Bacteria and yeasts have been the organisms of choice for the industrial production of heterologous recombinant proteins for many years. The ability to cultivate bacterial strains to high cell density at large scale has become an increasingly important technique throughout the field of biotechnology, from basic research programmes (structural or kinetic studies) to large-scale pharmaceutical production processes. Escherichia coli remains one of the most attractive organisms for the production of recombinant proteins (see Chapters 4, 5, and 21 for examples) where no complex post-translational modifications (e.g. glycosylation or disulphide bond formation) are required for biological activity and because its genetics and physiology are well understood. However, there are important drawbacks associated with the use of prokaryotic organisms. The low percentage of GC nucleotides in their genomes, when compared to mammalian genes, and the existence of rare codons that often result in low expression levels or inactive truncated forms and, in many cases, proteins are expressed as insoluble inclusion bodies in the bacterial periplasmic space. Bacteria are also incapable of carrying out any post-translational modifications, which strongly influences protein stability, folding, solubility and, hence, its biological activity. Yeasts (e.g. Saccaromyces cerevisiae or Pichia pastoris), though, can perform some post-translational modifications similar to those of the more complex eukaryotic cells (see Chapter 5). However N-glycosylation of mammalian proteins in yeast seems to be very inefficient. Additionally, both bacteria and yeast cells are surrounded by a mechanically strong cell wall that may hinder recovery of any non-secreted proteins.
Recent research is making progress in framing more precisely the basic dynamical and statistical questions about turbulence and in answering them. It is helping both to define the likely limits to current methods for modelling industrial and environmental turbulent flows, and to suggest new approaches to overcome these limitations. This chapter had its basis in the new results that emerged from more than 300 presentations during the programme held in 1999 at the Isaac Newton Institute, Cambridge, UK, and on research reported elsewhere. The objective of including this material (which is a revised form of an article which appeared in the Journal of Fluid Mechanics – Hunt et al., 2001) in the present volume is to give a background to the current state of the art. The emphasis is on the physics of turbulence and on how this relates to modelling. A general conclusion is that, although turbulence is not a universal state of nature, there are certain statistical measures and kinematic features of the small-scale flow field that occur in most turbulent flows, while the large-scale eddy motions have qualitative similarities within particular types of turbulence defined by the mean flow, initial or boundary conditions, and in some cases, the range of Reynolds numbers involved. The forced transition to turbulence of laminar flows caused by strong external disturbances was shown to be highly dependent on their amplitude, location, and the type of flow.
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