A. Yu. Turygin

Russian Academy of Sciences, Moscow, Moscow, Russia

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Publications (20)25.11 Total impact

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    ABSTRACT: A study is conducted of the intermittency effects in fully developed hydrodynamic turbulence. The use of bounded logarithmic-normal distributions instead of the unbounded Kolmogorov-Obukhov distribution allows for the elimination of the principle difficulties connected with the use of the unbounded distribution and to obtain good agreement with the experimental data. The nonlinear interaction of long waves and inertial pulsations may explain the characteristics of the intermittency observed. A comparison is given of results obtained by employing the bounded logarithmic-normal distribution and those obtained by employing the beta-model, the two-scale Cantor set and the Kolmogorov-Obukhov unbounded log-normal distribution. The multifractal structure of developed hydrodynamic turbulence and the effects of intermittency on the distribution of passive scalar impurities are considered and results of various intermittency models are compared.
    06/2013;
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    ABSTRACT: The biochip was constructed for simultaneous assay of total and free prostate-specific antigen, alpha-fetoprotein, cancer embryonic antigen, human chorionic gonadotropin, and neuron-specific enolase. These biochips represent an array of gel elements with covalently immobilized proteins. The major analytic characteristics of the developed method were obtained. It was shown that the results of simultaneous assay of six tumor markers in blood serum well correlated with routine measurement of each marker using enzyme immunoassay kits. This approach allowed us to reveal the hook effect of high concentrations during biochip assay, which prevents distortion of the diagnostic picture at high concentration of the analyte in the sample.
    Bulletin of Experimental Biology and Medicine 06/2009; 147(6):737-41. · 0.34 Impact Factor
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    ABSTRACT: Three-dimensional gel-based biological microchips were developed for simultaneous quantitation of total (PSAtot) and free (PSAfree) forms of the prostate-specific antigen in human serum in the “one patient, one biochip” format. A method not demanding construction of calibration curves prior to the assay was applied to quantitation of PSAtot and PSAfree. In addition to gel elements with immobilized antibodies against PSAtot and PSAfree, the biochip contains elements with immobilized PSA at different concentrations, forming an internal calibration curve. Data are processed and interpreted with the special-purpose ImaGelAssay program. The sensitivity of the assay is 0.3 ng/ml for PSAtot and 0.2 ng/ml for PSAfree. The variation coefficient for measurements with one biochip series does not exceed 10%. The correlation coefficients between the estimates obtained for human sera by the biochip assay and by conventional ELISA were 0.988 for PSAtot and 0.987 for PSAfree.
    Molecular Biology 01/2007; 41(4):665-669. · 0.64 Impact Factor
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    ABSTRACT: The optimal design of oligonucleotide microchips and efficient discrimination between perfect and mismatch duplexes strongly depend on the external transport of target DNA to the cells with immobilized probes as well as on respective association and dissociation rates at the duplex formation. In this paper we present the relevant theory for hybridization of DNA fragments with oligonucleotide probes immobilized in the cells on flat substrate. With minor modifications, our theory also is applicable to reaction-diffusion hybridization kinetics for the probes immobilized on the surface of microbeads immersed in hybridization solution. The main theoretical predictions are verified with control experiments. Besides that, we compared the characteristics of the surface and gel-based oligonucleotide microchips. The comparison was performed for the chips printed with the same pin robot, for the signals measured with the same devices and processed by the same technique, and for the same hybridization conditions. The sets of probe oligonucleotides and the concentrations of probes in respective solutions used for immobilization on each platform were identical as well. We found that, despite the slower hybridization kinetics, the fluorescence signals and mutation discrimination efficiency appeared to be higher for the gel-based microchips with respect to their surface counterparts even for the relatively short hybridization time about 0.5-1 hour. Both the divergence between signals for perfects and the difference in mutation discrimination efficiency for the counterpart platforms rapidly grow with incubation time. In particular, for hybridization during 3 h the signals for gel-based microchips surpassed their surface counterparts in 5-20 times, while the ratios of signals for perfect-mismatch pairs for gel microchips exceeded the corresponding ratios for surface microchips in 2-4 times. These effects may be attributed to the better immobilization efficiency and to the higher thermodynamic association constants for duplex formation within gel pads.
