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Biomedical subjects

I P Smirnov

Publications and source records attributed to I P Smirnov.

At least 19 recordsLinked to original sources
PubMed2005

Chaos-induced intensification of wave scattering.

Sound-wave propagation in a strongly idealized model of the deep-water acoustic waveguide with a periodic range dependence is considered. It is investigated how the phenomenon of ray and wave chaos affects the sound scattering at a strong mesoscale inhomogeneity of the refractive index caused by the synoptic eddy. Methods derived in the theory of dynamical and quantum chaos are applied. When studying the properties of wave chaos we decompose the wave field into a sum of Floquet modes analogous to quantum states with fixed quasi-energies. It is demonstrated numerically that the "stable islands" from the phase portrait of the ray system reveal themselves in the coarse-grained Wigner functions of individual Floquet modes. A perturbation theory has been derived which gives an insight into the role of the mode-medium resonance in the formation of Floquet modes. It is shown that the presence of a weak internal-wave-induced perturbation giving rise to ray and wave chaos strongly increases the sensitivity of the monochromatic wave field to an appearance of the eddy. To investigate the sensitivity of the transient wave field we have considered variations of the ray travel times--arrival times of sound pulses coming to the receiver through individual ray paths--caused by the eddy. It turns out that even under conditions of ray chaos these variations are relatively predictable. This result suggests that the influence of chaotic-ray motion may be partially suppressed by using pulse signals. However, the relative predictability of travel time variations caused by a large-scale inhomogeneity is not a general property of the ray chaos. This statement is illustrated numerically by considering an inhomogeneity in the form of a perfectly reflecting bar.

Journal Article↗
PubMed2004

Suppression of alpha-cyano-4-hydroxycinnamic acid matrix clusters and reduction of chemical noise in MALDI-TOF mass spectrometry.

Progress in high-throughput MALDI-TOFMS analysis, especially in proteome applications, requires development of practical and efficient procedures for the preparation of proteins and peptides in a form suitable for high acquisition rates. These methods should improve successful identification of peptides, which depends on the signal intensity and the absence of interfering signals. Contamination of MALDI samples with alkali salts results in reduced MALDI peptide sensitivity and causes matrix cluster formation (widely reported for CHCA matrix) observed as signals dominating in the range below m/z 1200 in MALDI spectra. One way to remove these background signals, especially for concentrations of peptides lower than 10 fmol/microL, is to wash matrix/sample spots after peptide cocrystallization on the MALDI plate with deionized water prior to analysis. This method takes advantage of the low water solubility of the CHCA compared to its alkali salts. We report here that the application of some ammonium salt solutions, such as citrates and phosphates, instead of deionized water greatly improves the efficiency of this washing approach. Another way to reduce matrix cluster formation is to add ammonium salts as a part of the MALDI matrix. The best results were obtained with monoammonium phosphate, which successfully suppressed matrix clusters and improved sensitivity. Combining both of these approaches-the addition of ammonium salts in the CHCA matrix followed by one postcrystallization washing step with ammonium buffer-provided a substantial ( approximately 3-5-fold) improvement in the sensitivity of MALDI-MS detection compared to unwashed sample spots. This sample preparation method resulted in improved spectral quality and was essential for successful database searching for subnanomolar concentrations of protein digests.

Journal Article↗
PubMed2004

Wave chaos and mode-medium resonances at long-range sound propagation in the ocean.

We study how the chaotic ray motion manifests itself at a finite wavelength at long-range sound propagation in the ocean. The problem is investigated using a model of an underwater acoustic waveguide with a periodic range dependence. It is assumed that the sound propagation is governed by the parabolic equation, similar to the Schrodinger equation. When investigating the sound energy distribution in the time-depth plane, it has been found that the coexistence of chaotic and regular rays can cause a "focusing" of acoustic energy within a small temporal interval. It has been shown that this effect is a manifestation of the so-called stickiness, that is, the presence of such parts of the chaotic trajectory where the latter exhibit an almost regular behavior. Another issue considered in this paper is the range variation of the modal structure of the wave field. In a numerical simulation, it has been shown that the energy distribution over normal modes exhibits surprising periodicity. This occurs even for a mode formed by contributions from predominantly chaotic rays. The phenomenon is interpreted from the viewpoint of mode-medium resonance. For some modes, the following effect has been observed. Although an initially excited mode due to scattering at the inhomogeneity breaks up into a group of modes its amplitude at some range points almost restores the starting value. At these ranges, almost all acoustic energy gathers again in the initial mode and the coarse-grained Wigner function concentrates within a comparatively small area of the phase plane.

Journal Article↗
PubMed2001

Theory and applications of ray chaos to underwater acoustics.

