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Biomedical subjects

P R Patnaik

Publications and source records attributed to P R Patnaik.

16 recordsLinked to original sources

Synthesizing cellular intelligence and artificial intelligence for bioprocesses.

Microbial processes operated under realistic conditions are difficult to describe by mechanistic models, thereby limiting their optimization and control. Responses of living cells to their environment suggest that they possess some "innate intelligence". Such responses have been modeled by a cybernetic approach. Furthermore, the overall behavior of a bioreactor containing a population of cells may be described and controlled through artificial intelligence methods. Therefore, it seems logical to combine cybernetic models with artificial intelligence to evolve an integrated intelligence-based strategy that is physiologically more faithful than the current approaches. This possibility is discussed, together with practical considerations favoring a hybrid approach that includes some mathematical modeling.

Artificial Intelligence↗

Neural network designs for poly-beta-hydroxybutyrate production optimization under simulated industrial conditions.

Improvement of the fermentation efficiency of poly-beta-hydroxybutyrate (PHB) may make it competitive with chemically synthesized petroleum-based polymers. One step toward this is optimization of fluid dispersion and the feed rates to a fed-batch bioreactor. In a recent study using a fermentation model, dispersion corresponding to a Peclet number of approximately 20 was shown to maximize the productivity of PHB. Here further improvement has been investigated using neural optimization. A comparison of seven neural topologies has shown that while feed-forward and radial basis neural networks are computationally efficient, recurrent networks generate higher concentrations of PHB. All networks enhanced the productivity by 16-93% over model-based optimization.

Bioreactors↗

Effect of fluid dispersion on cybernetic control of microbial growth on substitutable substrates.

Many fermentation media contain two or more substrates, which a microorganism utilizes for similar purposes. Depending on the conditions prior to and during a fermentation, the substrates may be utilized in succession or simultaneously. Since it is difficult to portray this behavior through mechanistic models, a cybernetic method was proposed earlier. Here the microorganism chooses the mode of substrate utilization that maximizes its own survival, usually expressed by the growth rate. In a fully dispersed bioreactor, simultaneous utilization generates higher growth rates but leads to low biomass concentrations since this utilization pattern is preferred at low concentrations of the substrates. In this study it has been shown that by allowing less than complete dispersion in the broth it is possible to shift from sequential to simultaneous utilization at high concentrations, thereby enabling both high growth rates and large biomass concentrations. This strategy thus allows the natural incomplete dispersion in large bioreactors to be gainfully exploited.

Journal Article↗

On the performances of noise filters in the restoration of oscillatory behavior in continuous yeast cultures.

Continuous flow microbial fermentations under industrial conditions are subject to the influx of noise, mainly through the feed stream. Noise upsets the normal deterministic behavior. For continuous cultures of Saccharomyces cerevisiae exhibiting oscillatory responses, four kinds of commonly used noise filters, three algorithmic and one neural, have been compared for their ability to restore noise-free oscillations. An auto-associative neural filter was the best, similar to earlier observations for other organisms under non-oscillatory conditions. This enhances the general applicability of neural filters for industrial scale fermentations.

Algorithms↗

Microbial metabolism as an evolutionary response: the cybernetic approach to modeling.

The growth and metabolic capabilities of microorganisms depend on their interactions with the culture medium. Many media contain two or more key substrates, and an organism may have different preferences for the components. Microorganisms adjust their preferences according to the prevailing conditions so as to favor their own survival. Cybernetic modeling describes this evolutionary strategy by defining a goal that an organism tries to attain optimally at all times. The goal is often, but not always, maximization of growth, and it may require the cells to manipulate their metabolic processes in response to changing environmental conditions. The cybernetic approach overcomes some of the limitations of metabolic control analysis (MCA), but it does not substitute MCA. Here we review the development of the cybernetic modeling of microbial metabolism, how it may be combined with MCA, and what improvements are needed to make it a viable technique for industrial fermentation processes.

Animals↗

Penicillin fermentation: mechanisms and models for industrial-scale bioreactors.

Even after many years of research and industrial practice, the production of penicillin G in fed-batch fermentation by Penicillium crysogenum continues to attract research interest. There are many reasons: the commercial and therapeutic importance of penicillin and its derivatives, the complexity of cell growth, and the impact of engineering variables, the last of which are significant in large bioreactors but are not yet fully understood. Extensive research has generated new information on the mechanisms of cellular reactions and morphological features of the mycelia and their role in the synthesis of the product. Given a choice of mechanisms, models of different degrees of complexity, for both cellular differentiation and bioreactor performance, have been proposed. The more complex models require and provide more information. They are also more difficult to evaluate and apply in automatic control systems for production-scale bioreactors. The present review considers the evolution of recent knowledge and models from this perspective.

Bioreactors↗

Are microbes intelligent beings?: An assessment of cybernetic modeling.

Microorganisms growing in a multi-substrate medium have different and varying preferences for the various components of the medium. The preferences depend on the operating conditions and the substrates may be utilized sequentially or simultaneously. Sometimes an organism may change its preferences among substrates and/or switch between sequential and simultaneous utilization. These aspects are difficult to describe through models based on chemical and physical laws alone. Cybernetic modeling ascribes to microorganisms the ability to perceive their environment (i.e. the growth medium) and make 'intelligent' choices regarding substrate utilization to maximize an objective, which is usually the growth rate. This article reviews the development of cybernetic modeling since it began in 1982. Different workers have suggested different perspectives of how microbes make optimal use of their resources. These are discussed and future directions for improvement are indicated.

Journal Article↗

Penicillin fermentation: mechanisms and models for industrial-scale bioreactors.

