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Resume. The search for new drugs with cytoprotective and anti-ischemic activity is an urgent task of modern pharmacology. These properties are necessary for the complex protection of renal parenchyma during organ preservation operations (renal resection), most often carried out in conditions of thermal ischemia. Only the combined use of modern highly effective drugs and the skill of an operating surgeon can prevent the development of acute renal injury (AKI) due to pinching of renal vessels. The aim of this study was to investigate the nephroprotective effects of a combination of a peptide mimicking the a-helix B of erythropoietin (pHBSP) and infliximab in ischemic reperfusion damage to the kidneys. Methods. The experiment was conducted on 50 white laboratory male Wistar rats weighing 280-320 g. Animals were injected with a peptide mimicking the a-helix B of erythropoietin (pHBSP) and infliximab. Under anesthesia, atraumatic vascular clamps were applied to the left renal pedicle for 40 minutes, nephrectomy on the right. Functional samples and laboratory tests were performed 5 minutes and 72 hours after reperfusion. Results. As a result of the study, it was shown that using a combination of the peptide simulating a-helix B erythropoietin (pHBSP) and infliximab in ischemic-reperfusion kidney injury showed significantly more pronounced nephroprotective effects than using the peptide mimicking a-helix B erythropoietin or infliximab in the mono mode. Conclusion.The results of the study show the promise of combined use of peptide simulating a-helix B erythropoietin (pHBSP) and infliximab in order to correct ischemic-reperfusion kidney injuries.

The search for drugs that can prevent the development of acute renal injury (ARI) is one of the main tasks of modern pharmacology. Methods.The experiment was carried out in 50 white Wistar male laboratory rats weighing 280-320 g. The animals were injected with a peptide mimicking the spatial structure of the B erythropoietin chain (pHBSP) and infliximab. Results.The combined use of a peptide mimicking the spatial structure of the B erythropoietin chain (pHBSP) and infliximab before renal ischemia-reperfusion injury is more effective than the nephroprotective properties of the above substances when it is selectively used. Conclusion. According to the results of the study, we can talk about the prospects of the combined use of the peptide mimicking the spatial structure of the B erythropoietin chain (pHBSP) and infliximab in order to correct renal ischemia-reperfusion injury.

Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein.

Стаття присвячена аналізу трудового договору як форми реалізації права на працю та підстави (юридичного факту) виникнення трудових правовідносин. Розглянуто особливості процедури укладення трудового договору та його оформлення залежно від трудової функції, яку буде виконувати працівник. Обґрунтовано висновок, що підставою виникнення трудових правовідносин є трудовий договір, незалежно від його форми і виду. Однією з обов’язкових умов трудового договору, без якої трудовий договір не може вважатися укладеним, є вказівка про трудову функцію працівника відповідно до Класифікатора професій. Оформлення трудового договору відбувається шляхом видачі наказу, у якому зазначається посада, на яку призначається працівник, або робота, яку він буде виконувати The article deals with the analysis of the employment contract as a form of realization of the right to work and the legal fact of labor legal relations emergence. Based on the analysis of the norms of the Labor Code of Ukraine, the author draws the conclusion about the need to distinguish between concluding the contract of employment and its execution. The conclusion of an employment contract may occur as a result of an agreement to perform some work, the actual admission of the employee to work, or it may imply the presence of the legal procedures (eg competitive selection, election for the position, etc.). The employment contract is executed by issuing an order or instruction on hiring or appointment to the position. The article substantiates that the basis of employment is an employment contract, regardless of its form (written or oral) and the type (contract, an employment contract for part-time work, an employment contract for temporary or seasonal work). One of the mandatory conditions of the contract of employment is an indication of the employee's job functions in accordance with the Classifier of Occupations. Without it the contract of employment cannot be considered as such that has been concluded. The employment contract is executed by issuing an order stating the position to which the employee is appointed or the work he will perform.