Chaotic ray dynamics in deep sea propagation models is considered using the approaches developed in the theory of dynamical chaos. It has been demonstrated that the mechanism of emergence of ray chaos due to overlapping of nonlinear ray-medium resonances should play an important role in long range sound propagation. Analytical estimations, supported by numerical simulations, show that for realistic values of spatial periods and sound speed fluctuation amplitudes associated with internal-wave-induced perturbations, the resonance overlapping causes stochastic instability of ray paths. The influence of the form of the smooth unperturbed sound speed profile on ray sensitivity to the perturbation is studied. Stability analysis has been conducted by constructing the Poincaré maps and examining depth differences of ray trajectories with close take-off angles. The properties of ray travel times, including fractal properties of the time front fine structures, under condition of ray chaos have been investigated. It has been shown that the coexistence of chaotic and regular rays, typical for dynamical chaos, leads to the appearance of gaps in ray travel time distributions, which are absent in unperturbed waveguides. This phenomenon has a prototype in theory of dynamical chaos called the stochastic particle acceleration. It has been shown that mesoscale inhomogeneities with greater spatial scales than that of internal waves, create irregular local waveguide channels in the vicinity of the axis (i.e., sound speed minimum) of the unperturbed waveguide. Near-axial rays propagating at small grazing angles, "jump" irregularly between these microchannels. This mechanism determines chaotic behavior of the near-axial rays.

Journal Article↗
PubMed2001

Application of DNA-binding polymers for preparation of DNA for analysis by matrix-assisted laser desorption/ionization mass spectrometry.

The susceptibility of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to the presence of salts in a sample, especially salts of alkali metals, requires careful and often tedious desalting procedures which complicate and slow the throughput of MS-based methods. A novel approach to sample preparation was developed based on the extraction of DNA out of solution onto a solid surface with an attached DNA-binding polymer, such as polyethyleneimine or polyvinylpyrrolidone. The observed binding is strong enough to sustain washing, and, as a result, desalting and concentration can be performed in a single fast step. After DNA has been immobilized on the surface and supernatant solution removed, subsequent addition of MALDI matrix releases material from the surface, which co-crystallizes with matrix. The mass spectrometric analysis is then performed directly from this support. Analysis of oligonucleotides and three-fold multiplexed SNP typing reactions performed by this method shows improved sensitivity and excellent resolution for various DNA fragments, together with high tolerance to various buffer components, such as alkali metals and surfactants. Simplicity and speed make it attractive for high-throughput sample preparation and analysis of oligonucleotide mixtures by MALDI-MS.

Base Sequence↗
PubMed1998

[Role of thrombolytic therapy in the treatment of patients with unstable angina].

Thrombolytic therapy (TT) was performed in 39 of 81 patients with unstable angina pectoris (UAP) resistant to conventional treatment. TT was found to improve prognosis of UAP, to quicken UAP stabilization. Predictors of UAP unfavorable course were discovered. TT is indicated in patients suffering from resistant UAP with markers of poor prognosis.

Adult↗
PubMed1997

Multiplex genotyping of PCR products with MassTag-labeled primers.

A simple mass spectrometric based assay, the PinPoint assay, has previously been described for typing single nucleotide polymorphisms. The identity of a polymorphism is determined by mass differences of single base extended genotyping primers as determined by MALDI-TOF mass spectrometry. A simple method for multiplexing the assay is described, employing multiple primers with 5'oligo(dT) sequences (MassTags) which serve to mass discriminate the peaks of multiple extended and non-extended primers. The assay is extremely rapid and requires no labeling reagents.

DNA Primers↗
PubMed1997

Single-nucleotide polymorphism identification assays using a thermostable DNA polymerase and delayed extraction MALDI-TOF mass spectrometry.

We report a simple method, the PinPoint assay, for detecting and identifying single-base variations (polymorphisms) at specific locations within DNA sequences. An oligonucleotide primer is annealed to the target DNA immediately upstream of the polymorphic site and is extended by a single base in the presence of all four dideoxynucleotide triphosphates and a thermostable DNA polymerase. The extension products are desalted, concentrated, and subjected to delayed-extraction MALDI-TOF mass spectrometry. The base at the polymorphic site is identified by the mass added onto the primer. Heterozygous targets produce two mass-resolved species that represent the addition of both bases complementary to those at the polymorphic site. The assay is suitable for double-stranded PCR products without purification or strand separation. More than one primer can be simultaneously extended and then mass-analyzed. The mass spectrometric method thus shows promise for high-volume diagnostic or genotyping applications.

BRCA1 Protein↗
PubMed1996

Sequencing oligonucleotides by exonuclease digestion and delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

A protocol was developed for sequencing oligonucleotides by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Oligonucleotides were partially hydrolyzed in separate time-course digestions with 3' --> 5' and 5' --> 3' acting phosphodiesterases in a MALDI-compatible buffer or in the MALDI matrix itself. The partial digests were analyzed by MALDI-TOF mass spectrometry employing an instrument equipped with delayed ion extraction and the sequence was inferred from the mass differences between adjacent peaks. Resolution, mass accuracy, and sensitivity were considerably enhanced with delayed extraction, in comparison with the standard MALDI technique. Much longer lengths of DNA can be unambiguously sequenced with delayed extraction MALDI compared with standard MALDI-MS.

