Bioautomation

Volume 13, Issue 4
In this issue, the Editorial Board of the journal decided to publish the full texts of the communications presented at the 1st National Conference with International Participation on Biomedical and Bioprocess Engineering - BM&BPE'09, held on 3-4 December 2009 in the Centre of Biomedical Engineering, Bulgarian Academy of Sciences.
Forthcoming calls
22nd International Symposium "Bioprocess Systems": BioPS'2010
14th International Conference on Intuitionistic Fuzzy Sets: ICIFS'2010
Analysis and Processing of Biomedical Signals and Data
Transformerless High-Quality Electrocardiogram and Body Impedance Recording by an Amplifier with Current-Driven Inputs	1-6
Dobrev D., Neycheva T., Mudrov N. [ +/- abstract ][ full text ]
Measurement and recording of changes in bioelectrical impedance in vivo has become a widely used method with various clinical applications. It includes basal impedance Z_o, relative changes ∆Z or its derivative dZ. Many applications related to cardiac and respiratory function require simultaneous electrocardiogram, impedance cardiogram and/or respiration signals recording and analysis. Accurate recording of body impedance is limited by high common mode voltages at the amplifier inputs combined with the influence of the output impedance of the used current source. A circuit concept for a simultaneous high-quality electrocardiogram and bioimpedance acquisition is proposed, profiting from advantages offered by a previously specially designed amplifier with current-driven inputs, yielding to low common mode and high differential mode input impedances.
High-Q Bandpass Comb Filter for Mains Interference Extraction	7-12
Neycheva T., Dobrev D., Mudrov N. [ +/- abstract ][ full text ]
This paper presents a simple digital high-Q bandpass comb filter for power-line (PL) or other periodical interference extraction. The filter concept relies on a correlated signal average resulting in alternating constructive and destructive spectrum interference i.e. the so-called comb frequency response. The presented filter is evaluated by Matlab simulations with real ECG signal contaminated with low amplitude PL interference. The made simulations show that this filter accurately extract the PL interference. It has high-Q notches only at PL odd harmonics and is appropriate for extraction of any kind of odd harmonic interference including rectangular shape. The filter is suitable for real-time operation with popular low-cost microcontrollers.
Study on the Switching Time-Variation of Simultaneously Controlled IGBT: Case of Defibrillators Design	13-18
Mudrov T., Kostov J. [ +/- abstract ][ full text ]
Samples of integrated gain bipolar transistors (IGBT) of the same type but produced under different technologies were tested about the switching time-variation. This is of high importance when several IGBT are connected in series to commutate high voltage defibrillation shocks. Very often, a short voltage overload of one of the IGBT in group leads to electrical breakdown of all transistors, due to nonsynchronised driving of the gate-emitter circuits. The goal of the study was to check whether compensation of the delays introduced throughout the IGBT control circuits might be efficient despite the own dispersion of the transistor parameters.
Filtering of Chest Compression Artefacts in the Electrocardiogram	19-28
Jekova I., Krasteva V., Dotsinsky I. [ +/- abstract ][ full text ]
Long interruptions of cardiopulmonary resuscitation (CPR) in case of a sudden cardiac arrest result in higher failure rate of resuscitation. The current work concerns the filtering of the chest compression (CC) artefacts during CPR, which is essential for the CPR continuation during electrocardiogram (ECG) analysis by automated external defibrillators (AEDs). We have studied two possible approaches - one based on high-pass filter (HPF), and another using band-stop filter (BSF) with adjustable cut-off frequency. The purpose is to improve the quality of the signal provided to the ECG analysis module, aiming at a reliable decision to Stop CC if VF is present or to Continue CC for all other rhythms, including asystole (ASYS) or "normal" rhythms with ventricular complexes (NR). The two filters are tested with artificially constructed ECG+CC signals, as well as with real ECGs recorded during CPR. The HPF passes the high-frequency components of the QRS complexes and effectively suppresses CC artefacts. This allows correct recognition of NR and ASYS. However, HPF suppresses the VF amplitude thus compromising the VF detection sensitivity. The BSF is favorable for detection of NR and VF but presents problems for ASYS detection because there are often attending residual high-frequency components belonging to the CC artefacts.
