Institutional analysis of resource potential for knowledge generation in the enterprises of the regional military-industrial sector

This article discusses the processes of knowledge generation in the enterprises of the military-industrial sector that are the leaders of innovation in the region. The purpose of the study is to develop a methodology based on using the resource potential to improve the efficiency of knowledge generation in the instrument- making enterprises of the military-industrial sector. The authors conducted a system analysis of knowledge generation in one of the enterprises of the military-industrial sector that led to the conclusion on the chaotic character of knowledge generation in such enterprises and its insufficient provision with institutions. The authors proposed a method for designing a knowledge generation system in the enterprises of the regional military-industrial sector by taking into account the means and capabilities of the enterprise in the implementation of intellectual activities. The developed method is based on defining the horizontal resource potential of knowledge generation and allows to determine the potential use of resources at each stage of the product lifecycle. The comparison of actual and theoretical values of horizontal resource potential will allow to adjust the allocation of share held by each of the resources within the stage, and thereby optimize the implementation of tasks at a particular stage. The proposed tools were tested in 2015 in one of the enterprises of the regional military-industrial sector. The methodological tools used in this study include such methods as the expert assessment, mathematical statistics and institutional analysis. The proposed methodology and empirical results have been used as a basis to develop the institutional spiral of knowledge generation during the performance of state order in the enterprises of the military-industrial sector, the implementation of which will help to reduce the level of uncertainty throughout the entire lifecycle of innovative product. The developed institutional spiral of knowledge generation in the instrument-making enterprises of the military-industrial sector involves the provision of incentives for knowledge generation at each stage of the product lifecycle. The results of this study can be used to build the diagram of knowledge generation and apply the procedures for increasing the efficiency of knowledge generation in the enterprises of the military-industrial sector

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkyne

Detection of IgG against Rickettsia typhi: a population-based study in southern Kazakhstan

Uvod. Rickettsia typhi svrstava se u skupinu pjegavih tifusa i uzrokuje endemski tifus. Slučajevi endemskog tifusa i seropozitivnosti na R. typhi zabilježeni su u susjednoj Kini i Rusiji. Međutim, o endemskom tifusu u Kazahstanu se malo zna. Svrha ove studije bila je procijeniti prevalenciju IgG protutijela na R. typhi u populaciji južne regije Kazahstana. Metode. U istraživanje je uključeno ukupno 253 osoba (142 žena, 111 muškaraca) u dobi od 1 do 71 godine. Detekcija serumskih IgG protutijela na R. typhi provedena je imunoenzimskim ELISA testom. Rezultati. Ukupna seropozitivnost na R. typhi iznosila je 34,4%. Najveća seroprevalencija od 91,8% zabilježena je u regiji Turkestan. Najniža seropozitivnost od 6,1% otkrivena je u selu Lepsinsk, regija Almaty. Seroprevalencija se nije značajno razlikovala prema spolu. Seropozitivnost kod odraslih pojedinaca nije bila značajno povezana s dobi, ali pozitivni rezultati nisu otkriveni u dobnoj skupini djece mlađe od 14 godina. Zaključak. Dobiveni rezultati potvrđuju aktivnu cirkulaciju R. typhij u regijama Turkestan i Almaty u Kazahstanu. Podaci ukazuju na hitnu potrebu za daljnjim istraživanjima čiji je cilj procijeniti klinički učinak R. typhi u južnoj regiji Kazahstana.Background. Rickettsia typhi belongs to the typhus group of rickettsiae and causes endemic typhus. Cases of endemic typhus and seropositivity to R. typhi have been reported in the neighbouring China and Russia. However, little is known of the endemic typhus in Kazakhstan. The purpose of this study was to evaluate the prevalence of IgG antibodies to R. typhi in the population of southern region of Kazakhstan. Methods. A total of 253 individuals (142 women, 111 men) aged from 1 to 71 years were recruited into the study. Detection of serum IgG antibodies against R. typhi was performed by enzyme-linked immunosorbent assay (ELISA). Results. The overall R. typhi seropositivity has reached 34.4%. The highest seroprevalence of 91.8% was recorded in the Turkestan Region. The lowest seropositivity of 6.1% was detected in the village Lepsinsk, Almaty Region. The seroprevalence did not differ significantly between genders. Seropositivity in adult individuals was not significantly associated with age, but positive results were not detected in the age group of children under 14 years. Conclusion. The obtained results confirm active circulation of R. typhi in the Turkestan and Almaty Regions of Kazakhstan. The data indicate an urgent need for further studies aimed to evaluate the clinical impact caused by R. typhi in the southern region of Kazakhstan

