Biomedical subjects

A S Sergeev

Publications and source records attributed to A S Sergeev.

At least 19 recordsLinked to original sources

PubMed2006

Generation of Cherenkov superradiance pulses with a peak power exceeding the power of the driving short electron beam.

Theoretical investigation of a short electron beam (extended bunch) interaction with a backward wave propagating in a slow wave structure demonstrates the possibility of producing ultrashort superradiance pulses with a peak power which exceeds the power of the driving beam (conversion factor K>1). It is shown that a nonuniform slow wave structure with optimized profile is beneficial in order to increase the conversion factor. The results of theoretical analysis are confirmed by the experiments. At X band using the SINUS-150 accelerator (4 ns, 330 kV, 2.6 kA) 0.6-0.8 ns superradiance pulses with a peak power of 1.2 GW and a conversion factor of 1.5 were obtained. Similar experiments at Ka-band based on the RADAN-303 accelerator (1 ns, 290 kV, 2.5 kA) demonstrated production of the superradiance (SR) pulse with duration 200 ps and peak power about 1 GW (conversion factor of 1.4).

Journal Article↗

PubMed2003

[The use of discrete characters in discriminant analysis for diagnosis of pulmonary tuberculosis and for classification of patients differing in treatment efficiency based on polymorphisms at nine codominant loci-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 and ESD].

Discriminant analysis was used to differentiate patients with pulmonary tuberculosis (N = 106) from healthy individuals (N = 328) and patients whose treatment was efficient (N = 71) from those whose treatment was inefficient (N = 35). The analysis involved the data on nine polymorphic codominant loci: HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD. The loci were selected by significance of differences in genotype frequencies between tuberculosis patients and healthy controls (GC, TF, PI, C3, ACP1) or between the two groups of patients differing in treatment efficiency (HP, GC, PI, PGM1, C3, ESD). Discrimination was based on a graphic method of Bayes classification procedure with a single-variate nomograph allowing easy estimation of the a posteriori probabilities for an individual to be classified. The two groups of patients proved to be discriminated sufficiently well (probability of misclassification Perr = 0.24), whereas discrimination between tuberculosis patients and healthy individuals was less efficient (Perr = 0.33). The method was proposed as a means of predicting the efficiency of treatment in pulmonary tuberculosis. Along with clinical, roentgenological, and laboratory examination, discriminant analysis may be employed as an accessory test in diagnostics of pulmonary tuberculosis, especially when the diagnosis is questionable.

Adult↗

PubMed2002

Observation of chaotic dynamics in a powerful backward-wave oscillator.

Self-modulation regimes of generation in a powerful 10-micros X-band backward-wave oscillator were studied theoretically and experimentally. The sequence of the self-modulation patterns and corresponding bifurcation values observed as the current was increased were in good agreement with the results of simulations. It was found that at a current of 120 A chaotic self-modulation set in at a power of 2 MW and a relative spectral width of 4%.

Journal Article↗

PubMed2002

[Heterozygosity in patients with pulmonary tuberculosis showing varying responses to therapy].

The distribution of the levels of heterozygosity was analyzed by 9 loci of genetic markers: PI, TF, PGM1, ACPI, HP, GC, GLO1 C3, and ESD in two groups of patients with pulmonary tuberculosis who had improvements (Group 1, n = 71) and failures (Group 2, n = 35). The heterozygosity observed in the groups was compared with that calculated by the Hardy-Weinberg law by using data on healthy controls (n = 328; the locus ESD was investigated in 78 healthy individuals). The analysis indicated that there were statistically significant deviations of the observed heterozygosities, g1, at 4 loci (GC, PI, C3, and ACPI) from the expected ones; h1 calculated from the data in the control group. The observed heterozygisities were higher than the expected ones at 3 loci (PI, C3, and ACPI), and at the GC locus. the observed heterozygosity being lower than the expected one. Comparing the observed heterozygosities. g1, within the loci, by using Fisher's exact test revealed significant differences between the groups of patients and healthy controls at the same loci, which showed significant differences between the observed and expected heterozygosities. There were no differences between the groups of patients by the observed heterozygosities. The mean expected heterozygosity were h = 0.386 +/- 0.056. The mean observed heterozygosity, were g = 0.415 +/- 0.037, 0.402 +/- 0.061, 0.371 +/- 0.055 in Groups 1 and 2 and in the controls, respectively. There were no differences between the mean expected and obsorved heterozygosities or between the mean observed heterozygosities in the three groups under study. It is proposed that a single locus rather than the mean heterozygosities should be used as a generalized nonspecific measure of genetic control over diseases while the former can show the involvement of a specific marker locus to develop a disease, the latter can simply veil the effects of each of the loci alone. Thus, the findings produce strong evidence for that there is a genetic control in the development of pulmonary tuberculosis.