Hands-off Intervals during Cardiopulmonary Resuscitation: Duration and Effect on the ECG Analysis	29-38
Krasteva V., Jekova I., Stoyanov T., Didon JP. [ +/- abstract ][ full text ]
Recent works are aimed at development of shock advisory systems (SAS) for automated external defibrillators (AEDs), which continuously analyze the electrocardiogram (ECG) during non-interrupted chest compressions (CC). Being also part of the cardiopulmonary resuscitation (CPR), small "hands-off" intervals (CC pauses) for insufflations are interrupting the CC, and thus the SAS analysis process. This study is applied on 530 CC-contaminated ECG strips taken from 168 patients who undergo out-of-hospital resuscitation interventions with AEDs. A statistical study of the short duration CC pauses is performed, showing non-normal distribution with median value of 4 seconds, quartile range between 3 and 5 seconds, min-max range between 1 and 10 seconds. Another focus is the effect of skipping the CC pauses on the SAS accuracy by supplying continuous non-linear CC-corrupted ECG signal for analysis. The SAS is tested with different coupling intervals [t1, t2], where t1 is the time before the CC pause, t2 is the time after the CC pause, t1+t2=10 seconds. The SAS accuracy on CC-corrupted linear signals [10s+0s] compared to non-linear signals [9s+1s], [8s+2s], [7s+3s], [6s+4s], [5s+5s] shows insignificant difference (p>0.05) for the different arrhythmia: ventricular fibrillation between 86% and 90.3%, normal rhythms between 88.4% and 93.5%, asystole between 80.4% and 87.3%. Several examples illustrate the performance of the SAS analysis process on various CC artefacts and ECG arrhythmias.
Utility of Different Electrocardiographical Leads during Diagnostic Ajmaline Test for Suspected Brugada Syndrome	39-54
Batchvarov V. N., Govindan M., Behr E. R. [ +/- abstract ][ full text ]
In order to compare the value of different leads and lead combinations to detect the signature Brugada type ECG pattern, we analysed digital 10-second, 15-lead ECGs (12 standard leads + leads V1 to V3 from 3rd intercostal (i.c.) space, V1h to V3h) acquired during diagnostic Ajmaline testing in 128 patients (80 men, age 37±15 years) with suspected Brugada syndrome (BS) (patient group), 15-lead resting ECGs of 108 healthy subjects (53 men, age 31.9±10.5 years) (control group A) and standard 12-lead resting ECGs of 229 healthy subjects (111 men, age 33±4 years) (control group B). Bipolar leads between V2 (positive pole) and V4 or V5 (leads V_2-4, V_2-5) were derived by subtracting leads V4 and V5 from V2 (custom-made program). The 6 peripheral, 6 right precordial leads (V1 to V3, V1h to V3h) and leads V_2-4 and V_2-5 of the patients group, leads V1h to V3h of control group A, and leads V_2-4 and V_2-5 of control group B were analysed for the presence of type 1 Brugada pattern. There were 21 (16.4%) positive and 107 (83.6%) negative Ajmaline tests. In 7 positive tests (33%), type 1 pattern appeared only in leads V1h to V3h, whereas in 14 tests 67%) it appeared in both V1 to V3 and V1h to V3h. Lead V2 displayed type 1 pattern during 10 positive tests; in all of them, plus 10 other positive tests type 1 was also noted in lead V2h (n=20, 95.2%). In all 10 cases, in which lead V2 exhibited type 1 pattern (n=10), lead V_2-4 and/or V_2-5 also exhibited type 1-like pattern. During 7 positive tests, in which lead V2h but not V2 exhibited type 1 pattern, lead V_2-4 and/or V_2-5 also demonstrated type 1 pattern. Type 1 pattern was observed in leads V3 and V3h during 1 (5%) and 5 (24%) positive tests, in 0 ECGs (0%) in control group A and in 1 ECG (0.4%) in control group B. In conclusion, the "high" V1 and V2 leads (3rd i.c. space) detect more sensitively Brugada type 1 pattern than the standard V1 and V2 leads (4th i.c. space); leads V3 and V3h are not essential for the diagnosis of BS; bipolar leads V_2-4 and V_2-5 are superior to lead V2 for the ECG diagnosis of BS.