Mineralogical and geochemical analysis of Fe-phases in drill-cores from the Triassic Stuttgart Formation at Ketzin CO₂ storage site before CO₂ arrival

Reactive iron (Fe) oxides and sheet silicate-bound Fe in reservoir rocks may affect the subsurface storage of CO2 through several processes by changing the capacity to buffer the acidification by CO2 and the permeability of the reservoir rock: (1) the reduction of three-valent Fe in anoxic environments can lead to an increase in pH, (2) under sulphidic conditions, Fe may drive sulphur cycling and lead to the formation of pyrite, and (3) the leaching of Fe from sheet silicates may affect silicate diagenesis. In order to evaluate the importance of Fe-reduction on the CO2 reservoir, we analysed the Fe geochemistry in drill-cores from the Triassic Stuttgart Formation (Schilfsandstein) recovered from the monitoring well at the CO2 test injection site near Ketzin, Germany. The reservoir rock is a porous, poorly to moderately cohesive fluvial sandstone containing up to 2–4 wt% reactive Fe. Based on a sequential extraction, most Fe falls into the dithionite-extractable Fe-fraction and Fe bound to sheet silicates, whereby some Fe in the dithionite-extractable Fe-fraction may have been leached from illite and smectite. Illite and smectite were detected in core samples by X-ray diffraction and confirmed as the main Fe-containing mineral phases by X-ray absorption spectroscopy. Chlorite is also present, but likely does not contribute much to the high amount of Fe in the silicate-bound fraction. The organic carbon content of the reservoir rock is extremely low (<0.3 wt%), thus likely limiting microbial Fe-reduction or sulphate reduction despite relatively high concentrations of reactive Fe-mineral phases in the reservoir rock and sulphate in the reservoir fluid. Both processes could, however, be fuelled by organic matter that is mobilized by the flow of supercritical CO2 or introduced with the drilling fluid. Over long time periods, a potential way of liberating additional reactive Fe could occur through weathering of silicates due to acidification by CO2

4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic Acid. Peculiarities of Preparation, Structure, and Biological Properties

In order to determine the regularities of the structure–analgesic activity relationship, the peculiarities of obtaining, the spatial structure, and biological properties of 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid and some of its derivatives have been studied. Using nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction analysis, it has been proven that varying the reaction conditions using alkaline hydrolysis of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate makes it possible to successfully synthesize a monohydrate of the target acid, its sodium salt, or 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine. The derivatographic study of the thermal stability of 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid monohydrate has been carried out; based on this study, the optimal conditions completely eliminating the possibility of unwanted decomposition have been proposed for obtaining its anhydrous form. It has been shown that 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine is easily formed during the decarboxylation of not only 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid, but also its sodium salt, which is capable of losing СО2 both in rather soft conditions of boiling in an aqueous solution, and in more rigid conditions of dry heating. The NMR spectra of the compounds synthesized are given; their spatial structure is discussed. To study the biological properties of 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acid and its sodium salt, the experimental model of inflammation caused by subplantar introduction of the carrageenan solution in one of the hind limbs of white rats was used. The anti-inflammatory activity and analgesic effect were assessed by the degree of edema reduction and the ability to affect the pain response compared to the animals of control groups. According to the results of the tests performed, it has been found that after intraperitoneal injection, the substances synthesized demonstrate a moderate anti-inflammatory action and simultaneously increase the pain threshold of the experimental animals very effectively, exceeding Lornoxicam and Diclofenac in a similar dose by their analgesic activity

Reactivity of <i>C</i>‑Amino-1,2,4-triazoles toward Electrophiles: A Combined Computational and Experimental Study of Alkylation by Halogen Alkanes