Genetic Carrier Screening↗

PubMed2002

[The use of the expectation-maximization (EM) algorithm for maximum likelihood estimation of gametic frequencies of multilocus polymorphic codominant systems based on sampled population data].

Estimation of gametic frequencies in multilocus polymorphic systems based on the numerical distribution of multilocus genotypes in a population sample ("analysis without pedigrees") is difficult because some gametes are not recognized in the data obtained. Even in the case of codominant systems, where all alleles can be recognized by genotypes, so that direct estimation of the frequencies of genes (alleles) is possible ("complete data"), estimation of the frequencies of multilocus gametes based on the data on multilocus genotypes is sometimes impossible, whether population data or even family data are used for studying genotypic segregation or analysis of linkage ("incomplete data"). Such "incomplete data" are analyzed based on the corresponding genetic models using the expectation-maximization (EM) algorithm. In this study, the EM algorithm based on the random-marriage model for a nonsubdivided population was used to estimate gametic frequencies. The EM algorithm used in the study does not set any limitations on the number of loci and the number of alleles of each locus. Locus and alleles are identified by numeration making possible to arrange loops. In each combination of alleles for a given combination of m out of L loci (L is the total number of loci studied), all alleles are assigned value 1, and the remaining alleles are assigned value 0. The sum of zeros and unities for each gamete is its gametic value (h), and the sum of the gametic values of the gametes that form a given genotype is the genotypic value (g) of this genotype. Then, gametes with the same h are united into a single class, which reduces the number of the estimated parameters. In a general case of m loci, this procedure yields m + 1 classes of gametes and 2m + 1 classes of genotypes with genotypic values g = 0, 1, 2, ..., 2m. The unknown frequencies of the m + 1 classes of gametes can be represented as functions of the gametic frequencies whose maximum likelihood estimations (MLEs) have been obtained in all previous EM procedures and the only unknown frequency (Pm(m)) that is to be estimated in the given EM procedure. At the expectation step, the expected frequencies (Fm(g) of the genotypes with genotypic values g are expressed in terms of the products of the frequencies of m + 1 classes of gametes. The data on genotypes are the numbers (ng) of individuals with genotypic values g = 0, 1, 2, 3, ..., 2m. The maximization step is the maximization of the logarithm of the likelihood function (LLF) for ng values. Thus, the EM algorithm is reduced, in each case, to solution of only one equation with one unknown parameter with the use of the ng values, i.e., the numbers of individuals after the corresponding regrouping of the data on the individuals' genotypes. Treatment of the data obtained by Kurbatova on the MNSs and Rhesus systems with alleles C, Cw, c, D, d, E, e with the use of Weir's EM algorithm and the EM algorithm suggested in this study yielded similar results. However, the MLEs of the parameters obtained with the use of either algorithm often converged to a wrong solution: the sum of the frequencies of all gametes (4 and 12 gametes for MNSs and Rhesus, respectively) was not equal to 1.0 even if the global maximum of LLF was reached for each of them (as it was for MNSs with the use of Weir's EM algorithm), with each parameter falling within admissible limits (e.g., [0, min(PN,Ps)] for PNs). The chi 2 function is suggested to be used as a goodness-of-fit function for the distribution of genotypes in a sample in order to select acceptable solutions. However, the minimum of this function only guarantee the acceptability of solutions if all limitations on the parameters are met: the sum of estimations of gametic frequencies is 1.0, each frequency falls within the admissible limits, and the "gametic algebra" is complied with (none of the frequencies is negative).