An isotope-geochronological study for a number of young volcanic localities in the eastern part of Balkaria (North Caucasus, Russia), referred to the Neogene–Quaternary stage in the evolution of the Greater Caucasus by previous researchers, was carried out. The results of the K–Ar dating obtained have proved for the first time that volcanic activity was intense in the Late Cenozoic within the territory of modern Eastern Balkaria. It has been established that the young igneous rocks of the Pliocene (4.7–4.0 Ma) Tsana Formation with various compositions (basaltic trachyandesite, dacite, and granodiorite-porphyry) are the most common in the considered region. The area of presence of the rocks of the Tsana Formation was specified within the Russian territory of the North Caucasus. Based on the new isotopic data, the territory that is prospective for exploration of Au–As–Sb–Sn–Mo deposits often associated with young plutonic bodies of potentially ore-bearing Tsana Formation was localized. A new locus of Late Quaternary magmatism where the andesite lava flow was formed ~800–700 ka in the paleovalley of the Udursu River (near the foot of Mt. Cheget-Dzhora) was identified within the Greater Caucasus.

New data are presented on the quartz porphyry dikes of the Salmi batholith belonging to anorthosite–rapakivi granite rock complexes. The relationships of various igneous rocks of the Salmi batholith and metasomatites were determined along with the isotopic U–Pb age by the LA–ICP–MS technique and the temperature of zircon formation by the Ti content.

The results of petrological-geochemical and isotope-geochemical studies of the Late Pleistocene-Holocene lavas of the Kazbek Neovolcanic Center, one of the largest centers of youngest magmatism in the Greater Caucasus, are presented. It has been established that the volcanic rocks of the Kazbek center arise a continuous compositional series basaltic (trachy-)andesites(trachy-)andesitesdacites with a predominance of calc-alkaline intermediate and moderately-acid lavas. The obtained results indicate that the processes of fractional crystallization and mixing of melts had a leading role in the petrogenesis of the rocks. The crustal assimilation was of limited importance; its influence is noticeable only in the rocks of the earliest and late pulses of magmatic activity within the Kazbek center. The common crustal lithologies participated in the assimilation were presented by metamorphosed Jurassic sediments (mainly shales and sandstones), forming the foot of the Kazbek center, and Mesozoic mafic metamorphosed volcanites very rarely. The specific features of AFC processes during the development of the studied magmatic system (including the presence of noticeable amount of water in the melt, the leading role of Amp in the cumulus and the absence of Pl fractionation) led to the appearance of dacitic lavas with geochemical signs of adakites as an evolutional end-member. The volcanic rocks of the Kazbek center are derived from trachybasalt magmas, the source of which was presented by the mantle reservoir of OIB-type. Recent and previously published results of studies of the Neogene-Quaternary magmatism manifested within the Greater Caucasus show that the main petrological and geochemical characteristics of this regional mantle reservoir remained constant from the end of the Miocene to the present time.

The paper reports the isotope-geochronological and petrological-geochemical studies of the Pliocene moderately-acid volcanism of the Akhalkalaki Plateau in the central part of the Lesser Caucasus (Javakheti highland, Georgia). K-Ar dating showed that young dacitic lavas and pyroclastic rocks were formed in the Mid-Pliocene (3.28 ± 0.10 Ma) in relation with the explosive–effusive eruptions of small composite volcanic cones and formation of minor extrusive domes confined mainly to the eastern margin of the region. Isotope-geochronological data in the combination with results of structural drilling indicate that the considered short-term pulse of the volcanic activity occurred during a short gap between two phases of the Pliocene–Early Pleistocene mafic magmatism widespread within the Akhalkalaki plateau. The studied Pliocene dacites were erupted at the post-collisional stage of the evolution of the Lesser Caucasus, but bear petrological-geochemical affinity of adakitic series. They are characterized by the steady presence of amphibole phenocrysts, the elevated contents of Sr, Ba, LILE and the lowered contents of Y, Nb, Ta, and HREE, and have depleted Sr isotopic composition (87Sr/86Sr < 0.7045). Analysis of petrogenetic models earlier proposed to explain the generation of adakite-like magmas in the modern collision zones showed that the origin of the Pliocene dacitic lavas of the Akhlkalaki plateau is best described by the crystallization differentiation of watersaturated calc-alkaline basaltic melts with removal of common mafic rock-forming minerals (first of all, amphibole and pyroxene) and accessory phases (apatite, titanite, Ti-magnetite) as cumulus minerals. Crustal assimilation of evolved magmas only insignificantly contributed to the petrogenesis of the dacites.

