Философско-методологические аспекты современных интеллектуальных технологий

У статті здійснюється аналіз сучасних інтелектуальних технологій, виявляються їх тенденції розвитку в напрямку домінанти інформаційно-образних систем. Здійснюється обґрунтування необхідності формування нової методології образних структур. Досліджувані проблеми відображають процеси духовних трансформацій, що пов’язані з парадигмальними змінами в системі сучасної науки і культури.The analysis of modern intellectual technologies is carried out; their tendencies of development in a direction of a dominant of information-pattern systems are opened in article. The necessity of new methodology formation of pattern structures is proved. The researched problems represent processes of cultural transformations, which are connected with paradigmatic changes in system of a modern science and culture.В статье осуществляется анализ современных интеллектуальных технологий, раскрываютя их тенденции развития в направлении доминанты информационно-образных систем. Обосновывается необходимость формирования новой методологии образных структур. Исследуемые проблемы отображают процессы духовных трансформаций, которые связаны с парадигмальными изменениями в системе современной науки и культуры

Simulation of interaction of production systems of industrial enterprises and business groups

The article considers the system of industrial enterprises constituting a business group, jointly producing some final product, supplying it with their private products. Since, in general, the capacities of enterprises are different, their products are not produced in proportional volumes, which simultaneously leads to both overstocking and the formation of a shortage of individual components of the final product. This leads to a decrease in the overall efficiency of the business group and to the instability of its individual enterprises. In the study, the task has been set to develop a mathematical model and a mechanism for a coordinated and fairly evaluated activity of enterprises using the basic concepts of the theory of active systems. The proposed model design is based on the requirements: private products must be supplied by enterprises in the required proportions, and penalties for failure to complete tasks must be characterized by a single penalty coefficient. In particular, in the development of well-known approaches to reconcile the conflicting interests of two different economic entities, it is proposed:– to clarify the area of agreed decisions by expanding it, taking into account not only the possibility of exceeding the optimal task for the enterprise, but also its underestimation;– to form a criterion for assigning penalty coefficients, as the equality of the lower value of the region of feasible solutions of a stronger enterprise and the upper value of the region of feasible solutions of a weaker enterprise.The solution of the problem is generalized to the case of an arbitrary number of enterprises. A general algorithm for solving the problem has been developed, including determining two critical enterprises, calculating the allowable (agreed) volume of product output for them, calculating the corresponding penalty coefficient and the values of output of individual products for each enterprise. An illustrative example has been given

A Gating Hinge in Na+ Channels A Molecular Switch for Electrical Signaling

AbstractVoltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the α helix, greatly enhances activation by shifting its voltage dependence −51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our results fit a model in which concerted bending at glycine 219 in the S6 segments of NaChBac serves as a gating hinge. This gating motion may be conserved in most members of this large ion channel protein family

Uveal melanoma dissemination within the scleral tract in fine needle aspiration biopsy

Introduction. Fine needle aspiration biopsy (FNAB) of uveal melanoma (UM) is an invasive procedure. Many authors consider UM FNAB to be safe procedure, however extraocular extension of the tumor through the scleral tracts may occur. Current studies of scleral tracts after FNAB do not compare different biopsy techniques (cannula-assisted and without cannula) in terms of UM cells.Purpose. To assess morphology of scleral tracts for the presence of malignant cells when different biopsy techniques are approached.Material and methods. Forty-four scleral samples were analyzed after transvitreal FNAB performed in 22 enucleated eyes with UM. Cannula-assisted FNAB was performed in 22 cases. In the same eyes FNAB (n=22) was performed without cannula.Results. FNAB material was adequate for cytological examination in all cases. UM was confirmed in 22 eyes pathologically. UM cell implantation was detected in 5 scleral samples after FNAB without cannula. No signs of cell implantation were seen after cannula-assisted FNAB. The risk of scleral tract UM cell implantation was statistically lower in cannula-assisted FNAB technique (p=0.018, Pearson Chi-square test).Conclusions. UM FNAB performed directly through the sclera without cannula is associated with tumor cells implantation in scleral tract. Cannula-assisted FNAB significantly reduces the incidence of UM implantation in scleral tract

Cooperativity of Kv7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells.