Algorithms↗

PubMed2001

[Analysis of heterozygosity levels at P1,TF, PGM1, ACP1, HP, GC, GLO, C3, and ESD loci in pulmonary tuberculosis patients with different treatment outcomes].

Heterozygosity at nine genetic loci (PI, TF, PGM1, ACP1, HP, GC, GLO1, C3, and ESD) was analyzed in pulmonary tuberculosis patients with good (group 1, N = 71) and poor (group 2, N = 35) response to treatment. The observed heterozygosities were compared with the expected values, which were calculated from allele frequencies in a control sample of healthy individuals (N = 328 with all but one locus and 78 with ESD) according to Hardy-Weinberg expectations. The analysis showed that the observed heterozygosities gl of patients significantly differed from the expected values hl in the case of four loci (GC, PI, C3, and ACP1). The observed heterozygosity was higher than expected in three cases (PI, C3, and ACP1) and lower then expected (GC) in one case. When data on each individual locus were compared using Fisher's exact test, both groups of patients proved to significantly differ (PF < 0.05) from the control group in the same four loci. No difference in observed heterozygosity was detected between the two groups of patients. The mean expected heterozygosity was h = 0.386 +/- 0.00674; the mean observed heterozygosity was g = 0.415 +/- 0.02 in group 1, g = 0.402 +/- 0.026 in group 2, and g = 0.371 +/- 0.00955 in the control group. The t test did not reveal a significant difference between the mean values of expected observed heterozygosities. Heterozygosity at individual loci, rather than mean heterozygosity, was proposed as an integral nonspecific indicator of the genetic control of a disease, because the former directly implicates individual marker loci in the development of a disorder, whereas effects of individual loci may eliminate each other when mean heterozygosity is computed. Based on the results obtained, a genetic control was assumed for the development of the tuberculosis process in the lungs.

Alleles↗

PubMed2000

[Analysis of genetic heterogeneity of bronchial asthma in relation with the age at the onset of disease].

Earlier, the distribution of bronchial asthma (BA) morbidity with respect to the age of onset (AO) in the Moscow population was found to be bimodal. The distribution had two peaks (before and after 25 years of age) and a significant (P < 0.001) minimum between them. Based on these data, genetic heterogeneity of BA with respect to AO was hypothesized. The purpose of this study was to test this hypothesis via analysis of BA morbidity in families of probands with different AOs. The BA morbidity at different ages and the total recurrent risk of BA were estimated in 1518 relatives of 815 BA probands registered in several district outpatient clinics of Moscow. Based on the data obtained, phenotypic between relatives and correlation by genotype between early-onset and late-onset BA cases (with AOs under and over 25 years, respectively) were estimated. It was demonstrated for the first time that the age distribution of BA morbidity in families of probands was also bimodal. Moreover, when probands with early and late AOs were analyzed separately, proband relatives in each of the two groups exhibited these two peaks of morbidity. This suggests that BA that begins in adolescence and BA of adults are not genetically independent forms of the disease. This agrees with the data on the correlation by genotype between the "forms" with the early and late AOs, which does not significantly differ from 1. However, the prevalence of BA was higher in relatives of those probands who developed BA under the age of 25 compared to relatives of those who developed BA over the age of 25 (11.28 and 7.31%, respectively; P < 0.05). Therefore, patients with early-onset BA are more "burdened" genetically with respect to this disease. Since the BA genetic heterogeneity connected with AO has not been confirmed in this study, it is assumed that the observed bimodal distribution of BA morbidity with respect to age is accounted for by the effect of age itself. In other words, it is hypothesized that ontogenetic factors affect susceptibility to BA so that the susceptibility threshold varies with age.

Adolescent↗

PubMed2000

[Blood protein phenotypes and effectiveness of the treatment of patients with pulmonary tuberculosis].