Purpose To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. Material and methods At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier’s performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. Results In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77–0.93 (sensitivity 0.91, 95% CI 0.81–0.97; specificity 0.71, 95% CI 0.44–0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72–0.9), 0.81 for [18F]-FET-PET (95% CI 0.7–0.89), and 0.81 for expert consensus (95% CI 0.7–0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. Conclusion Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-021-05427-8.

The article describes arginase’s role in pathogenesis of endothelial dysfunction and a number of cardio-vascular diseases. Arginase catalyzes the hydrolysis of L-arginine, the substrate for nitric oxide synthesis, to L-ornithine and urea. Two isoforms of arginase were found in the human organism. Arginase I is located in the cells cytoplasm and is predominantly expressed in the liver. Arginase II is a mitochondrial protein that is expressed in the kidney, prostatic gland and vascular wall. Arginase II hydrolyzes L-arginine, thereby reducing the synthesis of nitric oxide and leading to the development of endothelial dysfunction and a number of cardio-vascular disorders. Arginase is a promising pharmacological target in the treatment of endothelial dysfunction and a number of cardio-vascular diseases, though the development of highly-selective arginase II inhibitors is still a difficult task.

Aim. To study the antidiarrhoeal activity of montmorillonite-based enterosorbent on the model of serotonin-induced diarrhea.Materials and methods. The study was performed on laboratory mice of both genders, acute diarrhea was induced by intraperitoneal injection of serotonin hydrochloride at a dose of 0.32 mg/kg, enterosorbent as an aqueous suspension was administered orally in a wide range of doses 30 minutes prior to serotonin administration. Within 4 hours, the time of diarrhea onset, the number of defecations, the fluid content in the fecal masses was considered. Morphological examination of the small intestine was carried out. Results. The administration of serotonin led to the development of diarrhea in 100% of animals in 12,8±1,2 minutes, the number of defecations increased 2,5 times compared to intact animals and was 19,5±0,5 times within 4 hours, the fecal masses were predominantly wet and liquid. The use of enterosorbent under the Crim_04 cipher in the maximum dose led to a delay in the development of diarrhea to 73,6±4,1 minutes, a reduction in the number of defecations to 9,4±0,1 and a significant inspissation of stool. The antidiarrhoeal effect of enterosorbent was confirmed morphologically.Conclusions. Montmorillonite-based enterosorbent under the laboratory cipher Crim_04 has a dose-dependent antidiarrhoeal activity in the modeling of serotonin-induced diarrhea.

The PET radioligand [11C]PBR28 binds to the translocator protein (TSPO), a marker of brain immune activation. We examined the reproducibility of [11C]PBR28 binding in healthy subjects with quantification on a regional and voxel-by-voxel basis. In addition, we performed a preliminary analysis of diurnal changes in TSPO availability. Twelve subjects were examined using a high-resolution research tomograph and [11C]PBR28, six in the morning and afternoon of the same day, and six in the morning on two separate days. Regional volumes of distribution (V T) were derived using a region-of-interest based two-tissue compartmental analysis (2TCM), as well as a parametric approach. Metabolite-corrected arterial plasma was used as input function. For the whole sample, the mean absolute variability in V T in the grey matter (GM) was 18.3 ± 12.7 %. Intraclass correlation coefficients in GM regions ranged from 0.90 to 0.94. Reducing the time of analysis from 91 to 63 min yielded a variability of 16.9 ± 14.9 %. There was a strong correlation between the parametric and 2TCM-derived GM values (r = 0.99). A significant increase in GM V T was observed between the morning and afternoon examinations when using secondary methods of quantification (p = 0.028). In the subjects examined at the same time of the day, the absolute variability was 15.9 ± 12.2 % for the 91-min 2TCM data. V T of [11C]PBR28 binding showed medium reproducibility and high reliability in GM regions. Our findings support the use of parametric approaches for determining [11C]PBR28 V T values, and indicate that the acquisition time could be shortened. Diurnal changes in TSPO binding in the brain may be a potential confounder in clinical studies and should be investigated further.

