. 349-381 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: This paper describes a mathematical model of the lag phases of Saccharomyces cerevisiae that incorporates the basic concepts previously presented in a two-stage deterministic model for the growth of this organism under conditions of oxygen excess with a sugar as the growth-limiting substrate. The model structure was suggested by an extensive investigation of the causes of the lag phases of S. cerevisiae which found that, in contrast to the traditionally accepted trends, the length of the lag phase was not inoculum-size dependent. This was consistent with other previously published work which suggested that a major factor in the length of the lag phases in S. cerevisiae was the need to synthesize adequate levels of glycolytic and respiratory enzymes. These suggestions were confirmed experimentally with lag-age data. Based on this conclusion a mathematical model was developed incorporating a description of the levels of glycolytic and respiratory enzymes and their effect on the growth rate and metabolism. This model was tested experimentally and the initial results indicate indicate that many aspects of the lag phase of this organism may be described mathematically. The experimental findings further support the concept of primary regulatory control proposed by Bijkerk and Hall.
    Additional Material: 10 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 21 (1979), S. 609-626 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A complete carbon and redox balance for Saccharomyces cerevisiae grown in batch culture with ethanol as the limiting carbon and energy source is reported. A novel method, which allowed the determination of carbon dioxide contained in the culture medium and biomass, is described and revealed amounts considerably in excess of what was expected from equilibrium data. Furthermore, elemental composition of the biomass was used to calculate the amount of oxygen required for biosynthetic reactions. When these corrections are applied to experimentally measured gas metabolism data, apparently anomalous results are shown to be consistent with the overall metabolism of bakers' yeast. These findings have wide implications to the quantitative study of the metabolism and energetics of facultative aerobes.
    Additional Material: 3 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 23 (1981), S. 1735-1762 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A mathematical model for the aerobic growth of Saccharomyces cerevisiae in both batch and continuous culture is described. It was based on the experimental observation that the respiratory capacity of organism may become saturated and exhibit a maximum specific oxygen uptake rate after suitable adaptation. This experimental observation led to the possibility that transport into and out of the mitochondrion was of major importance in the overall metabolism of S. cerevisiae and was subject to long-term adaptation. Consistent with this observation a distributed model was proposed which. as its basis, assumed the control of repression or inhibition of the uptake rates of other substrates. No other regulation of fermentation and respiration was assumed. The model provided a suitable structure allowing precise quantification of the changes in rate and stoichiometry of energy production. The model clearly indicated that growth under the wide range of experimental conditions reported could not be predicted using constant values for the maximum specific respiratory rate of constant values of YATP (g biomass/mol ATP) and PO ratio of (mol ATP/atom oxygen). The causes of the variation in the respiratory rate were not determined and it was concluded that a more detailed analysis (reported subsequently) was required. The variation of YATP and PO ratio with specific growth rate implied that the efficiency of ATP generation or ATP utilization decreased with increasing specific growth rate. It was concluded that it was not possible to quantify the individual effect of YATP and PO ratio until independent means for their reliable estimation is available.
    Additional Material: 12 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 23 (1981), S. 1763-1795 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A computer simulation of the integration of the internal energy metabolism and the cell cycle of Saccharomyces cerevisiae is described. This was attempted, for the first time, as a result of the observation that in this organism the overall or average external metabolic exchange rates often differed considerably from the internal metabolic fluxes which they are normally assumed to represent. This was the result of such factors as the variation in the nature of the metabolism of the organism depending on its stage in the cell cycle and redox interactions between anabolism and catabolism. The overall result of this simulation is the prediction of the internal metabolic fluxes consistent with the experimentally determined external fluxes. While these simulation depend on the assumption regarding the energetics and cell cycle of Saccharomyces cerevisiae, they provide a means of examining with precision such processes as the energetics of cell growth and cell cycle variation. As a result, within these limitation, they allow the systematic study of coordinated cell control. Such an approach provides a useful and largely unused adjunct to the experimental approaches which have attempted the study of coordinated metabolic regulation.