Genetic polymorphism at 9 independent loci (HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD) was studied in two groups of patients with pulmonary tuberculosis and healthy controls. The patients were subdivided into two subgroups depending on their response to chemotherapy: 1) responsive and 2) unresponsive to adequate chemotherapy. The control (Group 3) comprised 327-329 healthy persons; only 78 of them were phenotyped for ESD-locus. A pairwise comparison of arcsinus-transformed both phenotypic and allelic frequencies using t-test revealed significant differences between Groups 1 and 3 in phenotypes--GC 1F-1S, (P = 3.73 x 10(-4), C3 F-S (P = 4.10 x 10(-5), C3 S-S (P = 1.9 x 10(-6) and in alleles--C3*F (P = 4.2 x 10(-6), C3*S (P = 1.7 x 10(-6). These differences are reliable at the levels of significance, Pc corrected by all numbers of times, k, of independent pairwise comparisons (k = 126 for phenotypes, Pc = 0.00041; k = 60 for alleles, Pc = 0.000855). Differences between Groups 2 and 3 were significant as well: there were 8 P values both for phenotypes and alleles, which rejected the null-hypothesis at 5% significance while the expected numbers of times, kch, to reject the null-hypothesis by chance, were kch = 6.3 for phenotypes and kch = 3 for alleles. Differences between the two subgroups of patients were found to be insignificant because the P values were obtained, that rejected the null-hypothesis only 6 and 3 times for phenotypes and alleles, respectively. Principal component analysis showed that the GLO1 locus was not informative for the differences in the groups studied. The perspectives of further analysis of the data presented using the remaining 8 loci are discussed.

Adult↗

PubMed2000

[Epidemiological and immunogenetic analysis of tuberculosis and diabetes mellitus association].

The prevalence of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) among adults in two Moscow okrugs was studied. It was 0.218 and 1.678%, respectively, the latter form being encountered 7.7 times more frequently. Patients with pulmonary tuberculosis followed at tuberculosis control dispensaries (n = 69,012) were found to have diabetes mellitus in 236 cases (120 with IDDM and 116 with NIDDM). The prevalence of IDDM among the tuberculosis control dispensary patients was 1.7%, which was 8 times greater than that in the general population. That of NIDDM was 1.68%, which did not significantly differ from that in the population. Epidemiological analysis showed that there was a highly significant association of tuberculosis with diabetes mellitus in the population. The risk for IDDM was 3.6% in patients and exceeded that in the population while the risk for NIDDM in the population was the same as that in the population. Analyzing the distribution of immunogenetic HLA-1 and HLA-2 markers showed that patients with tuberculosis concurrent with IDDM were intermediate between a group of patients with isolated tuberculosis and isolated IDDM.

Adolescent↗

PubMed2000

[Calculation of the morbid risk in genetic-epidemiologic studies of age-dependent diseases].

Distributions of age at onset are widely used in the genetic epidemiology of age-dependent diseases. Examples are estimation of recurrent risks in genetic counselling and testing genetic hypotheses in segregation and linkage analyses. In this study, morbidity parameters are defined, including age-specific morbidity rates, morbidity net risk (incidence), and cumulative incidence (population risk, an integrated measure of population susceptibility to the disease at the moment of the study). Age-specific morbidity risks are calculated from the respective morbidity rates, which are analogous to mortality rates used in demography. Population data typically used for calculation of morbidity rates are discussed. Methods of calculation of morbidity rates based on the data of single and interval epidemiological studies are described. Methods for calculating standard errors of these parameters, estimating their statistical reliability, and testing statistical hypotheses are discussed.

Aging↗

PubMed1999

Generation of powerful subnanosecond microwave pulses by intense electron bunches moving in a periodic backward wave structure in the superradiative regime.

