Volume 8, suppl.
Selected papers from 20th Anniversary International Symposium "Bioprocess Systems 2007 - BioPS'07"
Opening Speech
Modelling and Control of Bioprocess Systems
Mathematical Modeling of Metabolic Processes in a Living Organism in Relation to Nutrition1-12
Dimitrova N., Markov S.
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The paper is devoted to the mathematical modeling of metabolism and nutrition based on enzyme-kinetics reactions described by Michaelis-Menten equations. Proposed are simple models of metabolic processes in a living system which explain certain effects related to various regimes of nutrition and fasting.
Brunovsky Normal Form of Monod Kinetics Models and Growth Rate Control of a Fed-batch Cultivation Process13-26
Pavlov Y.
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A mathematical methodology that gives assistance to design of fed-batch stabilization and control is presented. The methodology is based both on Utility theory and optimal Control theory. The Utility theory deals with the expressed subjective preferences and allows for the expert preferences to be taken in consideration in complex biotechnological systems as criteria for control and optimization. The Control theory is used for parameters stabilization of a fed-batch cultivation process. The control is written based on information of the growth rate. The simulations show good efficiency of the control laws.
Software EpiData - Applications for Needs of Biotechnological Processes27-36
Ljakova K.
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EpiData (free software for entering and documenting data) is presented. Some aspect of this software is shown for needs of database system (DB) and information systems (IS) that can be used in bioprocess system.
A System for Functional States Recognition of Escherichia coli Fed-batch Cultivation37-46
Ljakova K., Roeva O., Tzonkov St.
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EpiData (free software for entering and documenting data) is used for design a system for functional states identification based on specific metabolic mechanisms.
Noise Reduction of Measurement Data using Linear Digital Filters47-58
Roeva O., Ljakova K., Hitzmann B., Tzonkov St.
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In this paper Butterworth, Chebyshev (Type I and II) and Elliptic digital filters are designed for signal noise reduction. On-line data measurements of substrate concentration from E. coli fed-batch cultivation process are used. Application of the designed filters leads to a successful noise reduction of on-line glucose measurements. The digital filters presented here are simple, easy to implement and effective - the used filters allow for a smart compromise between signal information and noise corruption.
Application of the Theory of the Structure of the Stream Flow for Modeling of Stirred Tank Bioreactors59- 68
Petrov M.
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In this paper, investigations of the structure of the stream-flow in a lab scale stirred tank bioreactor are developed with the relevant research methods. The choise on the following statistical criteria: Fisher function, correlation coefficient, and relative error is developed. The best results at low impeller speed are received at a model with stagnancy zone. The obtained results are used for modeling of a stirred tank bioreactor.
Modelling and Management of Ecosystems
Prognostication of Ozone Concentration in the Air69-76
Nedialkov D., Angelova M., Krastev A., Hristova H.
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The relation between the ozone concentration and the meteorological parameters is investigated using a real data. A maximal hourly concentration for a day prognostication method is proposed. An initial prognosis is made by the use of regression methods which apply only the meteorological parameters. The prognosis is updated on every hour and here besides the meteorological parameters the last measured ozone concentration is used.
Modeling and Prognosis of the Strouma River Pollution77-86
Ilkova T., Petrov M.
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A model for analysis and prognosis of river quality has been developed, which is a modified method of the time series analysis has been applied for an assessment and prognosis of water pollution of the Strouma river. The following indexes of the water pollution of the Strouma river have been investigated: BOD, oxidation, soluble and insoluble substance – the village of Marino Pole. Periodical seasonal and annual pollution variations have been determined, as well as basic tendencies in the evolution of the water quality for the period from years 2001 to 2003. A prognosis of the river pollution for the year 2004 has been made. The received results show the offered times series analysis modified method successfully could be used for modeling and prognosis of the water pollution of the river ecosystems.
