[On the tactics of management and treatment of patients with congenital cerebral hernias in their localization in the maxillofacial region]. / O taktike vedeniya i lecheniya bol'nykh s vrozhdennymi mozgovymi gryzhami pri ikh lokalizatsii v chelyustno-litsevoi oblasti.

The analysis of the state of two patients with congenital cerebral hernias was carried out, which made it possible to establish differences in the effect of hernias on the state of the body. In the first case, the hernia is localized in the nasal cavity, and after its removal, the postoperative cerebrospinal fluid (CSF) leakage was stopped by a flap of the mucous membrane from the opposite side of the nasal septum. In the second case clinical analysis and computed tomography made it possible to state that the hernia was in the retromaxillary space and did not affect the patient's condition. Computed tomography shows signs of moderate blood pressure on the adjacent formations, and removal of the hernia and stopping the subsequent CSF leakage were impossible. The presented observations demonstrate an ambiguous approach to resolving the issue of surgical intervention in such cases.

Agent-Based Simulation of the COVID-19 Epidemic in Russia.

The COVID-19 pandemic has created a public health emergency in Russia and across the world. The wavelike spread of the new coronavirus infection, caused by newly emerging variants of the coronavirus, has led to a high incidence rate in all subjects of the Russian Federation. It is becoming extremely topical to get the opportunity to manage the development of the epidemic and assess the impact of certain regulatory measures on this process. This will help government agencies make informed decisions to control the burden on healthcare organizations. It is often impossible to obtain such assessments without using modern mathematical models.

Markov chain Monte Carlo method in Bayesian reconstruction of dynamical systems from noisy chaotic time series.

The impossibility to use the MCMC (Markov chain Monte Carlo) methods for long noisy chaotic time series (TS) (due to high computational complexity) is a serious limitation for reconstruction of dynamical systems (DSs). In particular, it does not allow one to use the universal Bayesian approach for reconstruction of a DS in the most interesting case of the unknown evolution operator of the system. We propose a technique that makes it possible to use the MCMC methods for Bayesian reconstruction of a DS from noisy chaotic TS of arbitrary long duration.

Modified Bayesian approach for the reconstruction of dynamical systems from time series.

Some recent papers were concerned with applicability of the Bayesian (statistical) approach to reconstruction of dynamic systems (DS) from experimental data. A significant merit of the approach is its universality. But, being correct in terms of meeting conditions of the underlying theorem, the Bayesian approach to reconstruction of DS is hard to realize in the most interesting case of noisy chaotic time series (TS). In this work we consider a modification of the Bayesian approach that can be used for reconstruction of DS from noisy TS. We demonstrate efficiency of the modified approach for solution of two types of problems: (1) finding values of parameters of a known DS by noisy TS; (2) classification of modes of behavior of such a DS by short TS with pronounced noise.

The properties of ion channels formed by the coumarin antibiotic, novobiocin, in lipid bilayers.

The coumarin antibiotic novobiocin forms ion channels of varying conductances in lipid bilayers. The conductances (about 20, 22, 14, 7 and 2 pS for 100 mM NH4Cl, CsCl, KCl, NaCl and LiCl, respectively) and selectivities (cation transference numbers in the range of 0.97-0.98) of one type of novobiocin-induced channel are similar to those found for channels formed by gramicidin A, an antibiotic of very different structure. The conductance of novobiocin channels of this type was independent of the species of the membrane lipid. This observation suggests that novobiocin molecules directly form these channels, and that channels are not formed through defects in lipid structure. The similarity in conductance and ion selectivity between channels induced by novobiocin and those formed by gramicidin A suggests that these structurally different molecules form channels with comparable internal diameter and internal surface charge distribution. Using HPLC purification we argue that the channel-forming activity of novobiocin is related to the activity of the novobiocin molecule itself, and not to a contaminant of the commercially available novobiocin sodium salt preparation.

The effect of sterols on the sensitivity of membranes to the channel-forming antifungal antibiotic, syringomycin E.