Experimental results of the observation of coherent stimulated radiation from subnanosecond electron bunches moving through a periodic waveguide and interacting with a backward propagating wave are presented. The subnanosecond microwave pulses in Ka and W bands were generated with repetition frequencies of up to 25 Hz. The mechanism of microwave pulse generation was associated with self-bunching, and the mutual influence of different parts of the electron pulse due to slippage of the wave with respect to the electrons; this can be interpreted as superradiance. The illumination of a panel of neon bulbs resulted in a finely structured pattern corresponding to the excitation of the TM01 mode. Observation of rf breakdown of ambient air, as well as direct measurements by hot-carrier germanium detectors, leads to an estimate of the absolute peak power as high as 60 MW for the 300-ps pulses at 38 GHz. These results are compared with numerical simulations. The initial observation of 75-GHz, 10-15-MW radiation pulses with a duration of less than 150 ps is also reported.

Journal Article↗

PubMed1999

Theory and design of a free-electron maser with two-dimensional feedback driven by a sheet electron beam.

The use of two-dimensional Bragg resonators of planar geometry, realizing two-dimensional (2D) distributed feedback, is considered as a method of producing spatially coherent radiation from a large sheet electron beam. The spectrum of eigenmodes is found for a 2D Bragg resonator when the sides of the resonator are open and also when they are closed. The higher selectivity of the open resonator in comparison with the closed one is shown. A time-domain analysis of the excitation of an open 2D Bragg resonator by a sheet electron beam demonstrates that a single-mode steady-state oscillation regime may be obtained for a sheet electron beam of width 100-1000 wavelengths. Nevertheless, for a free-electron maser (FEM) with a closed 2D Bragg resonator, a steady-state regime can also be realized if the beam width does not exceed 50-100 wavelengths. The parameters for a FEM with a 2D planar Bragg resonator driven by a sheet electron beam based on the U-2 accelerator (INP RAS, Novosibirsk) are estimated and the project is described.

Journal Article↗

PubMed1999

[Discriminant analysis of clinical laboratory data for diagnosis and treatment of tuberculosis and lung cancer].

The study is based on the clinical observation and examination of 33 patients with stages 1 or 2 lung cancer (Group 1), 53 with stage 3 lung cancer (Group 2), and 44 patients with pulmonary tuberculosis (Group 3). All the patients underwent surgical treatment. A control group comprised 50 apparently healthy individuals. The clinical laboratory studies included general peripheral blood analysis of ESR, the levels of hemoglobin, leukocytes, lymphocytes, total protein and albumin. ANOVA revealed a highly significant (p < 0.00004) differences in 5 of the 6 study laboratory parameters, variations in the level of total protein between the groups did not differ from that in the groups (p = 0.25). ANOVA revealed significant covariation of the levels of protein with ESR (p < 0.00004) and those of albumin (p < 0.00004). When variations in the latter were eliminated, the effect of the groups on total protein variation was highly significant (p = 0.0018). Discriminant analysis showed that the parameters studied were of diagnostic value in the differential diagnosis: probabilities of correct subdivision of patients ranged 72.6 to 78%, those of erroneous classification being 27.4 and 22%, respectively. The actual probabilities of misclassification were twofold lower. The problems in the employment of the discriminant procedure in the differential diagnosis of the study diseases using the specific contingent principle are discussed and a specific clinical observation is cited as an example.

Adult↗

PubMed1996

[Computer programs SAN and EPID: family analysis and epidemiology of multifactorial diseases].

SAN software, a database management system, is elaborated. It is subject-oriented to family analysis in the genetics of multifactorial traits (diseases). The software allows creating and maintaining a family-oriented database and using the inputted information to calculate relative risk of disease, heritability, and correlations between several diseases or forms, with both actual frequency of the trait (prevalence) and probability of new cases (incidence). If appropriate data on sibships or nuclear families are available, one can calculate an empirical estimation of the risk of repeated cases of the disease in a family in relation to family anamnesis in different methods of sampling, sex-related morbidity, and varying age of onset. The database may also be used independently as a card index. The software allows one to represent pedigrees graphically, highlighting the desired set of traits. As application program, EPID, was developed, aimed at calculation and graphical presentation of age-related estimations of prevalence and incidence, as well as of the population risk of an individual to develop a disease within a time interval from birth to a certain age (accumulated morbidity).