    Journal of biomolecular Structure & Dynamics 09/2006; 24(1):57-66. · 2.98 Impact Factor
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    ABSTRACT: To find single-nucleotide polymorphisms (SNPs) in the human genome, three modern technologies of molecular genetic analysis were combined: the ligase detection reaction (LDR), rolling circle amplification (RCA), and immobilized microarray of gel elements (IMAGE). SNPs were detected in target DNA by selective ligation of allele-specific nucleotides in microarrays. The ligation product was assayed in microarray gel pads by RCA. Two variants of microarray analysis were compared. One included selective ligation of short oligonu-cleotides immobilized in a microarray with subsequent amplification with a preformed circular probe (a common circle). The probe was especially designed for human genome research. The other variant employed immobilized allele-specific padlock probes, which could be circularized as a result of selective ligation. Codon 72 SNP of the human p53 gene was used as a model. RCA in microarrays proved to be a quantitative assay and, in combination with LDR, allowed efficient discrimination of alleles. The principles and prospects of LDR/RCA in microarrays are discussed.
    Molecular Biology 12/2004; 39(1):26-34. · 0.64 Impact Factor
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    ABSTRACT: Binding specificity of mutant V55C disulfide bonded dimeric lambda-Cro protein (CroVC) to double-stranded DNA (dsDNA) was studied using generic hexamer oligonucleotide microchip. The curves of dissociation of hybridized DNA in the presence and absence of CroVC were converted into the effective discriminant constants to assess the relevant thermodynamic equilibrium binding constants for dsDNA-protein complexes. Then, tiling of longer oligonucleotides with shorter oligomers was used to search for sequence motifs with the highest binding specificity similarly to sequencing by hybridization. The comparison of the deduced sequences with the known natural operator half-sites demonstrated the principal ability to discern and reconstruct the major parts of 7-mer motifs corresponding to the strongest binding of CroVC subunits. Our results show the applicability of generic microchips to the analysis of binding specificity in the case of multi-subunit DNA-binding proteins.
    Journal of biomolecular Structure & Dynamics 01/2004; 21(3):425-33. · 2.98 Impact Factor
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    ABSTRACT: The review describes the history of formation and development of the microchip technology and its role in the human genome project in Russia. The main accent was done on the three-dimensional gel-based microchips developed at the Center of Biological Microchips headed by A.D. Mirzabekov since 1988. The gel-based chips of the last generation, IMAGE chips (Immobilized Micro Array of Gel Elements), have a number of advantages over the previous models. The microchips are manufactured by photoinitiated copolymerization of gel components and immobilized molecules (DNA, proteins, and ligands). This ensures an even distribution of the immobilized probe throughout the microchip gel element with a high yield (about 50% for oligonucleotides). The use of methacrylamide as a main component of the polymerization mixture resulted in a substantial increase of gel porosity without affecting its mechanical properties and stability; this allowed one to work with the DNA fragments of up to 500 nt in length, as well as with quite large protein molecules. At present, the gel-based microchips are widely applied to solve different problems. The generic microchips containing a complete set of possible hexanucleotides are used to reveal the DNA motifs binding with different proteins and to study the DNA–protein interactions. The oligonucleotide microchips are a cheap and reliable diagnostic tool designed for mass application. Biochips have been developed for identification of the tuberculosis pathogen and its antibiotic-resistant forms; of orthopoxviruses, including the smallpox virus; of the anthrax pathogen; and chromosomal rearrangements in leukemia patients. The protein microchips can be adapted for further use in proteo-mics. Bacterial and yeast cells were also immobilized in the gel, maintaining their viability, which opens a wide potential for creating biosensors on the basis of microchips.