An Algorithm for Modified Times Series Analysis Method for Modeling and Prognosis of the River Water Quality87-94
Ilkova T., Petrov M.
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An algorithm and programs for modeling, analysis, and prognosis of river quality has been developed, which is a modified method of the time series analysis (TSA). The algorithm and program are used for modeling and prognosis of the river quality of Bulgarian river ecosystems.
Modelling in BIology and Medicine
Qualitative Analysis of Somitogenesis Models91-104
Petrov V., Wierling C., Maschke-Dutz E., Herwig R.
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Although recently the properties of a single somite cell oscillator have been intensively investigated, the system-level nature of the segmentation clock remains largely unknown. To elaborate qualitatively this question, we examine the possibility to transform a well-known time delay somite cell oscillator to dynamical system of differential equations allowing qualitative analysis.
Investigation of Dynamic Behaviour of Receptor Tyrosine Kinase and Protein Tyrosine Phospatase Reaction Network using Mathematical Model105-114
Nikolov S., Vera J., Wolkenhauer O., Petrov V.
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The dynamic and bifurcation behaviour of receptor tyrosin kinase (RTK) and protein tyrosine phospatase (PTP) reaction network model is investigated on the basis of Lyapunov-Andronov’s theory. According to our qualitative and bifurcation analysis, propagation of phosphorylation is only possible in the unstable regime of the reaction network, i.e. when kinase activity of the receptor increases on phosphorylation. For some values of the model parameters first Lyapunov value can be positive or negative and bistability takes place.
Influence of RKIP Protein Complexes Concentrations on the Quasi-Stationary Behaviour of the MEK/ERK Signal Transduction Pathway115-122
Nikolova E., Petrov V.
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It is considered the quasi-stationary approximation of a dynamic model, representing a positive feedback mechanism in the MEK/ERK signaling pathway mediated by RKIP. An analytical solution of the eight dimensional quasi-stationary system is found. Analytical relations between stationary and initial values of all signal pathway components are derived too. On the basis of them it is established that the quasi-stationary behaviour of a MEK/ERK pathway is dependent only on reactions of association and dissociation of the double phosphorylated protein ERKpp and the protein complex RKIP/Raf-1 to the three-component complex ERKpp/RKIP/Raf-1 and vice versa. Moreover, the leading role of initial concentrations of the RKIP protein complexes is determined.
Dynamical Behaviour of a Time Delay Model of the ERK and STAT5 Interaction123-132
Kotev V.
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In this paper we have done sensitive analysis of a time delay model which describes the ERK and STAT5 interaction. The results show that the type of the equilibrium point of the model can be a compound saddle-focus or a compound saddle-knot. This means that the model is structurally unstable. From the biological point of view in case of interactions between ERK and STAT the proto-oncogenes may turn into oncogenes.
A Deficit of ATP-ase Subunit 8: with Contribution for Two New Cases133-137
Stancheva M., Radeva B., Naumova E., Mihailova S.
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In two consanguineous children brother and sister were reported rare mitochondrial disorder caused by mutation of the gene of MT-ATP8: base change T8412C, with aminoacid change: methionin - threonine which wasthe cause for decreased activity of the synthesized protein (enzyme) and to dysfunction of central nervous system and muscle of the affected children. These cases give us the base to recommend children with muscle hypotonia, mental retardation with unknown cause to be hospitalized in Clinical genetics for confirmation of the diagnosis and careful genetic consultation. The foundation of new rare mitochondrial disease of ATP synthase subunit 8 deficiency is useful in Pediatrics and permit treatment and prenatal diagnosis of the family.
Biotechnology and Bioengineering
Adsorption of Oxaliplatin by Hydroxyapatite138-145
Betsiou M., Sikalidis C., Papageorgiou A.