Causality↗

PubMed1996

[Retrospective estimation of the frequency of heterozygous beta-thalassemia in the Crimean Tartar population. Formulation of the problem. Estimation of the gametic contribution to a mixed population from frequencies of the ABO blood group genes].

Polymorphism of the beta-thalassemia gene frequency in non-indigenous populations of Central Asia, especially Crimean Tartars, is often explained by inter-ethnic marriages. The frequencies of these marriages, however, are not sufficient to produce the observed gene frequencies. Because of this, an estimation of the extent of Uzbek gametic contribution to the ethnic group of Crimean Tartar origin was conducted using data on the frequencies of ABO blood group genes. The maximum-likelihood estimate obtained (0.325) was used to determine the heterozygous beta-thalassemia frequency of the ancestral Crimean Tartar population.

ABO Blood-Group System↗

PubMed1996

[Retrospective estimation of the frequency of heterozygous beta-thalassemia in the Crimean Tatar population. Estimation of gene frequency in the ancestral population based on mixed population data with a known admixture rate].

Results of the maximum-likelihood estimation of heterozygous beta-thalassemia frequency in the Crimean Tartar ancestral population obtained by evaluating the gametic contribution of Uzbeks to the Crimean Tartar ethnic group are presented. The computing algorithm is given, and reliability of the obtained results is discussed.

Algorithms↗

PubMed1995

[Population risk of bronchial asthma occurrence in Moscow].

Age-specific prevalence and incidence of bronchial asthma (BA) were estimated in a number of districts in Moscow. The average prevalence was measured as the current proportion of BA patients registered in district outpatient clinics of both the center and periphery of Moscow (2442 patients in total) among the entire population served by to these clinics. This proportion was found to be 0.5% for both men and women. Before 25 years of age, BA appeared to be commoner in males (0.57%, versus 0.3% in females); after 40 years of age, it was commoner in females (0.89%, versus 0.47% in males). The morbidity of the disease measured as the frequency of new cases of BA (diagnosed for the first time in the given patient) had two maximums for each gender: in females, between birth and nine years of age and at 45-54 years (0.39 and 0.45%, respectively) and in males, between birth and nine years and at 55-64 years (0.75 and 0.74%, respectively); and a minimum at 20-29 years of age (0.14 and 0.05% for females and males, respectively). The majority (80%) of adult BA patients were first diagnosed with BA in adulthood. The dynamics of BA incidence appeared to differ in males and females. The male incidence changed more drastically with age, while the incidence in adult females reached a maximum 10 years earlier than in adult males. The population risk of being registered for BA (accumulated morbidity) by the age of 15, 40, and 80 was 0.98, 1.35, and 2.97%, respectively, for males and 0.58, 0.95, and 2.13%, respectively, for females.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Frequency analysis of HLA-DQA1 and HLA-DQB1 gene alleles and susceptibility to type 1 diabetes mellitus in Russian patients.

The HLA-DQA1 and DQB1 genes have recently been recognized to be strong genetic markers of susceptibility to type 1 (insulin-dependent) diabetes mellitus. The Arg52 DQA1 and non-Asp57 DQB1 alleles of these genes correlate with the disease predisposition and the Asp57 DQB1 and non-Arg52 DQA1 alleles with disease protection. We investigated 113 patients with type 1 diabetes and 121 healthy subjects from the Russian population of Moscow using DNA amplification and dot-blot hybridization with sequence-specific oligonucleotides (SSO). Using conventional statistical methods we confirmed previous observations indicating the important role of the above-mentioned amino acid residues in susceptibility and resistance to type 1 diabetes. Relative risk values for all alleles and absolute risk for carriers of most predisposing allele combinations were calculated. The absolute risk for carriers of DQA1 and DQB1 gene alleles allowing for the formation of four possible 'diabetogenic' heterodimers on the surface of immunocompetent cells, regardless of the type of coding (cis or trans), was 2.54%, which is 13 times greater than the background risk for the Russian population--0.2% up to 30 years of age.

Adolescent↗