Review on the Diagnostic Potentials of the T-loop Morphology in VCG	55-71
Bortolan G., Bressan M., Christov I. [ +/- abstract ][ full text ]
In the present work, the characterization and quantification of heterogeneous cardiac repolarization have been considered, and different studies of the authors considering particular aspects of the T-loop morphology have been reviewed. In particular, the longitudinal modifications, the age and gender influences and the diagnostic relations have been reported. The population based ECG-ILSA (Italian Longitudinal Study on Aging) database has been used in all studies. The orthogonal Frank leads were synthesized from the standard 12 lead electrocardiogram. Depending on the different studies, six to ten parameters have been obtained from the vectorcardiograms with two different methods of considering the zero point. The resulting conclusions were: 1. The modified parameters calculated towards the major axis of the T-loop proved to yield higher discriminative power. 2. The mean values of all parameters of the T-loop morphology of the healthy subjects group are statistically different from those of ischemia or myocardial infarction groups. 3. Stability of the T-loop morphology measurements made in a temporal interval of 5 years (longitudinal modifications) for one and the same patient is observed. The Angina Pectoris group characterized in general by a high "clinical instability" shows the most significant longitudinal modifications. 4. Age (< 75 years and ≥ 75 years old) and gender (male/female) have different T-loop morphology impact in the three considered groups (healthy, cardiac diseases, and hypertension). The gender influences the healthy and patients with hypertension, while age influences mainly the patients with cardiac diseases.
Ultra Low-Power Acoustic Detector Applicable in Ambient Assistance Living Systems	72-78
Iliev I. [ +/- abstract ][ full text ]
Ambient Assisted Living (AAL) includes methods, concepts, systems, devices as well as services, which provide unobtrusive support for daily life based on the context and situation of the assisted person. The technologies applied for AAL are user-centric, i.e. oriented towards the needs and capabilities of the particular user. They are also integrated into the immediate personal environment of the user. As a consequence, the technology is adapting to the user rather than the other way around. The in-house monitoring of elderly or disabled people (hard of hearing, deaf, with limited movement ability), using intelligent sensors is a very desirable service that may potentially increase the user"s autonomy and independence while minimizing the risks of living alone. The described ultra low-power acoustic detector allows upgrade of the presented warning systems. It features long-term autonomy and possibility to use it as an element of the wireless personal area network (WPAN).
EEG Spectral Analysis in Serious Gaming: An Ad Hoc Experimental Application	79-88
Minchev Z., Dukov G., Georgiev S. [ +/- abstract ][ full text ]
The application of serious gaming technology in different areas of human knowledge for learning is raising the question of quantitative measurement of the training process quality. In the present paper a pilot study of 10 healthy volunteers" EEG spectra is performed for ad hoc selected game events ("win" and "lose") via continuous wavelet transform (real and complex) on the basis of the Morlet mother wavelet function and S-transformation. The results have shown a general decrease of the alpha rhythms power spectra frequencies for the "lose" events and increase for the "win" events. This fact corresponds to an opposite behaviour of the theta rhythm of the players for the same "win" and "lose" events. Additionally, the frequency changes in the alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz) and theta2 rhythms (6-8 Hz) were supposed to be a phenomena related to positive and negative emotions appearance in the EEG activity of the players regarding the selected "win" and "lose" states.
Preliminary Results оf Assessment of Systolic and Diastolic Function in Patients with Cardiac Syndrome X Using SPECT CT	89-96
Tsonev Sv., Donova T., Garcheva M., Matveev M. [ +/- abstract ][ full text ]
The Cardiac syndrome X includes patients, mainly women, with the triad of angina pectoris, a positive exercise electrocardiogram for myocardial ischemia and angiographically smooth coronary arteries. The most common manifested clinical symptom in those patients is chest pain. In most cases, the syndrome is associated with debilitating symptomology, increased psychological morbidity and a poor quality of life. All the heterogeneity of the syndrome makes the treatment approaches to those patients unclear and uncertain.