    Additional Material: 13 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 24 (1982), S. 847-856 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The accuracy of kinetic and stoichiometric data obtained from most laboratory-scale continuous-culture equipment, particularly involving gaseous measurements, may be much lower than many workers realize, despite the use of good quality instruments. For example, errors in specific oxygen uptake measurements (QO2) easily can be as high as ±100%. This article assesses the accuracies of individual instruments and of the overall system in greater detail than has previously been reported and suggestions are made as to how the errors can be reduced to acceptable levels.
    Additional Material: 1 Ill.
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 35 (1990), S. 907-920 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A general model for aerobic yeast growth in batch culture is presented. It is based on the concept that the aerobic metabolism of all yeasts is determined by the relative sizes of the transport rate of sugar into the cell and the transport rate of respiratory intermediates into the mitochondrion. If the rate of sugar uptake rate exceeds the rate of transport of respiratory intermediates into the mitochondrion (as in Saccharomyces cerevisiae, S. uvarum, and S. pombe), the metabolism exhibits the features of ethanol excretion and limited specific oxygen uptake rate. If the rate of transport of respiratory intermediates into the mitochondrion is of the same order as the transport of sugar into the cell (as in Candida utilis), the metabolism is characterized by little or no ethanol excretion and a much higher specific oxygen uptake rate. Batch data from an extensive range of yeast and carbon sources is used to illustrate the use of this model. The ability of this model to fit such an extensive range of experimental data suggests that it can be used as a generalized model for aerobic yeast growth.
    Additional Material: 22 Ill.
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  • 7
    ISSN: 1573-0778
    Keywords: biotechnology ; dynamic modeling ; fermentation processes ; optimization ; simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The infection of insect cells with baculovirus was described in a mathematical model as a part of the structured dynamic model describing whole animal cell metabolism. The model presented here is capable of simulating cell population dynamics, the concentrations of extracellular and intracellularviral components, and the heterologous product titers. The model describes the whole processes of viral infection and theeffect of the infection on the host cell metabolism. Dynamic simulation of the model in batch and fed-batch mode gave goodagreement between model predictions and experimental data. Optimum conditions for insect cell culture and viral infectionin batch and fed-batch culture were studied using the model.
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  • 8
    ISSN: 1573-0778
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract An analysis of batch and continuous kinetic data obtained from hybridoma cell cultures has been performed with particular reference to the existence of specific antibody production profiles. The results presented by several groups, including our own, have been studied. Our analysis suggests that different interpretations of the data can be made to those previously presented in the literature. In view of the significance of these profiles, particularly in terms of production strategies designed to maximise antibody production, we believe that more consideration needs to be given to accuracy in reporting of kinetic studies in the future.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cytotechnology 2 (1989), S. 163-170 
    ISSN: 1573-0778
    Keywords: aeration ; agitation ; hybridoma cells ; mammalian cell cultivation ; polymer addition ; shear
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract Three different hybridoma cell lines, grown in serum-free media with different levels of Pluronic F-68, were subjected to a shear force of 0.6 N m-2. Some protective effect due to the polymer was found, indicating it to be a potentially useful adjuvant in serum-free media. Other observations of liquid and gas effects at the reactor level have been included here. A discussion of the difference between suspension and microcarrier cultures, in relation to hydrodynamic effects, is included.
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  • 10
    ISSN: 1573-0778
    Keywords: hybridoma ; monoclonal ; productivity ; batch ; continuous ; perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract A major variable to consider in the production of biologicals from mammalian cell cultures is the mode of operation, be it a batch, continuous, perfusion, fed-batch or other production method. The final choice must consider a number of fundamental and economic issues. Here we present some antibody production data from different cell lines using different modes of production and discuss the important factors for consideration in choosing a production strategy. It was found that the productivity of batch cultures was lower than that obtained in continuous and perfused cultures, but that productivity could be improved by implementing suitable feeding strategies. The antibody productivity of one cell line, MCL1, during exponential phase was not affected by media type or glucose level. The maximum productivity of two cell lines in continuous culture was found to occur at dilution rates below the maximum, from 0.019 to 0.030 hr−1.
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