[A study of protein structure changes during hydration by means of diffuse X-ray scattering. II. Fourier transform analysis of X-ray scattering data].

Radial distribution functions were deduced by Fourier transform analysis of angular dependences of diffuse x-ray scattering intensities for the following proteins with different hydration degree: water-soluble a-protein myoglobin, water-soluble alpha+beta protein lysozyme, and transmembrane proteins of photosynthetic reaction centers from purple bacteria Rhodobacter sphaeroides and Blastochlorii viridis. The results of Fourier analysis of x-ray scattering intensities give the quantitative characteristics of the mechanisms underlying the influence of water on the formation of biomacromolecules. Water, on the one hand, weakens the intraglobular hydrogen bond net, loosens the protein structure, and increases the internal conformational dynamics. Concurrently water arranges the stability and ordering of the macromolecule. A sharp correlation is observed between the shift of the "first" peak of radial distribution functions, the weakening of the intraglobular hydrogen bond net, the increase in intraglobular mobility, and the appearance of functional activity in macromolecules. The behavior of the "first" peak is similar to that observed in transmembrane protein of reaction center and water-soluble proteins. The "first" peak for transmembrane protein of reaction center reaches its maximum value much faster (at smaller hydration degrees) than for water-soluble proteins. The fast transfer of reaction center protein to its native state during hydration is due to the fact that the dehydrated conformation of reaction center protein is very close to the native one. From a comparison of the radial distribution functions for water, water-soluble proteins and transmembrane proteins, one may conclude that water has the lowest packing density and the lowest order; water-soluble proteins have a larger packing density and are more ordered than water, and transmembrane proteins have the highest degree of packing density and ordering.

[Experience of application of intellectual computer technologies in the treatment-and-diagnostic practice].

To improve the screening system, the early pre-clinical diagnosis, the choice of therapeutic tactics and medicaments for treating some diseases about 1800 patients were investigated with the use of up-to-date technologies. The new method allows the physicians optimizing the process of decision making and improving the significant element of demonstration medicine, i.e. the transformation of investigational results into argumentative practical recommendations. The method's precision reached 93%.

[A study of protein structure changes during hydration by diffuse X-ray scattering. I. The intensity and the shape of "10-angstrom" maximum].

The angle dependencies of diffuse x-ray scattering intensities were studied in a wide range of angles from 3 to 80 degrees for water-soluble and membrane proteins with a different structural organization: alpha-helical protein myoglobin, alpha-helical protein serum albumen, alpha + beta protein lysozyme, and transmembrane proteins of photosynthetic reaction centers (RC) from purple bacteria Rhodobacter sphaeroides, and Blastochlorii (Rhodopseudomonas) viridis containing cytocrome c, situated out side the membrane, and for H and L+M subunits of membrane protein of reaction center from Rb. sphaeroides for various hydration degrees. The hydration/dehydration process was studied for water-soluble proteins (within hydration range from h = 0.05 to h = 1). The hydration/dehydration process appears to be reversible. All water-soluble proteins show a 10 angstroms peak, and proteins of reaction center do not show this peak. A quantitative comparable study of the behaviour for of the 10 angstroms peak different proteins the degree of lysozyme hydration increases from h = 0.05 to h = 0.45, the protein structure slightly changes (most probably the motifoffolding), the structure of myoglobin in solution is slightly different from the structure in crystal. By taking into account the changes in the shape and intensity of the 10 angstroms peak only, it is impossible to make the conclusion about structural changes in other proteins studied. A correlation between the structural changes observed and dynamic and functional properties of proteins is discussed.

[Equilibrium fluctuations in myoglobin and lysozyme]. / Ravnovesnye fluktuatsii v mioglobine i lizotsime.

The angular dependencies of inelastic intensities of Rayleigh scattering of Moessbauer radiation were measured for myoglobin and lysozyme (in the hydration range h = 0.05-0.7). The data were fitted within the framework of model, when two types of intraglobular motions were taken into account: individual motions of small side-chain groups and cooperative motions of segments. The best agreement with the experiment at h > 0.05 was obtained when individual motions of small groups together with the cooperative motions of alpha-helices and beta-sheets for lysozyme, and alpha-helices for myoglobin were considered. At further hydration (h = 0.45), mean-square displacements (x2) of both types of motions strongly increase with the increase in hydration degree, while the motions with a large correlation radius (not less than macromolecule radius) remain nearly the same as for h = 0.05. The results of the study of the radial distribution function deduced by Fourier-transform from the diffuse x-ray measurements together with RSMR data allow one to conclude that the water during protein hydration competes with the intramolecular hydrogen bonds, loosens the protein and increases the internal dynamics. Concurrently, water arranges the ordering of macromolecule, which takes the native structure at h = 0.4-0.7. The analysis of auto and cross-correlation functions of bending fluctuations of alpha-helices in the large domain of lysozyme performed by molecular dynamics allows one to come to the final conclusion that it is the difference in the structural organization of myoglobin and lysozyme and not the presence of SS-bonds in lysozyme macromolecule that is responsible for different structural fluctuations in these proteins.