Analysis and Modelling Excitability of Biological Structures
Corticomuscular Coherence with Low-Level Forces	97-108
Chakarov V. [ +/- abstract ][ full text ]
The present study was aimed at investigating the corticomuscular synchronization in beta- (15-30 Hz) and gamma-range (30-45 Hz) during isometric compensation of low-level forces. It is still unknown to what extent the synchronization processes in these frequency ranges can coexist or influence each other when the static component only is modulated in a dynamic stimulation pattern. We investigated the corticomuscular coherence (CMC), as well as the cortical spectral power (SP) during a visuomotor task, where 8%, 16% and 24% of the maximal voluntary contraction (MVC) were used. Seven healthy right-handed female subjects compensated isometrically the different dynamic forces with their right index finger. EEG was recorded from 52 scalp positions and belly-tendon bipolar EMG from the first dorsal interosseus muscle (FDI). Under the three conditions investigated, the beta- and gamma-range CMC existed in parallel. They behaved in a different manner: while the beta-range coherence increased linearly during higher force application, the gamma-range CMC was not significantly modulated by the force levels. Our results suggest that although gamma-range CMC is functionally associated to the isometric compensation of dynamic forces, broad beta-range CMC can fulfill functions of motor control simultaneously different when low-level forces are applied.
Prediction of Tetanic Force of Muscle Motor Units Evoked by Irregular Stimulation Patterns	109-118
Rusev R., Raikova R., Celichowski J. [ +/- abstract ][ full text ]
The aim of the paper is to propose an approach for prediction of tetanic force of different motor units (MUs) knowing the stimulation pattern. Tetanic force curves obtained by electrophysiological experiments on 13 MUs of a rat muscle were processed. They were decomposed into a series of twitches using two own-made algorithms. The parameters of the decomposed twitches were correlated with interpulse intervals (IPIs) and the level of the force at which the successive contraction begins, i.e. MinTet. Using regression equations for prediction of these parameters, the same tetanic curves and others of the same MU, but with different stimulation patterns, were reconstructed. The reconstructed curves resembled the experimental ones much better than these obtained by summation of equal twitches with the respective stimulation patterns. It was concluded that the best predictor is MinTet. In order to obtain the same prediction approach for all MUs, for arbitrary stimulation pattern, a proper normalization has to be obtained.
Eccentric Contraction-Induced Muscle Fibre Adaptation	119-126
Dimitrov V. G., Arabadzhiev T. I., Dimitrova N. A., Dimitrov G. V. [ +/- abstract ][ full text ]
Hard-strength training induces strength increasing and muscle damage, especially after eccentric contractions. Eccentric contractions also lead to muscle adaptation. Symptoms of damage after repeated bout of the same or similar eccentrically biased exercises are markedly reduced. The mechanism of this repeated bout effect is unknown. Since electromyographic (EMG) power spectra scale to lower frequencies, the adaptation is related to neural adaptation of the central nervous system (CNS) presuming activation of slow-non-fatigable motor units or synchronization of motor unit firing. However, the repeated bout effect is also observed under repeated stimulation, i.e. without participation of the CNS. The aim of this study was to compare the possible effects of changes in intracellular action potential shape and in synchronization of motor units firing on EMG power spectra. To estimate possible degree of the effects of central and peripheral changes, interferent EMG was simulated under different intracellular action potential shapes and different degrees of synchronization of motor unit firing. It was shown that the effect of changes in intracellular action potential shape and muscle fibre propagation velocity (i.e. peripheral factors) on spectral characteristics of EMG signals could be stronger than the effect of synchronization of firing of different motor units (i.e. central factors).
QSAR and Molecular Modelling
Quasi-Stationary Approximation of a Dynamical Model of microRNA Target Regulation. Part I. Establishment of Time Hierarchy in the Model Dynamics	127-134
Nikolova E., Herwig R., Petrov V. [ +/- abstract ][ full text ]
The Quasi-Steady-State Approximation (QSSA) theorem is considered as a basic approach for reduction of dimensionality of a dynamical model of microRNA target regulation. On the basis of previously determined parameters, seven ordinary differential equations of the model are written in a form appropriate to evaluate their terms for further reduction. In accordance with the terminology of the QSSA theorem, it is established that five of the system components are fast varying such that the corresponding kinetic equations form an attached system. The other two variables are slow varying and their kinetic equations form a degenerate system.
