Contradictions in the development of architecture science

The aim of the research is to study the formation of the ontological foundations of the science of architecture as an experience of its self-consciousness in the context of the evolution of spatial codes of cultural experience. The article considers contradictions of the modernist definition of architectural form, as well as the formation of the scientific discourse of architecture and the identity of architects’ professional thinking in general. The main hypothesis is based on the thesis that the freely historically unfolding evolution of architectural form is an objective experience of consolidating the self-consciousness of architecture as a text of its immanent expression and self-reference. The authors specify the limitations of the scientific functionalist discourse, which do not allow forming the internal basis for an autoreferential image of the architectural reality. Problematization of the ontological foundations of the science of architecture is a necessary link in the evolution of the methodology of architectural thinking and form making in post-industrial society

Silica clay (opoka) as a promising raw material for unfired wall products by compression molding

The article is devoted to the actual problem of producing unburnt wall products of compression molding with improved and high efficiency in terms of thermal and engineering properties. The article notes the relevance, attractiveness, and wide use of unburnt pressed products in modern civil engineering. The raw material composition and production technology of unburnt wall products of compression molding are described. The traditionally used aggregates for unburnt wall products of compression molding are reviewed and their properties are analyzed. High average density and high thermal conductivity are noted in these products. The objective is to improve the thermal characteristics of these products while ensuring their strength properties. For this purpose, it is proposed to introduce a porous component of siliceous rock called opoka (silica clay) into the raw material composition of products as a mineral filler. Opoka collected from three different deposits was reviewed, its characteristics given, and the raw material analyzed. It is noted that the porosity and average density of opoka depend on its deposit. The effect of porosity and average density of opoka on the average density, compressive strength, and water absorption of unburnt wall products of compression molding based on opoka with different porosities from different deposits is described. The effect of the properties of opoka on the properties of unburnt wall products of compression molding is explained. It is confirmed that the use of opoka in the production of unburnt wall products reduces the average density of the products and improves their thermal and engineering properties. The appropriateness of manufacturing large-sized hollow wall blocks based on opoka is substantiated

Escherichia coli inorganic pyrophosphatase : site-directed mutagenesis of the metal binding sites

AbstractAspartic acids 65, 67, 70, 97 and 102 in the inorganic pyrophosphatase of Escherichia coli, identified as evolutionarily conserved residues of the active site, have been replaced by asparagine. Each mutation was found to decrease the κapp value by approx. 2–3 orders of magnitude. At the same time, the Km values changed only slightly. Only minor changes take place in the pK values of the residues essential for both substrate binding and catalysis. All mutant variants have practically the same affinity to Mg2+ as the wild-type pyrophosphatase

Mg2+ activation of Escherichia coli inorganic pyrophosphatase

AbstractFurther refinement of X-ray data on Escherichia coli inorganic pyrophosphatase [Oganessyan et al. (1994) FEBS Lett. 348, 301–304] to 2.2 Å reveals a system of noncovalent interactions involving Tyr55 and Tyr141 in the active site. The pKa for one of the eight Tyr residues in wild-type pyrophosphatase is as low as 9.1 and further decreases to 8.1 upon Mg2+ binding, generating characteristic changes in the absorption spectrum. These effects are lost in a Y55F but not in a Y141F variant. It is suggested that the lower-affinity site for Mg2+ in the enzyme is formed by Tyr55 and Asp70, which are in close proximity in the apo-enzyme structure

Residue Network Involved in the Allosteric Regulation of Cystathionine β-Synthase Domain-Containing Pyrophosphatase by Adenine Nucleotides

Inorganic pyrophosphatase containing regulatory cystathionine β-synthase (CBS) domains (CBS-PPase) is inhibited by adenosine monophosphate (AMP) and adenosine diphosphate and activated by adenosine triphosphate (ATP) and diadenosine polyphosphates; mononucleotide binding to CBS domains and substrate binding to catalytic domains are characterized by positive cooperativity. This behavior implies three pathways for regulatory signal transduction — between regulatory and active sites, between two active sites, and between two regulatory sites. Bioinformatics analysis pinpointed six charged or polar amino acid residues of Desulfitobacterium hafniense CBS-PPase as potentially important for enzyme regulation. Twelve mutant enzyme forms were produced, and their kinetics of pyrophosphate hydrolysis was measured in wide concentration ranges of the substrate and various adenine nucleotides. The parameters derived from this analysis included catalytic activity, Michaelis constants for two active sites, AMP-, ATP-, and diadenosine tetraphosphate-binding constants for two regulatory sites, and the degree of activation/inhibition for each nucleotide. Replacements of arginine 295 and asparagine 312 by alanine converted ATP from an activator to an inhibitor and markedly affected practically all the above parameters, indicating involvement of these residues in all the three regulatory signaling pathways. Replacements of asparagine 312 and arginine 334 abolished or reversed kinetic cooperativity in the absence of nucleotides but conferred it in the presence of diadenosine tetraphosphate, without effects on nucleotide-binding parameters. Modeling and molecular dynamics simulations revealed destabilization of the subunit interface as a result of asparagine 312 and arginine 334 replacements by alanine, explaining abolishment of kinetic cooperativity. These findings identify residues 295, 312, and 334 as crucial for CBS-PPase regulation via CBS domains.</p