A combination of computational and experimental methods was used to examine the structure–reactivity relationships in the reactions of <i>C</i>-amino-1<i>H</i>-1,2,4-triazoles with electrophiles. The global nucleophilicity of 3-amino- and 3,5-diamino-1<i>H</i>-1,2,4-triazoles was predicted to be higher than that of 5-amino-1<i>H</i>-1,2,4-triazoles. Fukui functions and molecular electrostatic potential indicate that reactions involving an amino group should occur more easily for the 3-amino- than for the 5-amino-1<i>H</i>-1,2,4-triazoles. Increasing electrophile hardness should increase the probability of attack at the N-4 atom of the triazole ring, whereas increasing softness should enhance the probability of attack at the N-2 atom and 3-NH₂ group. Calculated transition state energies of model S_N2 reactions and experimental studies showed that quaternization of 1-substituted 3-amino- and 3,5-diamino-1<i>H</i>-1,2,4-triazoles by many alkyl halides proceeds with low selectivity and can involve the N-2 and N-4 atoms as well as the 3-NH₂ group as reaction centers. A new method for the selective synthesis of 1,4-disubstituted 3-amino- and 3,5-diamino-1,2,4-triazoles based on quaternization of readily available 1-substituted 3-acetylamino-1,2,4-triazoles with subsequent removal of the acetyl protecting group by acid hydrolysis was developed

The Crystal Structure of N-(1-Arylethyl)-4-methyl- 2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamides as the Factor Determining Biological Activity Thereof

In order to detect new structural and biological patterns in a series of hetaryl-3-carboxylic acid derivatives, the optically pure (S)- and (R)-enantiomers of N-(1-arylethyl)-4-methyl- 2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxamides, their true racemates, and mechanical racemic mixtures have been synthesized in independent ways. The particular features of the 1Н- and 13С-NMR spectra of all synthesized substances, liquid chromato-mass spectrometric behavior thereof under electrospray ionization conditions, and also the results of polarimetric and X-ray diffraction studies have been discussed. Pharmacological screening on a model of carrageenan inflammation has found a clear relationship between the spatial structure of the studied objects and biological activity thereof. Enantiomers with chiral centers having (S)-configuration showed weak inhibition of pain and inflammatory reactions, while their mirror (R)-isomers exhibited very powerful analgesic and antiphlogistic properties under the same conditions, with the level of specific activity exceeding that of Lornoxicam and Diclofenac. Taking obtained data into account, a noticeable decrease in the activity of mechanical racemic mixtures, consisting of one-half of the &ldquo;wrong&rdquo; (S)-enantiomers, is quite natural. The true racemate of N-(1-phenylethyl)-amide proved itself in a similar way, while 4-methoxy-substituted analog thereof stood out against this background with unexpectedly high analgesic and anti-inflammatory activities. A comparative analysis of X-ray diffraction data has found that crystalline and molecular structure of racemic N-[1-(4-methoxyphenyl)ethyl]-4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxamide is completely different from that of the original enantiomers and, moreover, very unusual for racemates. Obviously, it is the factor determining the unique character of the biological effects of the said substance

Synthesis and Regularities of the Structure–Activity Relationship in a Series of <i>N</i>-Pyridyl-4-methyl-2,2-dioxo-1<i>H</i>-2λ⁶,1-benzothiazine-3-carboxamides

According to our quantum and chemical calculations 4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxylic acid imidazolide is theoretically almost as reactive as its 2-carbonyl analog, and it forms the corresponding N-pyridyl-4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides with many aminopyridines. However, in practice, the sulfo group introduces significant changes at times and prevents the acylation of sterically hindered amines. One of these products was 2-amino-6-methylpyridine. Thus, it has been concluded that aminopyridines interact with imidazolide in aromatic form where the target for the initial electrophilic attack is the ring nitrogen. To confirm the structure of all substances synthesized, 1H-NMR spectroscopy and X-ray diffraction analysis were used. From X-ray diffraction data it follows that in the crystalline phase the carbonyl and sulfo group may occupy different positions with respect to the plane of the benzothiazine bicycle: this position may be unilateral, typical for 4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides, versatile, and not yet encountered in compounds of this type. A comparison of these data with the results of the pharmacological screening conducted on the standard model of carrageenan inflammation showed that the N-pyridylamides of the first group demonstrated a direct dependence of their analgesic and anti-inflammatory activity on the mutual arrangement of the planes of the benzothiazine and pyridine fragments. The new molecular conformation of the benzothiazine nucleus provides a sufficiently high level of analgesic (but not anti-inflammatory) properties in all N-pyridylamides of the second group with an extremely weak dependence on the spatial arrangement of the pyridine cycle. All substances presented this article proved themselves in varying degrees as analgesics and antiphlogistics. Moreover, two of them&#8212;N-(5-methylpyridin-2-yl)- and N-(pyridin-3-yl)-4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides&#8212;exceeded the most effective drug of oxicam type Lornoxicam by these indicators