Quasi-Stationary Approximation of a Dynamical Model of MicroRNA Target Regulation. Part II. Application of the QSSA Theorem	135-142
Nikolova E., Herwig R., Petrov V. [ +/- abstract ][ full text ]
The QSSA theorem is applied to the dynamical model of microRNA target regulation after special selection of model variables, presented in Part I of this article. On the basis of this theorem the complete model, represented as a system of seven nonlinear ordinary differential equations, is reduced to a degenerate one, comprising only two ordinary differential equations. As a result it is proved that the proteins, produced by miRNAs are identified to play a driving role of the dynamical behaviour of the genetic process investigated, but in post-initial (or quasi-stationary) stage.
AMMOS: A Software Platform to Assist in silico Screening	143-150
Pencheva T., Lagorce D., Pajeva I., Villoutreix B. O., Miteva M. A. [ +/- abstract ][ full text ]
Three software packages based on the common platform of AMMOS (Automated Molecular Mechanics Optimization tool for in silico Screening) for assisting virtual ligand screening purposes have been recently developed. DG-AMMOS allows generation of 3D conformations of small molecules using distance geometry and molecular mechanics optimization. AMMOS_SmallMol is a package for structural refinement of compound collections that can be used prior to docking experiments. AMMOS_ProtLig is a package for energy minimization of protein-ligand complexes. It performs an automatic procedure for molecular mechanics minimization at different levels of flexibility - from rigid to fully flexible structures of both the ligand and the receptor. The packages have been tested on small molecules with a high structural diversity and proteins binding sites of completely different geometries and physicochemical properties. The platform is developed as an open source software and can be used in a broad range of in silico drug design studies.
The use of Computational Methods for the Assessment of Chemicals in REACH	151-162
Tsakovska I., Worth A. [ +/- abstract ][ full text ]
This article provides an overview of the use of computational methods in chemicals hazard and risk assessment under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation. The key aspects of the REACH guidance on the assessment of chemicals are discussed that treat the possible stepwise (tiered) approach combining multiple computational methods in assessing chemicals. Several publicly accessible software tools for the computer-based estimation of chemical hazard, developed by the European Commission"s Joint Research Centre (JRC), are described.
Modelling and Optimization of Bioprocess Systems
Modified Multi-Population Genetic Algorithm for Yeast Fed-batch Cultivation Parameter Identification	163-172
Angelova M., Tzonkov St., Pencheva T. [ +/- abstract ][ full text ]
In this work, a modified multi-population genetic algorithm is developed for the purpose of parameter identification of fermentation process model. Modified multi-population genetic algorithm is similar to the multi-population one and its development is instigated by modified genetic algorithm, similar to simple one. A comparison of four types of genetic algorithms, namely simple, modified, multipopulation and modified multi-population is presented for parameter identification of a fed-batch cultivation of Saccharomyces cerevisiae.
Multiple Objective Optimization of a Mass Transfer in Stirred Tank Bioreactors	173-184
Petrov M., Tzonkov St. [ +/- abstract ][ full text ]
In the present study we used the concept of Pareto for solving multiple objective optimisation of the mass transfer in a stirred tank bioreactor. The model of the mass transfer is formulated as a general multiple objective optimization problem. By using an assigned membership function for each of the objectives, the general multiple objective optimization problem can be converted into a maximizing decision problem. In order to obtain a global solution, a Price method is introduced to solve the maximizing decision problem. The policy consists of constructive and regime bioreactor parameters. After this multiple optimization, the performance of the mass transfer, aeration and mixing are improved.
Equivalent Models and Sliding Mode Stabilization of Cultivation Processes	185-196
Pavlov Y. [ +/- abstract ][ full text ]
In the paper a control design and stabilization of cultivation processes is presented. The control is based on an enlarged Wang-Monod-Yerusalimsky kinetic model and their restricted Monod-Wang and Monod forms.
Mathematical Modeling of the Process for Microbial Production of Branched Chained Amino Acids	197-210
Georgiev T., Todorov K., Ratkov A. [ +/- abstract ][ full text ]
This article deals with modelling of branched chained amino acids production. One of important branched chained amino acid is L-valine. The aim of the article is synthesis of dynamic unstructured model of fed-batch fermentation process with intensive droppings for L-valine production. The presented approach of the investigation includes the following main procedures: description of the process by generalized stoichiometric equations; preliminary data processing and calculation of specific rates for main kinetic variables; identification of the specific rates takes into account the dissolved oxygen tension; establishment and optimisation of dynamic model of the process; simulation researches. MATLAB is used as a research environment.