The ability of three sterols of different structure to influence the interaction of syringomycin E (an antifungal antibiotic that forms voltage dependent channels in planar lipid bilayers) with a planar lipid bilayer was evaluated. The rate of increase of bilayer conductance induced by syringomycin E was about 1000-times less in bilayers containing 50 mol% of cholesterol compared to bilayers without sterols. The effect of ergosterol (the primary sterol of fungal cells) on the sensitivity of bilayers to syringomycin E was much weaker than that of cholesterol, while stigmasterol (one of the main sterols of plant cells) did not significantly influence the ability of syringomycin E to induce a conductance increase in the bilayer. None of the sterols altered the single channel conductance properties of syringomycin E. These observations suggest that cholesterol affects the sensitivity of target membranes to syringomycin E by enlarging the energy barrier for channel formation rather than participating in channel formation itself.

The arginine taste receptor. Physiology, biochemistry, and immunohistochemistry.

The amino acid, L-arginine (L-Arg), is a potent taste stimulus for the channel catfish, Ictalurus punctatus. Receptor binding studies demonstrated a high-affinity binding of L-Arg to putative taste receptor sites. This binding could be inhibited by preincubation of the tissue in the lectins Phaseolus vulgaris agglutinin (PHA) and Ricinus communis agglutinin I (RCA I). Neurophysiological studies demonstrated that the L-Arg receptor is a stimulus-gated ion channel type receptor whose conductance was stimulated by L-Arg and inhibited by D-arginine (D-Arg). To purify the receptor we subjected CHAPS solubilized partial membrane preparation from barbel epithelium to RCA I lectin affinity chromatography. The bound proteins were eluted with D-galactose. When these proteins were reconstituted into lipid bilayers, L-Arg activated single channel currents with conductances between 45 and 85 pS. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the eluted protein showed a distinct band at approximately 83 kDa. Polyclonal antibodies raised against this 83-kDa band in guinea pigs reacted with numerous small (approximately 1 micron) sites within the taste pore of every taste bud when applied to fixed nonpermeabilized barbels. This observation suggests that the antibodies recognize an externally-facing epitope of the putative Arg receptor. The antibodies also inhibited L-Arg-stimulated currents in reconstitution studies. Sephacryl S-300 HR chromatography of the eluant from the affinity column showed a high molecular weight peak (> 700 kDa) which was recognized by the antibodies. Reconstitution of the protein from this peak into a lipid bilayer resulted in L-Arg-stimulated channels that could be inhibited by D-Arg. This high molecular weight component may be aggregates of the arginine taste receptor.

Capsaicin and its analogs induce ion channels in planar lipid bilayers.

The irritating, pungent compound, capsaicin (10-20 microM), induces the formation of non-selective ion channels with a wide variety of conductances in protein-free lipid bilayers form from a mixture of zwitterionic phospholipids. The channel-forming activity of capsaicin and four of its analogs followed the sequence: resiniferatoxin > capsaicin = pelargonic acid vanillylamide > methylcapsaicin >> veratrylamine. The ability to form channels correlated with the biological activity of these compounds observed in other studies that measured 45Ca uptake into rat dorsal root ganglion cells. The correlation obtained suggests that an interaction with the lipid bilayer may be an important component of the biological activity of capsaicin.

Selective modification of sterol composition of hepatomas: new opportunities for chemotherapy.

The absence of feedback regulation of cholesterol biosynthesis in hepatomas suggests the possibility of substitution of cholesterol with its biosynthetic precursors (7-dehydrocholesterol or lanosterol) selectively in hepatomas without the accumulation of these precursors in liver and other normal tissues, by a combination of a high cholesterol diet and specific inhibitors of cholesterol biosynthesis (AY-9944 for accumulation of 7-dehydrocholesterol and ketoconazole for accumulation of lanosterol). We suggest: (1) using a selective accumulation of 7-dehydrocholesterol in hepatoma plasma membranes to increase the sensitivity of hepatoma cells to polyene antibiotics (amphotericin B, nystatin), because polyene antibiotics have higher affinity to 7-dehydrocholesterol compared to cholesterol; (2) using a selective accumulation of lanosterol in hepatoma cells to increase the sensitivity of hepatoma cells to different antitumor agents, because lanosterol is much less effective in supporting vital cell functions (including barrier properties of natural membranes) compared to cholesterol.