Synthesis, Crystal Structure, and Biological Activity of Ethyl 4-Methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate Polymorphic Forms

Continuing the search for new potential analgesics among the derivatives of 4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxylic acid, the possibility of obtaining its esters by the alkylation of the corresponding sodium salt with iodoethane in dimethyl sulfoxide (DMSO) at room temperature was studied. It was found that under such conditions, together with the oxygen atom of the carboxyl group, a heteroatom of nitrogen is also alkylated. Therefore, the product of the reaction studied is a mixture of ethyl 4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxylate (major) and its 1-ethyl-substituted analog (minor). A simple but very effective method of preparative separation of these compounds was proposed. Moreover, the heterogeneous crystallization from ethanol was revealed to result in a monoclinic polymorphic form of ethyl 4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxylate, while the homogeneous crystallization results in its orthorhombic form. The molecular and crystal structures of both forms were confirmed by X-ray diffraction analysis, and the phase purity by powder diffraction study. The pharmacological tests carried out on the model of a carrageenan edema showed that the screening dose of 20 mg/kg of 1-ethyl-substituted ester and the orthorhombic form of its analog unsubstituted in position 1 exhibited weak anti-inflammatory and moderate analgesic effects. At the same time, the monoclinic form of ethyl 4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxylate appeared to be both a powerful analgesic and an anti-inflammatory agent that exceeded Piroxicam and Meloxicam in the same doses by these indicators. A detailed comparative analysis of the molecular and crystal structures of two polymorphic forms of ethyl 4-methyl-2,2-dioxo-1H-2&lambda;6,1-benzothiazine-3-carboxylate was carried out using quantum chemical calculations of the energies of pairwise interactions between molecules. An explanation of the essential differences of their biological properties based on this was offered

Molecular Conformations and Biological Activity of <i>N</i>-Hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1<i>H</i>-2λ⁶,1-benzothiazine-3-carboxamides

The analysis of our previous studies on the search for synthetic analgesics among N-R-amides of bicyclic hetaryl-3-carboxylic acids has been performed; on its basis N-hetaryl(aryl)-alkyl-4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides have been selected as new study objects. The &#8220;one pot synthesis&#8222; of these compounds, which is simple to perform and at the same time highly effective, has been offered. The method consists in the initial reaction of 4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxylic acid and N,N&#8242;-carbonyldiimidazole in anhydrous N,N-dimethylformamide with the subsequent amidation of imidazolide formed with hetarylalkyl- or benzylamines in the same solvent. The peculiarities of 1H- and 13C-NMR spectra of the substances obtained, as well as their electrospray ionization liquid chromato-mass spectra are discussed. According to the results of the pharmacological tests carried out on the model of carrageenan inflammation it has been found that all without exception N-hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides demonstrate the statistically significant analgesic and anti-inflammatory properties. Among the substances presented in this article analgesics and antiphlogistics, which increase the pain threshold and suppress the inflammatory response more effectively than Lornoxicam and Diclofenac in the same doses, have been identified. The molecular and crystal structures of a large group of the substances synthesized have been studied by X-ray diffraction analysis. Comparison of these data with the results of biological tests has revealed the fact of excellent correlation between the molecular conformations of N-hetaryl(aryl)alkyl-4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxamides recorded in the crystal and the potency of their analgesic effect. N-Thiophen-2-ylmethyl- and N-4-methoxybenzyl-amides of 4-methyl-2,2-dioxo-1H-2&#955;6,1-benzothiazine-3-carboxylic acid has shown a high analgesic and anti-inflammatory effect, therefore, they deserve more careful research