Search

Introduction. Visual impairment is the most common disturbances during the child development in preschool and primary school age. Such children need care with the health-improving technology based on scientific knowledge about the characteristics of their psychophysiological functions. The aim of the study is to identify development-related changes in blood circulation and central nervous system functions in 4-10 year healthy children and cases with visual impairments. Materials and methods. A total of 380 children were examined by electrocardiography, electroencephalography, registration of neurodynamic processes, analysis of the tactile function, and self-assessment of anxiety. Results. In subjects with visual impairment, an increase in age-related heterochronism in the development of psychophysiological functions was revealed. The accuracy indices of time intervals and tactile sensitivity of the skin of the fingers were higher, and the indices of physical development, kinematometry, and mobility of nervous processes in many age groups are lower than in healthy ones. Such adaptive changes were accompanied by an increase in functional stress. So, for example, in preschool children from 4 to 6 years, when analyzing the structure of the heart rhythm, an increase in the values of the stress index was noted (from 148.08 ± 3.32 to 220.08 ± 3.62 c.u.; р < 0.05). Conclusion. Judging by the high values ​​of activity indices of the central mechanisms of heart rhythm regulation, anxiety, and the nature of bioelectric changes on the EEG, the “price” of age-related adaptation in children with sensory impairments rises. It contributes to the development of disadaptation. The conclusion is made about the need to develop effective means of psychophysical correction of children with visual impairments, taking into account the nature of age-related changes.

The determination of the timeframe in which a document was created is applied to verify the authenticity of documents in the investigation of fraud committed by using forged documents. It is known that the document aging process affects the substrate characteristics, the study of which requires physical and chemical research of document details. This article discusses the techniques employed to examine inks, pen pastes, gel, stamp ink and other materials that created the document. Knowledge of methods for determining the age of documents will help investigators, judges and lawyers better select experts and specialists, conduct interrogations, and evaluate their conclusions.

The specificity of the transmission of ideas, methods of perception of various areas of public life, social stereotypes is described. The high potential of the content analysis method in reflecting the key informational factors in the formation of public opinion is shown. The qualitative and quantitative aspects of the content analysis are considered. The importance of studying not only the texts of printed publications, but also publications posted on the Internet, including publications in leading social networks, is described. The significance and prospects for the development of content analysis methods related to the study of large amounts of information are investigated. The perspective of the methods of content analysis based on the involvement of modern information technologies is considered. It is proved that in the course of social development, the importance of the content analysis method increases, which is accompanied by an increase in its capabilities associated with the development of machine technologies for processing large amounts of information.

Boron neutron capture therapy is a unique form of adjuvant cancer therapy for various malignancies including malignant gliomas. The conjugation of boron compounds and human serum albumin (HSA)—a carrier protein with a long plasma half-life—is expected to extend systemic circulation of the boron compounds and increase their accumulation in human glioma cells. We report on the synthesis of fluorophore-labeled homocystamide conjugates of human serum albumin and their use in thiol-‘click’ chemistry to prepare novel multimodal boronated albumin-based theranostic agents, which could be accumulated in tumor cells. The novelty of this work involves the development of the synthesis methodology of albumin conjugates for the imaging-guided boron neutron capture therapy combination. Herein, we suggest using thenoyltrifluoroacetone as a part of an anticancer theranostic construct: approximately 5.4 molecules of thenoyltrifluoroacetone were bound to each albumin. Along with its beneficial properties as a chemotherapeutic agent, thenoyltrifluoroacetone is a promising magnetic resonance imaging agent. The conjugation of bimodal HSA with undecahydro-closo-dodecaborate only slightly reduced human glioma cell line viability in the absence of irradiation (~30 μM of boronated albumin) but allowed for neutron capture and decreased tumor cell survival under epithermal neutron flux. The simultaneous presence of undecahydro-closo-dodecaborate and labeled amino acid residues (fluorophore dye and fluorine atoms) in the obtained HSA conjugate makes it a promising candidate for the combination imaging-guided boron neutron capture therapy.

The main purpose of this study is to identify and justify (from the point of sociological science) the practical use of criteria, indicators and markers that allow to determine the level of public control phenomenon and degree of its effectiveness in a particular state. The obtained results will allow us to determine the features of public control prospective development within a particular area of state policy and identify some specific problems associated with development of the public control institution in relation to the system of public and government social interaction within a particular state entity.

