The immunopotentiating properties of BCG vaccine strain antigen conjugated with betulin derivatives have been evaluated. The experiments were carried out on agouti guinea pigs (
n
= 20). The animals ...of the experimental groups (
n
= 5) were immunized with the following antituberculosis drugs: group 1, with antigens of the BCG vaccine strain conjugated with betulinic acid; group 2, with BCG antigens conjugated with betulonic acid; and group 3, with the BCG vaccine. The animals of the control group (
n
= 5) were injected with a saline solution. All the animals were infected with a virulent culture of
Mycobacterium bovis
(strain 8) on day 30 after the administration of antituberculosis drugs. The blood sampling for the assessment of the immune status was conducted on day 30 after the administration of drugs and day 30 after the infection with
M. bovis
. The designed conjugates were found to display immunopotentiating activity characterized by a 1.7–3.8-fold increase in the number of immunocompetent cells and an increase in the neutrophil functional activity observed to a greater degree in the guinea pig group 2. After infection with
M. bovis
some key parameters of the immune system, such as a T-lymphocyte count and the activity of enzymatic (myeloperoxidase) and nonenzymatic (cationic proteins) bactericidal systems of neutrophilic granulocytes significantly increased in groups 2 and 3, which implied the highest antituberculosis activity of the agents administered to these animals. The guinea pigs were euthanized 45 days after the infection with
M. bovis
. The next pathoanatomical experiments proved that the vaccine strain conjugates with betulonic acid and the BCG vaccine induced marked resistance against the pathogenic mycobacteria. The protection indexes for these agents were approximately the same and achieved 66 and 71%, respectively.
Computational study of some details of the cyclization reaction between 3,5-diacetyl-2,6-dimethylpyridine and salicylic aldehyde in an acidic medium was performed by the DFT RB3LYP/6-31G method using ...the Gaussian-2016 software package. It was shown that protonation of the pyridine nitrogen atom leads to a significant increase in the charge of the hydrogen atom of the 2-methyl group of pyridine and the methyl acetyl group. This leads to the growth of the methyl group CH-acidity and enolization of the acetyl group. It was also found that the protonated tautomeric enol form of 3,5-diacetyl-2,6-dimethylpyridine gives a stable pre-reaction complex with salicylic aldehyde due to the formation of three hydrogen bonds. The formation of this pre-reaction complex, apparently, leads to the implementation of the Knoevenagel reaction, instead of the alternative possible Claisen–Schmidt reaction of salicylic aldehyde at the acetyl group of pyridine. The possible biological activity of the previously obtained cyclization products was evaluated by molecular docking using the AutoDock Vina software. Some cyclization products showed higher values of the binding affinity with the selected target proteins in comparison with the known antiviral drugs Nevirapine and Favipiravir. The results obtained confirm the correctness of the proposed cyclization mechanism between 3,5-diacetyl-2,6-dimethylpyridine and salicylic aldehyde. This also makes it possible to assess the prospects of previously obtained derivatives of epoxybenzo7,8oxocino4,3-
b
pyridine as synthetic analogs of natural integrastatins A, B for further synthesis and study of their antiviral activity.
Processing Modes for Nitinol with Added Iron Splavskiy, I. S.; Kulakov, O. I.
Journal of machinery manufacture and reliability,
12/2022, Letnik:
51, Številka:
8
Journal Article
Recenzirano
The results of study of an alloy with the shape memory effect, alloyed with iron, in relation to the designs of nodes for extreme operating conditions, are presented. The temperature and deformation ...modes of manufacturing semi-finished products from an alloy with the shape memory effect are given.
Heat and mass transfer and gas distribution in a nonequilibrium steam-water volume with a phase separation level containing a noncondensable gas are considered. These processes relate primarily to ...the steam–gas pressurizer (SGP) of the integral reactor and determine the behavior of the SGP in normal and emergency modes. Similar processes occur in a pressurized water reactor and in a containment volume at the final stage of emergency regimes with loss of coolant. For small-power reactors of the RITM-200 type with a gas pressurizer, it is necessary to take into account the phenomena associated with the behavior of noncondensable gases. A brief description is given of the GARRIC 2.2 computer program for calculating the distribution of noncondensable gases in the primary circuit and the characteristics of the SGP of a pressurized water reactor of an integral layout. The description of the processes of heat and mass transfer and gas distribution is based on the results of experiments carried out on SGP models in a wide range of parameters and gas contents. Calculation of mass transfer, including surface evaporation and steam condensation, and gas transfer on the surface is carried out using the analogy model of heat and mass transfer under conditions of natural convection of the medium. The results of the verification of the GARRIC 2.2 program on the experimental data obtained in the study of vapor condensation on the walls, evaporation on the free surface of water, and gas distribution in the steam–gas volume at full-scale parameters are presented. The GARRIC 2.2 program was certified by Rostekhnadzor in 2014.
The optimal conditions for the oxidation of the methylene group in 4-ethyl-3-methylcinnoline to the corresponding ketone, 3-methyl-4-acetylcinnoline, were selected. It was shown that preliminary ...deposition of 4-ethyl-3-methylcinnoline on some inorganic substrates has a significant effect both on the selectivity of the oxidation of only the methylene group and on a high degree of conversion to the target product.