Even after many years of research and industrial practice, the production of penicillin G in fed-batch fermentation by Penicillium crysogenum continues to attract research interest. There are many reasons: the commercial and therapeutic importance of penicillin and its derivatives, the complexity of cell growth, and the impact of engineering variables, the last of which are significant in large bioreactors but are not yet fully understood. Extensive research has generated new information on the mechanisms of cellular reactions and morphological features of the mycelia and their role in the synthesis of the product. Given a choice of mechanisms, models of different degrees of complexity, for both cellular differentiation and bioreactor performance, have been proposed. The more complex models require and provide more information. They are also more difficult to evaluate and apply in automatic control systems for production-scale bioreactors. The present review considers the evolution of recent knowledge and models from this perspective.

Bioreactors↗

Characterization and some reaction-engineering aspects of thermostable extracellular beta-galactosidase from a new Bacillus species.

A new strain of Bacillus sp. was isolated from a hot water spring in India. This strain generated a high activity of extracellular beta-galactosidase at 37 degrees C in shake flasks. The beta-galactosidase activity was found to increase continuously but the production rate was slower than with some other organisms reported in the literature. There were noteworthy differences in the time-domain profiles of bacterial concentration and beta-galactosidase activity when the starting concentration of substrate (glucose) was tripled from 10 g/L. These differences may be explained in terms of the relative rates of enzyme synthesis and its diffusion across the cell wall. The enzyme produced by this organism is more stable than other beta-galactosidases; its half-life is 408 h at 50 degrees C and 94 h at 55 degrees C, while the reported enzymes showed perceptible loss of activity within 2 h.

Bacillus↗

Applications of neural networks to recovery of biological products.

Artificial neural networks (ANN) are being applied to recovery of products from fermentation broths. Recovery methods for which mathematical models are complex or non-existent are particularly suitable for control and analysis by ANNs. Use and potential of artificial neural networks for product recovery applications are reviewed.

Journal Article↗

Extracellular amylase production by Saccharomycopsis capsularis and its evaluation for starch saccharification.

A strain of starch-assimilating yeast, Saccharomycopsis capsularis, isolated from Indian cereal-based fermented foods, produced significant levels of extracellular alpha-amylase and glucoamylase. The enzymes reached their peak activities during the stationary phase at the end of the 5th and 4th day of cultivation, respectively. The amylase yields were maximized by a proper choice of carbon and nitrogen sources, starting pH of the culture medium and growth temperature. High activities of the enzymes were obtained through inexpensive agricultural commodities, such as wheat bran and corn meal as carbon sources, and defatted soybean meal and peanut meal as nitrogen sources. A temperature of 28-32 degrees C and an initial pH of 4.5-5.0 were optimum. The crude amylase mixture could liquefy and saccharify a 1% starch solution completely in 24 h at 50 degrees C.

Amylases↗

Uniqueness and multiplicity of steady states in monocyclic enzyme cascades: a graph-theoretic analysis.

Monocyclic enzyme cascades are important regulators of biochemical reactions in living cells. The reaction network may have either one steady state or many, depending on its structure. The occurrence of multiple steady states has important biological implications. A simple graph-theoretic method has been applied to five reaction mechanisms--which together cover many common monocyclic cascades--to determine which mechanisms generate just one steady state and which ones allow more than one state. It is shown that an unstable steady state in a multiplicity region can be usefully exploited and that in some cases transitions may occur between uniqueness and multiplicity regions. The possible effects of such transitions are discussed.

Animals↗

Liquid emulsion membranes: principles, problems and applications in fermentation processes.

Liquid emulsion membranes (LEMs) have developed into a versatile technique for a variety of applications involving selective and controlled transport of biochemicals. Biological applications cover the controlled delivery of drugs from capsules, detoxification of the circulatory system, recovery of useful compounds from waste streams and selective separation of products from fermentation broths. This review traces the development of LEMs, discusses their key features, advantages and limitations, describes methods of modelling LEM systems and highlights some applications with industrial potential. Two kinds of LEM systems are considered. The first type are agitated emulsions, which are relatively easy to prepare and use but may be limited in their selectivity and long-term stability. Supported liquid membranes (SLMs) are a recent development; they use porous solid supports and have excellent stability and selectivity. Their chemical engineering aspects and applications in fermentation processes are considered.

Journal Article↗

Micromixing and the steady-state performance of bioreactors using recombinant bacteria--analysis through a reversed two-environment model.

A reversed two-environment model has been used to study micromixing in continuous fermentation for growth and product formation by recombinant bacteria. As an example, an Escherichia coli M72 strain harbouring the plasmid pPLc23trpA1 and producing tryptophan synthetase is considered. With excess substrate, 10% plasmid-free bacteria in the initial broth do not affect the steady-state concentrations of plasmid-containing bacteria but their mass fractions decrease significantly. With a smaller substrate concentration, the mass fractions decrease sharply as the dilution rate increases if micromixing is good; but concentrations still remain high. There is also a clear demarcation between regions of good and poor micromixing. These results are explained and an optimal combination of micromixing and dilution rate is suggested to maximise productivity.

Bacteria↗

A geometric interpretation of the feasibility of reactive extraction/re-extraction of penicillin G.

The reactive extraction (re-extraction) of penicillin G from reaction mixtures is based on complexation with a carrier and subsequent dissociation of the complex. An established mathematical model for this has been analysed to develop a feasibility domain within which the process may be designed and optimised. Geometric and physical interpretations of this domain are provided.

Drug Carriers↗

Some features of oscillatory glycolysis in coupled reactors.

Glycolysis in two chemostats coupled by a recycle stream has been mathematically analysed for regions of oscillation. In the space of the residence times in the two reactors and the recycle ratio, it is seen that the oscillatory region shrinks as any one of the parameters increases. Further, there is an optimal recycle ratio at which the build-up of ATP is maximum.

Adenosine Triphosphate↗