[Neural network model of treatment policy decision in patients with ulcer disease]. / Neirosetevaia model' opredeleniia lechebnoi taktiki u bol'nykh iazvennoi bolezn'iu.

Based on neuronetwork computer technologies expert neuronetwork complex Axon was developed providing individual prognosis of ulcer disease and recommendations. The base of this expert system is information data base consisting of two blocks. The first block consists of detailed information about 634 patients with gastric ulcers (GU), the second block - about 417 patients with duodenal ulcers (DU). Control evaluation of the system demonstrated that the coefficient of sensitivity in patients with GU was 0,706 - 0,724, coefficient of specificity - 0,701-0,790. Coefficient of sensitivity in patients with DU was 0,765-0,817, coefficient of specificity - 1,000-0,877. The best neuronetwork evaluation was carried out in 57 new hospitalized patients. In 7 of 10 operated patients indications for surgery were based on combination of prognostic and clinical data. Only 2 (4,3%) of 47 patients demonstrated disagreement of prognostic and clinical data. In comparison of results of complications prognosis with real clinical results in surgical group 7 (70,0%) of 10 patients demonstrated agreement of these data. In 32 (74,4%) of 43 patients treated conservatively prognosis of complications corresponded to real clinical data.

Spatio - temporal features of protein specific motions. The influence of hydration.

The angular dependencies of inelastic intensities of Rayleigh scatteringof Moessbauer radiation were measured for lysozyme and myoglobin (fordifferent degrees of hydration: from h = 0.05 till h = 0.7). The treating ofthe data at h > 0.05 approves the existence of segmental motions(α-helices for myoglobin, α-helices and ß-sheets forlysozyme) as well as of individual motions. Further hydration increase themean-square displacements for both types of intraglobular motions for theseproteins, while the motions of the globule as a whole remain nearlythe same as for h = 0.05. Results of the study of the radial distributionfunction deduced by Fourier - transform from the diffuse x-raymeasurements together with RSMR data allow to conclude that the waterduring hydration of proteins competes with the intramolecular hydrogenbonds, loosens the protein and increases the internal dynamics. At the sametime water arranges the ordering of macromolecule from `glassy' state ath ≈ 0.02 to the native state at h = 0.4-0.7. Differentarchitecture of proteins leads to the different structural dynamics as in thecase of lysozyme and myoglobin.

[The use of artificial neuronal networks in the treatment of peptic ulcer]. / Primenenie iskusstvennykh neironnykh setei v lechenii iazvennoi bolezni.

Today the use of artificial neuronic nets (ANN) is the most perspective method in the prediction of clinical course and in the choice of correct therapeutic tactics. The experimental complex "Axon" with the software was created in the hospital that permitted to predict the course if gastric and duodenal ulcers. We introduced the data of 909 patients that contained the anamnesis, results of objective examination and late results of the treatment. These data has become the base for training and formation of ANN similar to the structure of human cerebral cortex. Having received the information about a new patient and using the previous experience of therapy of 909 patients mentioned above the trained ANN gives an accurate information concerning this patient. It is presented in the form of protocol of prognosis of ulcer clinical course, the probability of complication development, the results of conservative and surgical treatment. The protocol includes the conclusion with recommendations on the choice of therapeutic tactics.

[Use of neural network computer technology in the determination of therapeutic strategy in patients with stomach and duodenal ulcer]. / Primenenie neirosetevykh komp'iuternykh tekhnologii v opredelenii lechebnoi taktiki u bol'nykh s iazvennoi bolezn'iu zheludka i dvenadtsatisperstnoi kishki.

The authors present the expert neural network programmed complex "Axon" allowing the prognosis of the course of ulcer disease of the stomach and duodenum to be made. On the basis of the prognosis obtained certain medical strategy can be recommended. The neural network in which the data of treatment of 909 patients with ulcer disease of the stomach and duodenum had been introduced was taken as a basis of the complex. The program is registered in the Russian copyright agency for PC programs, data base and topologies of integrated circuits. The authors consider that the approach proposed will allow the correct medical policy to be chosen which can lead to better results of treatment of patients with ulcer disease and thus the 100 years long contradictions between different specialists in determining medical policy for such category of patients will be overcome.