[Change of current-voltage characteristics of amphotericin B ion channels accompanying its incorporation into the membrane]. / Izmenenie bol't-ampernoi kharakteristiki ionnykh kanalov amfoteritsina B pri ego vstraivanii v membranu.

Non-linearity of amphotericin B current-voltage characteristics is determined by means of the third harmonic generated in the membrane. A change of the sign of non-linearity is revealed during incorporation of antibiotic molecules into a membrane, i. e. the incorporation is not a simple increase of the number of similar ionic channels in the membrane.

Random dynamical models from time series.

In this work we formulate a consistent Bayesian approach to modeling stochastic (random) dynamical systems by time series and implement it by means of artificial neural networks. The feasibility of this approach for both creating models adequately reproducing the observed stationary regime of system evolution, and predicting changes in qualitative behavior of a weakly nonautonomous stochastic system, is demonstrated on model examples. In particular, a successful prognosis of stochastic system behavior as compared to the observed one is illustrated on model examples, including discrete maps disturbed by non-Gaussian and nonuniform noise and a flow system with Langevin force.

Prognosis of qualitative system behavior by noisy, nonstationary, chaotic time series.

An approach to prognosis of qualitative behavior of an unknown dynamical system (DS) from weakly nonstationary chaotic time series (TS) containing significant measurement noise is proposed. The approach is based on construction of a global time-dependent parametrized model of discrete evolution operator (EO) capable of reproducing nonstationary dynamics of a reconstructed DS. A universal model in the form of artificial neural network (ANN) with certain prior limitations is used for the approximation of the EO in the reconstructed phase space. Probabilistic prognosis of the system behavior is performed using Monte Carlo Markov chain (MCMC) analysis of the posterior Bayesian distribution of the model parameters. The classification of qualitatively different regimes is supposed to be dictated by the application, i.e., it is assumed that some classifier function is predefined that maps a point of a model parameter space to a finite set of different behavior types. The ability of the approach to provide prognosis for times comparable to the observation time interval is demonstrated. Some restrictions as well as possible advances of the proposed approach are discussed.

Using the minimum description length principle for global reconstruction of dynamic systems from noisy time series.

An alternative approach to determining embedding dimension when reconstructing dynamic systems from a noisy time series is proposed. The available techniques of determining embedding dimension (the false nearest-neighbor method, calculation of the correlation integral, and others) are known [H. D. I. Abarbanel, (Springer-Verlag, New York, 1997)] to be inefficient, even at a low noise level. The proposed approach is based on constructing a global model in the form of an artificial neural network. The required amount of neurons and the embedding dimension are chosen so that the description length should be minimal. The considered approach is shown to be appreciably less sensitive to the level and origin of noise, which makes it also a useful tool for determining embedding dimension when constructing stochastic models.

[Role of sterol structure in complex formation with polyene antibiotics]. / Rol' struktury sterina v kompleksoobrazovanii s polienovymi antibiotikami.

The capacity of sterols of different structure being components of artificial bilayer lipid membranes for formation of complexes with polyenic antibiotics, such as amphotericin B, nistatin and levorin was studied. It was shown that sterols delat 5,7-dienic systemin ring B, ergosterol and cholesta-5,7,22-trien 3 beta-ol had the highest affinity to all the 3 antibiotics, while sterols with one double bond in ring B, i. e. cholesterol and brassicasterol had less affinity and sterol without any double bonds in the molecule i.e. 5alpha cholestan 3beta-ol had the least affinity. It was supposed that delta 5,7-sterols had the highest affinity to polyens because of the fact that atoms C-5, C-6; C-7 and C-8 in ring B were practically situated in one plane in contrast to sterols with completely saturated ring B situated in the "conformation chair". Because of this interaction between delta 5,7-sterol ring B and the same flat polyenic site of the antibiotic molecule is sterically most firm since maximum contact is possible between two planes. It was noted that affinity of sterol to the polyenic antibiotics was higher if there were a double bond at 22-23 and methyl group at C-24 in the sterol side chain.

The influence of sterols on the sensitivity of lipid bilayers to melittin.