As the most abundant protein with a variety of physiological functions, albumin has been used extensively for the delivery of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare spin-labeled albumin-based multimodal imaging probes and therapeutic agents. We report the synthesis of a tamoxifen homocysteine thiolactone derivative and its use in thiol-‘click’ chemistry to prepare multi-functionalized serum albumin. The released sulfhydryl group of the homocysteine functional handle was labeled with a nitroxide reagent to prepare a spin-labeled albumin–tamoxifen conjugate confirmed by MALDI-TOF-MS, EPR spectroscopy, UV-vis and fluorescent emission spectra. This is the basis for a novel multimodal tamoxifen–albumin theranostic with a significant (dose-dependent) inhibitory effect on the proliferation of malignant cells. The response of human glioblastoma multiforme T98G cells and breast cancer MCF-7 cells to tamoxifen and its albumin conjugates was different in tumor cells with different expression level of ERα in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells.

BODIPY dyes are photostable neutral derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. These are widely used as chemosensors, laser materials, and molecular probes. At the same time, BODIPY dyes have small or moderate Stokes shifts like most other fluorophores. Large Stokes shifts are preferred for fluorophores because of higher sensitivity of such probes and sensors. The new boron containing BODIPY dye was designed and synthesized. We succeeded to perform an annulation of pyrrole ring with coumarin heterocyclic system and achieved a remarkable difference in absorption and emission maximum of obtained fluorophore up to 100 nm. This BODIPY dye was equipped with linker arm and was functionalized with a maleimide residue specifically reactive towards thiol groups of proteins. BODIPY residue equipped with a suitable targeting protein core can be used as a suitable imaging probe and agent for Boron Neutron Capture Therapy (BNCT). As the most abundant protein with a variety of physiological functions, human serum albumin (HSA) has been used extensively for the delivery and improvement of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare albumin-based multimodal constructions. The released sulfhydryl groups of the homocysteine functional handle in thiolactone modified HSA were labeled with BODIPY dye to prepare a labeled albumin-BODIPY dye conjugate confirmed by MALDI-TOF-MS, UV-vis, and fluorescent emission spectra. Cytotoxicity of the resulting conjugate was investigated. This study is the basis for a novel BODIPY dye-albumin theranostic for BNCT. The results provide further impetus to develop derivatives of HSA for delivery of boron to cancer cells.

Background. Gender diferences exist in almost every aspect of our lives. Individuals have an array of diferent social expectations with regard to behaviors, communication,appearance, attitudes, and social roles, but these expectations tend to be based on whether the individual is male or female. Currently, many social studies have been done with the help of virtual reality technologies. Tey have been efectively applied to the study of many social phenomena such as nonverbal communication, social skills training, social anxiety rehabilitation, etc. Recently considerable attention has been paid to issue of gender diferences during social interaction with the virtual partners, avatars. However, the question of gender diferences during interactions with avatars of diverse ethnic appearances has seldom been studied. Objective. Te goal of this study was to investigate the gender peculiarities of interaction with avatars of diferent ethnic appearances. We used the CAVE virtual reality system to study gender diferences in interpersonal distances which were maintained with avatars. Design. We designed four three-dimensional virtual scenes with avatars of four diferent ethnic appearances. Tey were avatars of Slavic, Asian, North Caucasian, and African appearance. All the avatars were male. Te participants (who all identifed as Russians) were immersed in virtual environments with the help of the CAVE virtual reality system. Teir task was to approach the avatar, present herself/himself in any way they wanted, and give instructions for the work. During the task the interpersonal distances between the participants and the avatars were measured. Afer leaving the CAVE, the participants were asked to fll out a questionnaire assessing the Presence efect. Results. Te results showed gender diferences in how much interpersonal distance was maintained: women preferred to keep shorter interpersonal distances with their virtual partners than men did. Moreover, the results showed the impact of ethnic appearance on interpersonal distances. Women approached the avatars of their own ethnic group more closely and kept further away from the avatars of other ethnic groups. Unlike the women, the men stayed the same distance away from the avatars of diferent ethnic groups. Both gender groups kept equally far away from the avatar of African appearance. Gender diferences were also revealed in the participants’ estimates of the Presence efect. Conclusion. We developed a comprehensive method for analyzing the gender differences in interaction with the avatars, including both subjective (the sense of Presence, semantic diferential technique) and objective (assessment of interpersonal distance) characteristics. Tis method allowed us to assess gender variables during the social interaction using both behavioral and psychological responses. Te same method can be applied successfully to the study of gender diferences regarding other social phenomena.