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Hydroxyapatite (HAP) is the main inorganic component of human skeleton. The last years a lot of interest is focused on its use as drug carrier. In this work the in vitro adsorption of the anti-cancer drug oxaliplatin, by HAP, from its aqueous solution was studied. Various initial concentrations of oxaliplatin aqueous solutions were used in order to determine the maximum adsorption capacity of HAP. Oxaliplatin’s concentrations were determined through Pt determinations by atomic absorption spectrometry with flame technique, in the equilibrated solutions after shaking for 48 hours and filtering the HAP-oxaliplatin slurries. The maximum adsorption capacity was found to be 49.1 mg oxaliplatin/g HAP. In order to determine the time needed for the maximum adsorption to be achieved, six oxaliplatin – HAP slurries were prepared. The slurries had initial oxaliplatin concentrations the one that corresponds to the maximum adsorption capacity of the HAP added. The oxaliplatin determination was carried out after 0, 10, 20, 30, 40 and 48 hours in each different slurry. The maximum adsorption capacity was achieved after 20 hours. The adsorption of oxaliplatin by HAP was found to follow the Freundlich equation.
Biometanation of Distillery Wastewater in an Anaerobic Baffled Reactor System146-153
Bozadzhiev O. E., Valchevski I., Lalov I. G.
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Anaerobic digestion is an established technology for distillery effluent treatment witch seems to be a promising alternative for Bulgarian industry. In this study the methanogenic activity of two different naturally formed microbial consortiums was compared. The better one was used to start continuous anaerobic digestion of high-strength distillery wastewater (COD 85 520 mgO2 . l-1) in laboratory scale anaerobic baffled reactor system. The average applied organic loading rate and hydraulic retention time were 4.28 kg COD m-3. d-1 and 20 d respectively. A COD reduction of about 98% and specific methane production of 0.39 m3. kg-1 CODremoved were reached. Effects of different inhibitory factors such as low pH and presence of oxygen were investigated. In spite of unfavorable factors were applied simultaneously after an adaptation period the reactor showed stable response. The results obtained show the feasibility of this anaerobic process for distillery effluent treatment, representing a valid option to up-grade the existing wastewater treatment processes.
Application of Phanerochaete chrysosporium 1038 - Enzyme Complex and Laccase in Biobleaching Flax Fibers154-161
Georgieva N., Betcheva R., Yotova L., Hadzhiyska H.
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Bleaching processes in textile industry require to keep fibers tenacity, partially to preserve the pectin and reducing the lignin content, that gives color to row flax fibers. The use of lignocellulose-degrading enzymes from basidiomycete Phanerochaete chrysosporium 1038 strain and pure Laccase from Biocatalyst in flax fibers treatment was studied. The whiteness of enzymatically-processed fibers was significantly improved and the residual quantity of nondegraded lignin was less than obtained with chemical processing. The structural changes in the flax fibers during enzyme treatment were determined with IR spectroscopy, which confirmed the lignin degradation.
Biosensor for Pesticides Based on Valerolacton Copolymer162-171
Marinkova D., Yaneva S., Yotova L., Mateva R.
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A construction of amperometric biosensor based on immobilized acetycholinesterase and cholin oxidase is described and its application in the detection of organophosphate pesticides through enzyme inhibition measurements is discussed. The bioactive component of the sensor consists of acetycholinesterase or cholin oxidase covalently immobilized on two types new polymeric synthetic membranes. Two types of the copolymers were used for the synthesis of membranes - the copolymer of polyacrylamide and acrylonitrile and the new copolymer of poly-(hexanlactam)-co-block-poly-(δ-valerolactone) with aliphatic polyester. It is investigated the technical characteristics of biosensor like, response time, linear range and operating stability. The factors affecting the inhibition and reactivation processes were investigated too.
Immobilization of Biocatalysts and Cells on Hybrid Membranes Syntheses on Sol-gel Method172-183
Yaneva S., Marinkova D., Yotova L., Samuneva B.