The sensitivity of planar lipid bilayers to the permeabalizing effect of melittin was evaluated when sterols of varying structure were incorporated into the membrane. The addition of increasing amount of cholesterol (0-50 mole %) decreased the sensitivity of membranes formed from negatively charged phospholipids to melittin but did not (in amount of up to 66 mole %) change the sensitivity of membranes formed from zwitterionic lipids. 7-Dehydrocholesterol, stigmasterol and ergosterol had the same ability as that of cholesterol to decrease the membrane sensitivity to melittin, while lanosterol had no effect on the sensitivity of membranes to melittin. The results suggest that the effect of sterols is complex and cannot be explained only by a direct interaction of melittin with cholesterol, by a decrease of membrane fluidity, or by changes in distribution of surface charge.

[Properties of a Candida albicans strain possessing an increased sensitivity to polyene antibiotics]. / Izuchenie svoistv shtamma Candida albicans, obladaiushchego povyshennoi chuvstvitel'nost'iu k polienovym antibiotikam.

Characteristics of a mutant of the yeast-like fungus Candida albicans with increased sensitivity to amphotericin B, levorin and nystatin is presented. Increased sensitivity to the polyens in the isolate must be associated with changes in the cell wall and/or with decreased total viability of the strain. The following factors were in favour of this: presence of significant amounts of pseudomycelial cells with thinner cell walls as compared to the yeast cells in the population of the mutant strain; a higher rate of potassium liberation from the cells of the mutant strain in the presence of amphotericin B; a lower growth rate of the mutant strain on solid and liquid media; an increased death rate of the cells in the intact culture of the mutant strain as compared to the initial strain; absence of changes in the absorption spectrum of sterols isolated from the cells of the mutant strain as compared to the initial culture.

[Role of sterols in the interaction of polyene antibiotics with lipid membranes]. / Rol' sterinov vo vzaimodeistvii polienovykh antibiotikov s lipidnymi membranami.

The problem whether the membrane sterols are indirect acceptors of polyenic antibiotics or they play the role of substances providing conditions (at the expense of putting in order the membrane phospholipids) for formation of conductive complexes (ionic canals) from the antibiotic molecules is discussed. The comparative study on the ability of sterols of various structure (ergosterol, 7-dehydrocholesterol, cholesterol, 5 alpha-cholestan-3 beta-ol) to interact with the membrane phospholipids and to increase the sensitivity of such membranes to amphotericin B showed no correlation between the levels of these properties. The value of the changes in the cross elasticity module (E) of artificial bilayer lipid membranes from egg lecithin on introduction of the above sterols into their composition was used as the criterion for the interaction level. The absence of correlation between the above properties of the sterols indicated that the role of the sterols in interaction of polyenic antibiotics with the membranes could not be considered as the only effect of the sterols on putting in order the phospholipids, which confirmed the hypothesis on the acceptor function of the sterols with respect to polyenic antibiotics. The study of the effect of amphotericin B on the elastic properties of the cholesterol-containing bilayer membranes isolated from egg lecithin showed tha the values of the longitudinal and cross elasticity modules of the membranes did not change during introduction into the membranes of the ionic canals.

Properties of voltage-gated ion channels formed by syringomycin E in planar lipid bilayers.

Using the planar lipid bilayer technique we demonstrate that the lipodepsipeptide antibiotic, syringomycin E, forms voltage-sensitive ion channels of weak anion selectivity. The formation of channels in bilayers made from dioleoylglycerophosphatidylserine doped with syringomycin E at one side (1-40 micrograms/ml) was greatly affected by cis-positive voltage. A change of voltage from a positive to a negative value resulted in (i) an abrupt increase in the single channel conductance (the rate of increase was voltage dependent) simultaneous with (ii) a closing of these channels and an exponential decrease in macroscopic conductance over time. The strong voltage dependence of multichannel steady state conductance, the single channel conductance, the rate of opening of channels at positive voltages and closing them at negative voltages, as well as the observed abrupt increase of single channel conductance after voltage sign reversal suggest that the change of the transmembrane field induces a significant rearrangement of syringomycin E channels, including a change in the spacing of charged groups that function as voltage sensors. The conductance induced by syringomycin E increased with the sixth power of syringomycin E concentration suggesting that at least six monomers are required for channel formation.