    Molecular Biology 12/2003; 38(1):4-13. · 0.64 Impact Factor
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    ABSTRACT: The kinetics of hybridization on the oligonucleotide microchip with gel pads is studied both theoretically and experimentally. The monitoring of kinetics was performed with the measurements of fluorescence intensity produced by the labeled target oligonucleotides. As is shown, the hybridization time depends on the stability of the formed duplexes, the concentrations of target and probe oligonucleotides, and the diffusion of target oligonucleotides in solution and gel pad. The initial stage of hybridization is determined by the flow of target oligonucleotides from solution, then, followed by the diffusive propagation with approximately constant concentration of oligonucleotides at the boundary of gel pad and, finally, by the exponential saturation. The theoretical predictions of hybridization kinetics reveal a good correspondence with the experimental results and may be used for the choice of the optimal hybridization conditions. The possible applications of kinetic hybridization curves to the discrimination problems and assessment of diffusion coefficients in gel pads are briefly discussed. Finally, we discuss the relationships between the binding kinetics and the general functioning of biomolecular microchips.
    Journal of biomolecular Structure & Dynamics 11/2003; 21(2):279-88. · 2.98 Impact Factor
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    ABSTRACT: The reproducibility of melting curves for repeated hybridizations of target DNA with generic oligonucleotide microchips is shown experimentally to depend on the character of matching between fragments of target DNA and immobilized oligonucleotides. The reproducibility of melting curves is higher for the perfect match duplexes and decreases as the number of mismatched pairs within duplexes increases. This effect was applied to the comparative analysis of complex DNA mixtures. We developed a scheme in which we can identify and discriminate between the probe oligonucleotides responsible for the distinctions between target DNA mixtures. A scheme is illustrated by comparing DNA mixtures corresponding to V-D-J genes connected with populations of mRNAs CDR3 TCR Vb (T-cell receptor beta complementarity determining region 3) from the thymus and pancreas of NOD mice. Our results demonstrate that generic microchips can be applied efficiently to the analysis of DNA mixtures.
    Journal of biomolecular Structure & Dynamics 07/2001; 18(6):813-23. · 2.98 Impact Factor
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    ABSTRACT: DNA sequencing by hybridization was carried out with a microarray of all 4(6) = 4,096 hexadeoxyribonucleotides (the generic microchip). The oligonucleotides immobilized in 100 x 100 x 20-microm polyacrylamide gel pads of the generic microchip were hybridized with fluorescently labeled ssDNA, providing perfect and mismatched duplexes. Melting curves were measured in parallel for all microchip duplexes with a fluorescence microscope equipped with CCD camera. This allowed us to discriminate the perfect duplexes formed by the oligonucleotides, which are complementary to the target DNA. The DNA sequence was reconstructed by overlapping the complementary oligonucleotide probes. We developed a data processing scheme to heighten the discrimination of perfect duplexes from mismatched ones. The procedure was united with a reconstruction of the DNA sequence. The scheme includes the proper definition of a discriminant signal, preprocessing, and the variational principle for the sequence indicator function. The effectiveness of the procedure was confirmed by sequencing, proofreading, and nucleotide polymorphism (mutation) analysis of 13 DNA fragments from 31 to 70 nucleotides long.
    Journal of biomolecular Structure & Dynamics 09/2000; 18(1):83-101. · 2.98 Impact Factor
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    V R Chechetkin, A Y Turygin
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    ABSTRACT: We present a method for unified statistical analysis of short and long range correlations between various nucleotides in genomic DNA strands. The approach is based on the mutual study of Fourier structure factor spectra and pair correlation functions. The analysis of cross correlations in the different ranges of structural spectra permits identification of the main sources of correlations, namely, the coherent point mutations, coincident periodicities or large scale density variations. The technique for assessment of structural coupling between various genes in the genome is also described.