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency. Here, we report ultrafast electromechanical gating of clustered Kv7.4 in OHCs. Increases in kinetics and sensitivity resulting from cooperativity among clustered-Kv7.4 were revealed, using optogenetics strategies. Upon clustering, the half-activation voltage shifted negative, and the speed of activation increased relative to solitary channels. Clustering also rendered Kv7.4 channels mechanically sensitive, confirmed in consolidated Kv7.4 channels at the base of OHCs. Kv7.4 clusters provide OHCs with ultrafast electromechanical channel gating, varying in magnitude and speed along the cochlea axis. Ultrafast Kv7.4 gating provides OHCs with a feedback mechanism that enables the cochlea to overcome viscous drag and resolve sounds at auditory frequencies

The modern view on the surgical treatment of nephrolithiasis

The choice of surgical treatment for nephrolithiasis remains a matter of debate. The article is a literature review dedicated to a comparative analysis of the efficacy and safety of extracorporeal shock-wave lithotripsy (ESWL) and endoscopic methods for the treatment of nephrolithiasis. The literature review was based on the analysis of articles published in the PubMed / MEDLINE, and eLibrary databases. Sixty publications on the topic of the review were analysed. As a result of data analysis, endoscopic therapies have a significant advantage over ESWL with comparable safety. The development and dissemination of less invasive techniques such as mini-percutaneous nephrolithotripsy and ultra-mini-percutaneous nephrolithotripsy in the future may change the approach to the surgical treatment of any form of nephrolithiasis

First insights into structure-function relationships of alkylglycerol monooxygenase

Alkylglycerol monooxygenase is a tetrahydrobiopterin-dependent enzyme that cleaves the O-alkyl-bond of alkylglycerols. It is an exceptionally unstable, hydrophobic membrane protein which has never been purified in active form. Recently, we were able to identify the sequence of alkylglycerol monooxygenase. TMEM195, the gene coding for alkylglycerol monooxygenase, belongs to the fatty acid hydroxylases, a family of integral membrane enzymes which have an 8-histidine motif crucial for catalysis. Mutation of each of these residues resulted in a complete loss of activity. We now extended the mutational analysis to another 25 residues and identified three further residues conserved throughout all members of the fatty acid hydroxylases which are essential for alkylglycerol monooxygenase activity. Furthermore, mutation of a specific glutamate resulted in an 18-fold decreased affinity of the protein to tetrahydrobiopterin, strongly indicating a potential important role in cofactor interaction. A glutamate residue in a comparable amino acid surrounding had already been shown to be responsible for tetrahydrobiopterin binding in the aromatic amino acid hydroxylases. Ab initio modelling of the enzyme yielded a structural model for the central part of alkylglycerol monooxygenase where all essential residues identified by mutational analysis are in close spatial vicinity, thereby defining the potential catalytic site of this enzym

Catalytic residues and a predicted structure of tetrahydrobiopterin-dependent alkylglycerol mono-oxygenase

Alkylglycerol mono-oxygenase (EC 1.14.16.5) forms a third, distinct, class among tetrahydrobiopterin-dependent enzymes in addition to aromatic amino acid hydroxylases and nitric oxide synthases. Its protein sequence contains the fatty acid hydroxylase motif, a signature indicative of a di-iron centre, which contains eight conserved histidine residues. Membrane enzymes containing this motif, including alkylglycerol mono-oxygenase, are especially labile and so far have not been purified to homogeneity in active form. To obtain a first insight into structure–function relationships of this enzyme, we performed site-directed mutagenesis of 26 selected amino acid residues and expressed wild-type and mutant proteins containing a C-terminal Myc tag together with fatty aldehyde dehydrogenase in Chinese-hamster ovary cells. Among all of the acidic residues within the eight-histidine motif, only mutation of Glu137 to alanine led to an 18-fold increase in the Michaelis–Menten constant for tetrahydrobiopterin, suggesting a role in tetrahydrobiopterin interaction. A ninth additional histidine residue essential for activity was also identified. Nine membrane domains were predicted by four programs: ESKW, TMHMM, MEMSAT and Phobius. Prediction of a part of the structure using the Rosetta membrane ab initio method led to a plausible suggestion for a structure of the catalytic site of alkylglycerol mono-oxygenase