Regulatory Roles of Cellular Diacylglycerol

Kinetics of diacylglycerol and C1 domain interaction Lipids in biological membranes play significant roles in cellular signaling. Lipids vary not only in head groups but also in acyl chains. It has been reported that the acyl chain of lipids plays an important role in membrane curvature and signal transduction. In this work we investigated the importance of the degree of unsaturation in the acyl chain of diacylglycerol (DAG) in its interaction with the C1 domain. Fluorescence quenching assay showed that DAG with a highly unsaturated acyl chain binds more tightly to the C1 domain than DAG with saturated acyl chains. Moreover, our single molecule tracking studies using supported lipid bilayers as a model system and NIH 3T3 cells explain the kinetic aspect of that binding. Although more unsaturated DAG binds C1 domain tighter it dissociates from the membrane faster than in case of saturated DAG. This finding can explain why unsaturated lipids participate in cell signaling when saturated lipids mainly play a role of bulk lipids. This work provides the new inside about the dynamics of protein-lipid interaction. Extracellular function of diacylglycerol The heterogeneous distribution of lipid molecules in biological membranes depends on a specific region and situation. Selective distribution between bilayer leaflets can be achieved through diffusion (flip-flop) across membranes. DAG is one these lipids which is able to flip-flop rapidly because of a small, uncharged head group. Since the precise cellular localization of DAG determines its function and activity, it is important to understand its distribution and dynamics within a membrane leaflet and between inner and outer parts of cellular bilayers. We developed DAG sensor using mutagenesis and chemical labeling, which allowed accurate quantification of the lipid. Using this sensor we were able to detect very low concentration of DAG at the plasma membrane. It was found that ATP activation in NIH 3T3 cells elevates DAG in plasma membrane 5-7 times. Preliminary data suggest a significant basal level of DAG. It is known that there are two major sources of DAG: from phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylcholine (PC) and both can be initiated by ATP. Physiological roles of exofacial DAG remain unknown. It requires further investigation to understand the flip-flop process and its initiation. We discuss the novel four-color imaging with application of ratiometric analysis that can resolve these questions

Silica clay (opoka) as a promising raw material for unfired wall products by compression molding

The article is devoted to the actual problem of producing unburnt wall products of compression molding with improved and high efficiency in terms of thermal and engineering properties. The article notes the relevance, attractiveness, and wide use of unburnt pressed products in modern civil engineering. The raw material composition and production technology of unburnt wall products of compression molding are described. The traditionally used aggregates for unburnt wall products of compression molding are reviewed and their properties are analyzed. High average density and high thermal conductivity are noted in these products. The objective is to improve the thermal characteristics of these products while ensuring their strength properties. For this purpose, it is proposed to introduce a porous component of siliceous rock called opoka (silica clay) into the raw material composition of products as a mineral filler. Opoka collected from three different deposits was reviewed, its characteristics given, and the raw material analyzed. It is noted that the porosity and average density of opoka depend on its deposit. The effect of porosity and average density of opoka on the average density, compressive strength, and water absorption of unburnt wall products of compression molding based on opoka with different porosities from different deposits is described. The effect of the properties of opoka on the properties of unburnt wall products of compression molding is explained. It is confirmed that the use of opoka in the production of unburnt wall products reduces the average density of the products and improves their thermal and engineering properties. The appropriateness of manufacturing large-sized hollow wall blocks based on opoka is substantiated

The Impact of an Enterprise’s Intellectualization on Its Leadership Potential

The intellectualization of medical companies is gaining special importance in modern conditions of sustainable development, including the minimization of coronavirus consequences. The study aims to form a methodological approach to assess the impact of enterprise intellectualization on the level of leadership potential in the context of stimulating its components. The study demonstrates the effectiveness of a system of factors for achieving leadership based on the intellectualization of Russian clinics, as well as the construction of a synergistic mechanism for combining factors with each other. The scientific contribution of the study is the proposed methodological toolkit for a comprehensive assessment of the impact of a company’s intellectualization on its leadership potential. It provides an opportunity to prioritize the management potential of skills, abilities, and capabilities in order to create a competitive advantage of an enterprise, achieve strategic goals, and form leadership positions in the market. Most of the studied companies were characterized by a lack of balance between leadership potential components in the context of intellectualization. Determining the level of leadership potential development based on companies’ intellectualization demonstrated that the level of qualifications determines the corresponding capabilities, which stimulate the development of a clinics’ personnel. The tested model of assessing the leadership potential of the studied companies’ personnel proves that intellectualization of general clinics influences their leadership potential. It also contributes to sustainable development in the context of actualizing their social component (namely, increased efficiency of medical services, their quality, and, accordingly, the level of health care in general)

"Start-Up" in E-Learning Mode as a Basic Project of the Final Year of Entrepreneurship Education

The study discusses the main positive aspects of the implementation of start-up projects at universities. In the context of the migration of most of the businesses to the network, the most important skill of an entrepreneur is the ability to build an online business from the very first steps. The basis for this is the creation a start-up in e-learning mode. A sample of domestic and foreign universities has been designed to compare new domestic practices with foreign experience of e-learning in entrepreneurship. It has been confirmed that the introduction of start-ups in e-learning mode in the final year of entrepreneurship education positively affects the development of professional qualities of students both in online and off-line business and helps to better consolidate the material. In addition, based on the work done, a final year model of entrepreneurship education with e-learning has been proposed; it is based on 3 main components (the student as a generator of ideas; the mentor as necessary support, and information online channels as the main source of information) and is aimed at solidifying knowledge through the start-up project defense. The importance of the role of universities in this process has been proved and the idea of involving a business mentor in e-learning process to achieve a synergistic effect has been considered