The specificity of the transmission of ideas, methods of perception of various areas of public life, social stereotypes is described. The high potential of the content analysis method in reflecting the key informational factors in the formation of public opinion is shown. The qualitative and quantitative aspects of the content analysis are considered. The importance of studying not only the texts of printed publications, but also publications posted on the Internet, including publications in leading social networks, is described. The significance and prospects for the development of content analysis methods related to the study of large amounts of information are investigated. The perspective of the methods of content analysis based on the involvement of modern information technologies is considered. It is proved that in the course of social development, the importance of the content analysis method increases, which is accompanied by an increase in its capabilities associated with the development of machine technologies for processing large amounts of information.

Human serum albumin is playing an increasing role as a drug carrier in clinical settings. Biotin molecules are often used as suitable tags in targeted anti-tumor drug delivery systems. We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anti-cancer fluorinated nucleotide conjugated with a biotinylated dual-labeled albumin. Interestingly, in vitro and in vivo study revealed stronger anti-tumor activity of the non-tagged theranostic conjugate than that of the biotin-tagged conjugate, which can be explained by decreased binding of the biotin-tagged conjugate to cellular receptors. Our study sheds light on the importance of site-specific albumin modification for the design of albumin-based drugs with desirable pharmaceutical properties.

We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anticancer fluorinated nucleotide conjugated with a dual-labeled albumin. A fluorine-labeled homocysteine thiolactone has been used as functional handle to synthesize the fluorinated albumin and couple it with a chemotherapeutic agent 5-trifluoromethyl-2′-deoxyuridine 5′-monophosphate (pTFT). The conjugate allows for direct optical and 19F magnetic resonance cancer imaging and release of the drug upon addition of glutathione. Interestingly, the pTFT release from albumin conjugate could only be promoted by the increased acidity (pH 5.4). The in vitro study and primary in vivo investigations showed stronger antitumor activity than free pTFT.

Background ― Hypertension is a widespread condition nowadays. Changes in physical activity patterns of the population, namely, sedentary lifestyle and increased loads on small muscle groups, are the key factors behind the development of hypertension. Although science has amassed sufficient amounts of facts about a hypertensive effect of local loads, the very mechanisms underlying adaptive reactions of the circulatory system have not received comprehensive study. Material and Methods ― We studied adaptive reactions to local muscle work in 108 adult subjects groups aged between 18 and 20, 30 and 35, and 60 and 74 respectively by means of a Mosso’s ergograph until the onset of fatigue with all the three age groups receiving medium loads. We have analyzed their work performance, including static and dynamic stamina. We took blood pressure measurements, electrocardiograms (ECGs) and electroencephalograms (EEGs) before and after the test. Results ― We discovered increased heartbeat rates, systolic blood pressure, and diastolic blood pressure in all of the subjects, as they were doing local load tests, while their ECGs showed shortened electric diastole time, which was indicative of heart functional tension, especially in the subjects aged between 18 and, and 60 and 74. Adverse heart reactions were more pronounced while the subjects were doing static tests rather than dynamic tests, and their EEGs showed increased slow-wave activity within alpha- and theta-ranges, with regularly recurrent alpha wave synchronizations. Conclusion ― Our research shows that central mechanisms underlie hypertensive reactions of the cardiovascular system to local loads with the participation of metabolic receptors of muscles. We have also justified the necessity of preventive campaigns against hypertensions in individuals receiving increased amounts of local muscle work in the motor mode.

Photoactivatable derivatives Ar-NH-(CH2)n-NHpppB (where Ar = p-azidophenyl (A1), 5-azido-2-nitrobenzoyl (A2), or 4-azido-2,3,5,6-tetrafluorobenzoyl(A3) group; B = Ado or Guo; n = 2, 3, or 4) were synthesized. The phosphoroamidate bond stability was found to depend on the structure of both the heterocyclic and the photoactivatable groups. The derivative with A3, Ado, and n = 3 is hydrolyzed with regeneration of aryl azide and ATP, whereas the other derivatives are stable in aqueous solutions. The photoanalogues with A1 and A2, B = Ado, and n = 2 or 4 were found to behave as initiating substrates toward the RNA polymerase II from Saccharomyces cerevisiae under the conditions of specific transcription initiation and control of the adenovirus late promoter. The photolysis of N-(4-azidophenyl)-1,4-diaminobutane and N-(5-azido-2-nitrobenzoyl)-1,3-diaminopropane, two functional fragments of the photoaffinity reagents, in aqueous solutions was established to result in the formation of p-benzoquinone diimine and p-nitro-N-arylhydroxylamine derivatives, respectively. The arylhydroxylamine derivatives undergo a number of transformations in aqueous solution leading to nitroso derivatives. We concluded that it is this nitroso derivative (products of nitrene transformation, rather than the nitrenes themselves) that may modify proteins with reagents containing p-nitrophenyl azide fragment.