    Journal of Theoretical Biology 02/1996; 178(2):205-17. · 2.35 Impact Factor
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    ABSTRACT: Hidden periodicities play a very important role in the regulatory and structural functioning of genomic DNA strands. Primarily, it concerns the fundamental three-periodicity inherent to protein coding regions in all taxonomic groups, two-periodicity in introns of eukaryots as well as periodicities related to helix and chromatin pitches, while the other periodicities appear to be species specific. Rather roughly (and without sharp boundary) the underlying periodicities may be divided by two groups. In the first case the periodicities are due to particular nucleotides (or very short oligomers) quasi-regularly positioned in a seemingly random background. This type of regularity can be identified via either standard frequency analysis or more elaborate Fourier methods. For the second group a periodicity is related to the quasi-random replacements in initially complete repeating motifs (situation typical, e.g., for modifications of satellites). In the last case the statistical reconstruction of underlying repeats is a much less trivial task. The authors show that this problem can successfully be solved with multi-symbol extension of energy-minimizing neural networks (EMNN). The reconstruction of underlying motifs may shed additional light on the evolutionary and functional modifications in various genomes
    Neuroinformatics and Neurocomputers, 1995., Second International Symposium on Neuroinformatics and Neurocomputers; 09/1995
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    V.R. Chechetkin, A.Yu. Turygin
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    ABSTRACT: The investigation of size-dependence for three-periodic Fourier harmonics may resolve between the model with the long-range correlations for different nucleotides and the representation of the genome in terms of a mosaic picture with uncorrelated structural units. The study indicates superstructural organization in genomic DNA sequences. The possible physical mechanisms for formation of such a structure are discussed.
    Physics Letters A 03/1995; 199(1):75-80. · 1.63 Impact Factor
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    V R Chechetkin, A Y Turygin
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    ABSTRACT: The spectral representation gives an effective approach to the analysis of statistical characteristics of symbolic sequences. We derive the corresponding criteria for the random case. The criteria ensure the dichotomic classification (random-non-random) for relatively short sequences of about several thousand symbols. The theory is applied to inflation models, symbolic dynamics and DNA sequences.
    Journal of Physics A General Physics 07/1994; 27(14):4875-4898.
  • A. Yu. Turygin, V. R. Chechetkin
    Journal of Experimental and Theoretical Physics - J EXP THEOR PHYS. 01/1994; 79:186-196.
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    ABSTRACT: We discuss intermittency effects in the distribution of scalar passive impurities within fully developed hydrodynamic turbulence. It is shown that the observable stronger intermittency effects in the distribution of passive impurities with respect to that for the energy dissipation rate can naturally be explained in the framework of composite random cascade models. We discuss doubly random bounded and unbounded log-normal models, the doubly random-model, and the two-scale Cantor set approximation. Then the problem of mutual correlations is discussed. The various results are compared with experiments.
    Journal of Statistical Physics 10/1990; 61(3):589-605. · 1.40 Impact Factor
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    ABSTRACT: We discuss intermittency effects in fully developed hydrodynamic turbulence. It is shown that the application of the bounded log-normal distribution to the fluctuations of the local energy dissipation rate resolves some basic difficulties related to Kolmogorov's third hypothesis and gives a good agreement with experiment. The nonlinear interaction of the large-scale and inertial-range turbulent pulsations of the velocities may explain the observable characteristics of the intermittency. We give also a detailed comparison of the results obtained with the use of the bounded log-normal distribution with that obtained in the framework of the homogeneous and random-models, a two-scale Cantor set approximation, and the original unbounded log-normal distribution suggested by Kolmogorov and Obukhov.
    Journal of Statistical Physics 10/1990; 61(3):573-588. · 1.40 Impact Factor
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    ABSTRACT: Theory based on the minimum propagating zone (MPZ) criterion overestimates the critical heat of quench in partially stabilized superconducting magnets. The discrepancy is especially important for high values of the Stekly parameter. In this paper the variational principle for the calculation of critical heat of quench is discussed and the results obtained using this principle are compared with those based on the MPZ theory and obtained by direct dynamic numerical simulations. It is shown that the variational calculations can effectively be used for determination of critical heat.
    Cryogenics 01/1990; 30(1):32-36. · 1.17 Impact Factor
  • Soviet Physics Doklady. 09/1989;
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Publication Stats

137 Citations
25.11 Total Impact Points

Institutions

  • 2000–2007
    • Russian Academy of Sciences
      • Engelhardt Institute of Molecular Biology
      Moscow, Moscow, Russia
  • 2003–2004
    • Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук
      Moskva, Moscow, Russia
  • 1994–1996
    • Troitsk Institute for Innovation and Fusion Research (TRINITI)
      Troitsk, Omsk, Russia
  • 1990
    • Moscow State Institute of Radio Engineering, Electronics and Automation
      Moskva, Moscow, Russia