Base Sequence↗
PubMed1996

DNA sequencing by delayed extraction-matrix-assisted laser desorption/ionization time of flight mass spectrometry.

Matrix-assisted laser desorption/ionization (MALDI) time of flight mass spectrometry was used to detect and order DNA fragments generated by Sanger dideoxy cycle sequencing. This was accomplished by improving the sensitivity and resolution of the MALDI method using a delayed ion extraction technique (DE-MALDI). The cycle sequencing chemistry was optimized to produce as much as 100 fmol of each specific dideoxy terminated fragment, generated from extension of a 13-base primer annealed on 40- and 50-base templates. Analysis of the resultant sequencing mixture by DE-MALDI identified the appropriate termination products. The technique provides a new non-gel-based method to sequence DNA which may ultimately have considerable speed advantages over traditional methodologies.

Base Sequence↗
PubMed1996

Applications of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry to oligonucleotide analysis.

A delayed ion extraction technique is shown to dramatically improve mass resolution and the overall quality of matrix-assisted laser desorption ionization (MALDI) mass spectra of oligonucleotides. Isotope limited mass resolution was obtained on samples up to 10-kDa molecular mass in linear mode, and as high as 7500 mass resolution (defined at half peak height) was observed in reflector mode. This performance is as good as that achieved to date for peptides and proteins. Applications included the detection of oxidized byproducts of phosphorothioate DNA and separation of components differing only by 15 Da at 9.5-kDa molecular mass. In addition to single components, complex mixtures could also be analyzed at greatly improved performance over conventional MALDI. An example is shown for sequence verification of an oligonucleotide of 31 bases in length by analyzing the failure products. Mass accuracy was adequate to verify sequences of oligodeoxyribonucleotides up to 9500-Da molecular mass. Fast fragmentation taking place between the ionizing pulse and the extraction pulse is demonstrated to be a sequencing tool for small oligonucleotides. By proper selection of matrix material, wavelength, and irradiance, fast fragmentation can be promoted efficiently. Fragment ions tend to form from cleavage of phosphodiester bonds, as previously observed in infrared MALDI.

Base Sequence↗
PubMed1996

DNA sequence analysis by matrix-assisted laser desorption ionization MS.

The major advantage of this procedure is that, as detailed in Figure 5, the entire sequence of an oligonucleotide is determined in less than 1 h using inexpensive reagents. DE MS, because of its significantly higher resolving power, permits analysis of oligonucleotides as long as 50 bases, about twice as long as that which is possible without DE. Phosphorothioates can be sequenced after oxidation to the phosphodiester state. We have also found that the enzymes will digest through a number of modifying and protecting groups on DNA and RNA, including 2'-amino- and 2'-alkyl-substituted hydroxy groups. The resultant spectra can confirm not only the presence, but also the position, of modifying groups on both DNA and RNA molecules.

Automation↗
PubMed1995

[An atypical course of chlamydial infection].

In Burdenko Main Military Clinical Hospital 113 patients with acute lung inflammations were examined. According to the data of serological tests with application of indirect immunofluorescent reaction an antibody titer (Chlamydia Pneumoniae) was disclosed in 9 patients (11% from the whole number of 82 patients). By the authors' opinion bizarre and severe course of Chlamydia Pneumoniae could take place, thus, it is necessary to conduct serological examinations not only during epidemic outbreaks of acute respiratory diseases or pneumonias, but also during single cases of steady and long-term febrile diseases or protracted pulmonary inflammations.

Acute Disease↗
PubMed1993

[Compounds, similar to acyclovir. VIII. Synthesis and antiviral activity of (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of nucleic bases].

The (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of the uracil, thymidine, cytosine, adenine, guanine and 1,2,4-triazol-3-carboxamide were synthesized using 1,3-diacetoxy-2-(1-acetoxy)propane and 1,3-dichloro-2-(1-chlorethoxy)propane as alkylating agents. The guanine derivatives exhibited activity against HSV-1 (chemotherapeutic index 32).

Acyclovir↗
PubMed1990

[Compounds similar to acyclovir. VII. Attempts to construct an anti-herpetic agent (6-hydroxy-2-oxa-4-hexenyl derivatives of nucleic bases].

Based on the available data on the acyclovir's mechanism of action we attempted to predict the antiherpetic activity of 6-hydroxy-2-oxahexen-4-yl derivatives of nucleic bases. In terms of this model 9-(6-hydroxy-2-oxahexen-4-yl) guanine might be active. 6-Hydroxy-2-oxahexen-4-yl derivatives of adenine, guanine, cytosine, thymine, uracil, 1,2,4-triazole-3 and 1,2,4-triazole-5-carboxamide have been synthesized and their activity against herpes virus I investigated. The guanine derivative proved to possess rather high activity (chemotherapeutical index 8).

Acyclovir↗