On the basis of 4-(thien-2-yl)-3-aminopyridine-2(1
H
)-one, the corresponding chloroacetamide and condensed 1
H
-pyrido2,3
-b
1,4oxazine-2(3H)-one were synthesized by the reaction of acylation with ...chloroacetyl chloride. Thioureide derivatives of 3-aminopyridine-2(1
H
)-one were obtained by reactions with a number of isothiocyanates. It was shown that the carbamothionylmethacrylamide derivative cyclizes rather easily into substituted 1,3-thiazine. Molecular docking of synthesized derivatives for antithrombotic activity was carried out, which showed that the presence of a thiourea fragment in the pyridone core leads to an increase in affinity for the selected protein. The hemorheological study of the compounds using the in vitro model of the increased blood viscosity syndrome also showed activity at the level of the reference drug pentoxifylline.
A three-component reaction of 3,5-diacetyl-2,6-dimethylpyridine,
p
-
N
-dimethylaminobenzaldehyde and phenylhydrazine in the presence of KOH in ethanol gave the condensation product of two
p-N
...-dimethylaminobenzaldehyde and phenylhydrazine molecules, namely bis(biarylhydrazone). Structure of the obtained derivative was proved by the
1
H and
13
C NMR spectroscopy and X-ray diffraction analysis data. It was shown that the bis(biarylhydrazone) derivative has high antiradical and cytoprotective activity.
As a result of the oxidative aromatization of 5-nitro-1,4-dihydropyridines with hydrogen peroxide in a dioxane solution, previously unreported in the literature on the 5-(3-)nitropyridines ...derivatives radical
ipso
-substitution reaction of the nitro group with hydrogen was discovered. Upon careful examination of the nitro group ipso-substitution reaction, the formation of several by-products such as oxadiaziridine
N
-oxide, diazene and benzamide, associated with the oxidative-reductive combination of two molecules of 5-nitropyridine and its oxidative destruction, was observed. A possible mechanism for the radical
ipso
-substitution reaction of the nitro group with hydrogen has been proposed. It was found that the presence of an alkyl or aryl substituent at the 4-position of 5-nitropyridine derivatives does not lead to the ipso-substitution of nitro group with hydrogen. Molecular docking of several by-products’ structures to the presumed antimicrobial activity revealed higher binding affinity values (kcal/mol) with selected protein receptors ranging from –7.7 to –11.7 kcal/mol compared to the antibiotic ciprofloxacin, making them promising candidates for further investigation of potential antimicrobial activity.
The Klyuchevskoy group of volcanoes (KGV) in Kamchatka includes three presently active volcanoes (Klyuchevskoy, Bezymianny, and Tolbachik) located close together in an area of approximately ...50 × 80 km. These three volcanoes have completely different compositions and eruption styles from each other. We have analyzed new data recorded by a temporary seismic network consisting of 22 seismic stations operated within the area of Tolbachik in 2014–2015 in conjunction with the data from the permanent network and the temporary PIRE network deployed at the Bezymianny volcano in 2009. The arrival times of the P and S waves were inverted using a local earthquake tomography algorithm to derive 3‐D seismic models of the crust beneath the KGV as well as accurate seismicity locations. High‐resolution structures beneath the Tolbachik volcanic complex were identified for the first time in this study. The tomography results reveal three different types of feeding system for the main KGV volcanoes. The basaltic lavas of the Klyuchevskoy volcano are supplied directly from a reservoir at a depth of 25–30 km through a nearly vertical pipe‐shaped conduit. The explosive Bezymianny volcano is fed through a dispersed system of crustal reservoirs where a lighter felsic material separates from the mafic component and ascends to the upper crust to form andesitic magma sources. For Tolbachik, low‐viscosity volatile‐saturated basalts ascend from two deep reservoirs following a system of fractures in the crust associated with the intersections of regional faults.
Plain Language Summary
The Klyuchevskoy group of volcanoes (KGV) in Kamchatka includes three presently active volcanoes (Klyuchevskoy, Bezymianny, and Tolbachik) located close together in an area of approximately 50 × 80 km. These three volcanoes are among the most active volcanoes in the world, and they have completely different compositions and eruption styles from each other. We have analyzed new data recorded by a temporary seismic network consisting of 22 seismic stations installed within the area of Tolbachik in 2014–2015 in harsh natural conditions. Based on these data, we have derived high‐resolution structures beneath the Tolbachik volcanic complex and surrounding areas. The tomography results reveal three different types of feeding system for the main KGV volcanoes. The basaltic lavas of the Klyuchevskoy volcano are supplied directly from a reservoir at a depth of 25–30 km through a nearly vertical pipe‐shaped conduit. The explosive Bezymianny volcano is fed through a dispersed system of crustal reservoirs where a lighter felsic material separates from the mafic component and ascends to the upper crust to form andesitic magma sources. For Tolbachik, low‐viscosity volatile‐saturated basalts ascend from two deep reservoirs following a system of fractures in the crust associated with the intersections of regional faults.
Key Points
A new crustal seismic model is constructed for Tolbachik and adjacent volcanoes
Seismicity beneath Klyuchevskoy reflects a straight conduit that brings magma directly from the mantle
The Bezymianny volcano is fed through separating felsic magma and volatiles from midcrustal sources
