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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Meteorology and atmospheric physics 63 (1997), S. 31-38 
    ISSN: 1436-5065
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Summary This paper presents a brief overview of a few variable resolution techniques in the context of the horizontal discretization of the meteorological equations. These are the grid refinement method, the static and dynamic coordinate transformation methods and the variable resolution in physical space method. The latter is illustrated by a variable resolution reformulation of the popular C-grid discretization suitable for use in a limited area model.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 51 (1996), S. 613-623 
    ISSN: 0006-3592
    Keywords: adenovirus ; 293S cells ; protein production ; lactate ; osmolarity ; fed-batch ; glucose control ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The human adenovirus/293S cell expression system is used for the production of either recombinant protein or adenovirus vectors for use in gene therapy. In this work, the production of protein tyrosine phosphatase (PTP1C) was used as a model for the scale-up of both applications. Maximum specific production of 30 to 45 μg of active protein/106 cells was maintained upon infection with adenovirus vectors at cell densities between 2 × 106 to 3 × 106 cells/mL in a 3.5-L bioreactor. This was achieved by resuspending the culture in fresh medium at infection time. The pH was kept at 7.0 throughout the experiment and, at 24 h postinfection, glucose and essential amino acids were added. Attempts to replace the complete change of medium at the time of infection with nutrient supplementation of the used medium led to lower production levels, suggesting that protein expression was limited not by the absence of a key nutrient but by inhibitory factors. Two potentially inhibitory factors were investigated: lactic acid accumulation and increased osmolarity. Medium acidification such as that which would be brought about by lactic acid accumulation was shown to depress PTP1C production. The lactate molecule itself decreased the cell viability when added in concentrations of 20 mM or more. But the specific productivity was affected at higher lactate concentrations of 40 mM or more. Additions of glucose, amino acids, and NaHCO3 used to control pH, led to increases in osmolarity. Osmolarities above 400 mOsm lowered cell density. However, specific production was not significantly affected below 500 mOsm. But, at 500 mOsm, PTP1C production peak was shifted from 48 to 72 hpi. Because of the cell loss, this per cell yield increase did not translate into higher volumetric production. When glucose concentrations was kept at 5 mM by fed-batch addition, lactate production and increases in osmolarity were reduced. In shake flasks, this method permitted maximum production with cells resuspended either in fresh or spent medium at infection. This fed-batch process was implemented successfully at the 3.5-L scale. Fed-batch with glucose may provide a means to increase infected-cell density beyond 3 × 106 cells/mL.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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