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The investigations in the area of enzyme action in the living organisms give us the opportunity for applications of these biochemical catalysts in the different purposes of medicine, industry and analytical practice. Using of soluble enzymes is connected with many difficulties, because the enzymes are no regenerative and they are instability. By immobilization of the enzymes on to different carriers the more of these problems are overcome. The application of soluble enzymes caused many difficulties, by the reason that the enzymes can not be regenerated. The immobilization of the enzymes by means of different reagents and carriers overcomes this problem. The aim of this study to develop a sol-gel method of synthesis of new hybrid membrane, with immobilized biocatalysts (microbial cells and enzymes) for biosensor construction. This study shows that hybrid organic-inorganic membranes were synthesized.
Development of Plant Model to Study Biological Effects of Nanodilutions184-192
Kosturkova G.P., Delinick (Delinikou) A.N.
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Pea (sativum)as a model plant has been used extensively in fundamental research in different biological sciences. vivo vitro models were used, as well, to study stress factors. Applying environment friendly technologies for overcoming biotic/abiotic stress increases its importance for sustainable agriculture. In this respect studies in the field of nanotechnology can contribute to solve some problems and to understanding of phenomena or practices that still lack methodology or specific instrumentation for scientific explanations. The interest to such studies was provoked by attempting an explanation on the potentization process and its therapeutic effect, and also by the possibility to apply similar approach in sustainable agriculture. The objectives of the experiments were to examine if potentized nanodilutions (PNDs) have effects on different stages of seed development of pea aiming at the development of a plant model. Copper was chosen as stress factor as its excess is toxic and affects seed development. The experiments show for the first time that potentized nanodilutions (PNDs) of metallic copprer have biological effects on pea seed development which are similar to the effect of copper (water solutions of CuSO4). The results, also, show that PNDs can stimulate response for overcoming the stress applied to seeds.
Variation in in vitro Response to Growth Regulators in Soybean Genotypes from India and Bulgaria193-200
Nedev T., Todorova R., Kosturkova G., Akitha Devi M.K., Sakthivelu G., Giridhar P., Rajasekaran T., Ravishankar G.A
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Soybean (max (L.) Merrill.) is receiving great global importance due to its nutraceutical value but its cultivation suffers the problems of biotic/abiotic stress. To improve soybean germplasm biotechnological approach can be applied. The objectives of the experiments were to study the possibilities for establishment of in vitro cultures which can be used for genetic manipulations and modelling of stress. In vitro morphogeneic response of two Indian (Hardee and JS 335), one Bulgarian (Daniela) and one american (Hodson) soybean cultivars were studied using plant growth regulators. Using cotyledonary nodes as explants, high organogenic response was observed for cv Daniela and cv Hodson on media containig BAP and IBA. TDZ induced multiple shoot buds in all the cultivars, with varying degree of response and it was found to be genotype specific. A maximum of 8 shoot buds were obtained from cotyledonary node explants in presence of TDZ (0.5 mg/l) for the cv. Hardee. A negative correlation was observed between bud number and size for the Bulgarian cultivars. The results indicate the stimulating effect of TDZ on organogenesis and the interaction of genotype and culture media, which can be utilized for crop improvement using tissue culture techniques.
In vitro-differentiation of Embryonic Mammalian Cells as a Material Base for Gene-engineering Manipulations201-206
Sainova I.
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In in vitro-cultivation and infection of cells from the mammalian cell line EBTr, derived from embryonic bovine trachea, with low initial titers of the DNA vaccine avian pox viral strains FK and Dessau, pathological changes in the inoculated cells were not observed or they were slight. On the other hand, differences between the cells from this line were observed independently of presence or absence of virus infection and they were probably due to their further differentiation. These results indicated that, so applied, the used heterologous for mammals and/or mammalian cells vaccine virus strains, are probably non-pathogenic for them. In agreement with literature data, such safe viral strains might be used for transduction of genes in in vitro- and/or ex vivo-cultivated stem/progenitor cells, by obtained on their bases virus gene constructs.

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