Influence of Polymer Substratum onto Arthobacter Oxydans 1388 Biofilm Formation	211-220
Yotova L., Marinkova D., Mironova V., Ivanov T. [ +/- abstract ][ full text ]
Microorganisms attach to surfaces and develop biofilms. Biofilm-associated cells can be differentiated from their suspended counterparts by generation of an extracellular polymeric substance (EPS) matrix, reduced growth rates, and the up- and down- regulation of specific genes. Attachment is a complex process regulated by diverse characteristics of the growth medium, substratum, and cell surface. Biofilms have great importance for public health because of their role in certain infectious diseases and importance in a variety of device-related infections. Biofilms are composed primarily of microbial cells and EPS. EPS may account for 50% to 90% of the total organic carbon of biofilms and can be considered the primary matrix material of the biofilm. EPS may vary in chemical and physical properties, but it is primarily composed of polysaccharides. Extracellular polymeric substances (EPS) are biopolymers of microbial origin in which biofilm microorganisms are embedded. Exopolysaccharides and proteins are one of the main factors in biofilm formation, evidence for microenviromental changes of microbial cells. The aim of this study was to investigate the formation, growth and biofilm characteristics from strain Arthrobacter oxydans 1388 onto different kinds of polymer matrixes and biochemical research of EPS production. It was compared three different kinds of polymer matrixes and their influence onto biofilm formation. Matrixes were obtained on the base of copolymer of acrylonitrile with acrylamide and mixed with cellulose acetate butyrate. In this case they were with high mechanical stability. The obtained results demonstrated that the most appropriate carrier for biofilm formation is the polymer matrix on the base of copolymer of acrylonitrile with acrylamide and mixed with cellulose acetate butyrate.
Immobilization of Trichosporon cutaneum R 57 Cells onto Methylcellulose/SiO₂ Hybrids and Biosorption of Cadmium and Copper Ions	221-230
Rangelova N., Georgieva N., Peshev D., Yotova L., Nenkova S. [ +/- abstract ][ full text ]
Methylcellulose/Silica (MC/SiO₂) hybrids were synthesized via poly step sol-gel method. SiO₂ was included into the hybrids from two silica precursors - methyltriethoxysilane (MTES) and ethyltrimethoxysilane (ETMS) with different quantity of organic part-5, 20 and 50 wt.%. The filamentous yeasts Trichosporon cutaneum strain R 57 was immobilized onto the synthesized MC/SiO2 hybrids. After immobilization the hybrid materials were used in the processes of sorption of cadmium and copper ions. The obtained results of protein content analysis indicated that the amount of protein increased with increasing of MC in the hybrids. It was established that the maximal efficiency of copper and cadmium removal were observed for hybrid materials containing MTES and 50 wt.% MC - 66% and 26% respectively. For ETMS and 50 wt.% MC a high value of copper removal was 56% and for cadmium - 45% removal, respectively. FTIR analysis of free and immobilized cells with metal ions was conducted. SEM images showed successful immobilization of the yeasts cells. Second order model was employed in order to investigate the kinetics of copper and cadmium biosorption.
Species Content and Distribution of the Macrozoobenthos along Rilska River, South-West Bulgaria	231-238
Moskova G., Uzunov Y., Yaneva I., Stoichev St., Vidinova Y., Tyufekchieva V., Kenderov L. [ +/- abstract ][ full text ]
Rilska River is one of the left tributaries of Struma River and it is a substantial source of drinking water for the capital city of Sofia. In spite of that the hydrobiological data are quite poor, especially these concerning bottom invertebrate fauna. This study presents the results from research on the macrozoobenthos species composition carried out in 2007-2008 at six sites along the river. During the study period totally 192 benthic taxa were found. The relatively high taxa richness and the presence of species sensitive to pollution at all investigated sites are indicative of stable low-saprobic conditions in the river. It was determined that the species composition along the river continuum differed significantly in the upper and lower part of the river and a tendency of increasing species richness downstream the river was observed.