Irradiation of a complex between N -(5-azido-2-nitrobenzoyl)- N ′-( d -biotinyl)-1,2-diaminoethane ( I ) and streptavidin with light of 313 nm led to the covalent attachment of the photobiotin analogue I to the protein. Streptavidin could also be labelled in the dark with prephotolyzed I . These results indicate that a long-lived reactive intermediate was formed upon irradiation. Moreover, after cleavage of labelled streptavidin with proteinase K this intermediate appears to be covalently attached to the same peptide as the one obtained by direct photoaffinity labelling. An iminosulfurane II derived from the reaction of biotin sulfur atom with aryl nitrene is responsible for the dark-labelling reaction. The photoproduct II converts in an aqueous solution almost completely into N -(5-amino-2-nitrobenzoyl)- N ′-( d -( S -oxo)biotinyl)-1,2-diaminoethane (the half-life of II is 10 days).

Herein, we report a novel strategy to engineer an acid-sensitive anticancer theranostic agent using a vector-drug ensemble. The ensemble was synthesized by directly conjugating the linoleic acid (LA)-modified branched polyethyleneimine with a chemotherapeutic drug trifluorothymidine. Linoleic acid residues were grafted onto 25 kDa polyethyleneimine (PEI) by treating PEI with linoleic acid chloroanhydride. 5-Trifluoromethyl-2'-deoxyuridine (trifluorothymidine, TFT) was introduced into LA-PEI conjugate by phosphorylating the conjugate with amidophosphate of trifluorothymidine 5'-monophosphate (pTFT), which had been activated by its conversion into the N,N-dimethylaminopyridine derivative. The extent of mononucleotide analog incorporation in the polymer was regulated by the ratio of pTFT to the polymer during the synthesis. Samples containing 20-70 TFT residues per PEI molecule were obtained. The cytotoxicity of PEI-LA-pTFT conjugates decreased with increasing nucleotide content, as examined using the MTT method. Due to the presence of fluorine atoms, TFT-based conjugates could be detected directly in the animals by (19)F magnetic resonance imaging. In addition, the presence of the amidophosphate group in PEI-LA-pTFT conjugates allowed their detection by in vivo(31)P NMR spectroscopy. Indeed, the (31)P NMR signal of a phosphoramide (δ ~ 12 ppm) was observed in the mouse muscle tissue treated with PEI-LA-pTFT conjugate along with the signals from endogenous phosphorus-containing compounds. At the same time, the use of PEI-LA-pTFT conjugate for chemotherapeutic drug delivery is limited due to the low release of pTFT from the carrier. To enhance the release of the drug from the conjugate in the endosomes, PEI-LA polymer was coupled with urocanic acid (UA), which bears imidazole ring and thus can form an acid-labile P-N bond with pTFT. The PEI-LA-UA-pTFT conjugate containing 30 residues of UA and 40 residues of pTFT was tested against the murine Krebs-II ascites carcinoma, grown as an ascetic tumor. The intraperitoneal injection of the conjugates resulted in prolongation of the animals' life and to the complete disappearance of the tumor after three injections.

The comparative analysis of RNA-hydrolyzing activity of albumin from human serum and albumin expressed in methylotrophic yeast Pichia pastoris has been carried out. The rate of polyribonucleotide phosphodiester bond cleavage in the presence of recombinant albumin has been found to be similar to that of the reaction mediated by the native protein. According to 31P NMR data, RNA hydrolysis follows the mechanism of intermolecular trans-esterification to yield 2',3'-cyclophosphodiester reaction products that are further slowly hydrolyzed to form nucleoside-3'- and nucleoside-2'-phosphates. Analysis of pH dependence suggests an acid-base mechanism of catalysis. The catalytic activity and substrate specificity of albumin in RNA hydrolysis distinguish it from human ribonucleases.

Photoanlogues of the initiation substrates of the RNA polymerase II, N3ArNH(CH2)(n)NHpppA where N3Ar is 5-azido-2-nitrobenzoyl group (n = 2 or 4) were synthesized, allowing the preparation of photoreactive oligonucleotides in situ by RNA polymerase II for application as photolabels. Photolysis of p-nitro-substituted aromatic azide in aqueous medium was investigated. Using the azoxy-coupling reaction it was possible to determine whether a nitrene or p-nitrophenyl hydroxylamine azoxy compound is the trappable intermediate that is generated at ambient temperature in aqueous solution.