Risk Assessment at the Beginning and the End of Strouma River in Bulgaria Using Integral Indices	239-248
Diadovski I., Atanassova M., Simeonov V. [ +/- abstract ][ full text ]
The present work considers Strouma River on the Bulgarian territory using the integral method for evaluation of climatic and anthropogenic impacts on the average annual water volume and maximum and minimum water flow. The level of this impact and risk assessment is determined by the index M_max,i for the deviation of the maximum water flow from the maximum flow norm Q_max,0 and the index M_min,i for the deviation of the minimum water flow from the minimum flow norm Q_min,0. Using the dynamics of the integral indices M_max,i, M_min,i and information on extreme events from the past, a preliminary risk assessment of future extreme events such as floods and draughts could be made. This is done for the first time in risk assessment of extreme events and has been checked at Pernik (in the beginning) and Marino pole (at the border in Greece) for the period 1948 - 2006.
Model for Quantitative Evaluation of Enzyme Replacement Treatment	249-256
Radeva B. [ +/- abstract ][ full text ]
Gaucher disease is the most frequent lysosomal disorder. Its enzyme replacement treatment was the new progress of modern biotechnology, successfully used in the last years. The evaluation of optimal dose of each patient is important due to health and economical reasons. The enzyme replacement is the most expensive treatment. It must be held continuously and without interruption. Since 2001, the enzyme replacement therapy with Cerezyme*Genzyme was formally introduced in Bulgaria, but after some time it was interrupted for 1-2 months. The dose of the patients was not optimal. The aim of our work is to find a mathematical model for quantitative evaluation of ERT of Gaucher disease. The model applies a kind of software called "Statistika 6" via the input of the individual data of 5-year-old children having the Gaucher disease treated with Cerezyme. The output results of the model gave possibilities for quantitative evaluation of the individual trends in the development of the disease of each child and its correlation. On the basis of this results, we might recommend suitable changes in ERT.
Biomedical Informatics
Modelling of a Roulette Wheel Selection Operator in Genetic Algorithms Using Generalized Nets	257-264
Pencheva T., Atanassov K., Shannon A. [ +/- abstract ][ full text ]
The apparatus of Generalized Nets (GN) is applied here to a description of a selection operator, which is one of the basic genetic algorithm operators. The GN model presented here describes roulette wheel selection. The resulting GN model could be considered as a separate module, but it can also be accumulated into a GN model to describe a whole genetic algorithm.
Application of K-Nearest Neighbor Rule in the Case of Intuitionistic Fuzzy Sets for Pattern Recognition	265-270
Todorova L., Vassilev P. [ +/- abstract ][ full text ]
In the present paper an algorithm based on the k-nearest neighbors (KNN) rule modified for the case of intuitionistic fuzziness is proposed. The algorithm calculates the degrees of membership, non-membership and indeterminacy for each new element that needs to be classified. The choice of the KNN rule is due to the high precision of the method in decision making for pattern recognition problems, while the apparatus of the intuitionistic fuzzy sets is used to describe more adequately the considered objects and allows for pattern recognition with non-strict membership of the patterns.
Ant Colony Optimization for Multiple Knapsack Problems with Controlled Starts	271-280
Fidanova S., Atanassov K., Marinov P., Parvathi R. [ +/- abstract ][ full text ]
Ant Colony Optimization is a stochastic search method that mimics the social behaviour of real ant colonies, which manage to establish the shortest routes to feeding sources and backwards. Such algorithms have been developed to reach near-optimum solutions of large-scale optimization problems, for which traditional mathematical techniques may fail. In this paper, a generalized net model of the process of ant colony optimization is constructed and on each iteration intuitionistic fuzzy estimations of the ants" start nodes are made. Several start strategies are developed and combined. This new technique is tested on Multiple Knapsack Problem, which is a real world problem. Benchmark comparisons among the strategies are presented in terms of quality of the results. Based on this comparison analysis, the performance of the algorithm is discussed along with some guidelines for determining the best strategy. The study presents ideas that should be beneficial to both practitioners and researchers involved in solving optimization problems.
Generalized Net Model of the Knowledge Discovery in Medical Databases	281-288
Orozova D., Sotirova E., Chountas P. [ +/- abstract ][ full text ]
A generalized net model has been developed of the process of discovery of hidden knowledge patterns in databases, which defines the necessary consequence of activities in order to extract knowledge from the input data. The suggested approach is applied to systems for storage and processing of medical data.