New isotope-geochronological data (K-Ar, Rb-Sr) provide tight geochronological constraints on the history of Late Cenozoic magmatism on the southern slope of the Greater Caucasus. Several previously unknown, rhyodacite intrusive bodies with an emplacement age of 6.9 ± 0.3 Ma (Late Miocene) are reported from the Kakheti-Lechkhumi regional fault zone in the Kvemo Svaneti-Racha area. Therefore, a pulse of acid intrusive magmatism took place in a period previously considered amagmatic in the Greater Caucasus. The petrological, geochemical, and isotopic data suggest that these rhyodacites are produced by crystallization differentiation of mantle-derived magmas, which are similar in composition to Miocene mafic lavas that erupted a few hundred thousand years later in the adjacent Central Georgian neovolcanic area. The presented results allow the conclusion that the volcanic activity within the Central Georgian neovolcanic area occurred at 7.2–6.0 Ma in two discrete pulses: (1) the emplacement of acid intrusions and (2) the eruption of trachybasaltic lavas. The emplacement of rhyodacite intrusions in the Kvemo Svaneti-Racha area marked the first pulse of young magmatism on the southern slope of the Main Caucasus range and simultaneously represented the second magmatic pulse (after granitoid magmatism of the Caucasian Mineral Waters region) within the entire Greater Caucasus.

Study of epochs of tectonomagmatic activity of the Earth in different parts of the planet and under various geodynamic environments suggests as one of the main tasks of such investigations establishment of their age, duration, evolution dynamics, spatial–age regularities of volcanic focus migration, and other characteristics allowing one to reconstruct the history of magma gen� esis for concrete regions on the level of individual time lags of the geochronological scale. In this paper we discuss the results of the study of geochronology of Miocene volcanism in the northern part of neovolcanic province in the Lesser Caucasus, which allows us to determine the time of beginning and total duration of the Late Cenozoic epoch of tec� tonomagmatic activization in this sector of the Cauca� sian–Anatolian segment of the Alpine foldbelt. Products of the earliest impulses of Neogene– Quaternary volcanism within the northern end of the mountain system of the Lesser Caucasus, as is evident from the results of geological and stratigraphic investi� gations [1], are abundant in the upper reaches of the Kura River on its left bank, where they form the exten� sive (60 × 30 km) Erusheti volcanic highland on the territory of Georgia and Turkey (Fig. 1). They are united in the Goderdzi Formation in the Georgian part of the region. The lower parts of sections of the formation are composed of the pyroclastic series with a thickness of up to 700 m represented by welded and loose layered tuff, breccia, and agglutinate, in which thin lava flows of dacitic or more basic composition are sometimes observed. Numerous volcanic edifices (Gumbati, Shalosheti, Digra, and others) significantly destroyed and smoothed by erosion, their dacite lava flows forming a sheet with a thickness of up to several hundred meters, and overlying pyroclastic formations on most of the region are located on the surface of the Erusheti highland. The maximal heights within the highland reach 3000 m (on the territory of Turkey); its basement is entirely composed of sedimentary and volcanogenic series of Eocene age. Effusive rocks of the Goderdzi Suite in the east in valleys of the Kura River and its right tributary Paravani are overlain by mainly basic Pliocene lavas of the Dzhavakheti high� land (3.7–1.6 Ma [2]) and further, in the latitudinal direction most likely entirely thin out in sections within the area of western ends of the Samsari ridge, where Quaternary lavas occur directly on rocks of the Early Cenozoic–Mesozoic basement [3]. The available concepts on the age of rocks of the Goderdzi Formation were mainly based on the results of investigations of plant and fossil remains in horizons of diatomic clays, which are known and were previ� ously mined in some locations at the bottom of the young effusive series in the Erusheti Highland [1, 4]. These data allowed us to establish the possible age range of the formation of pyroclastic rocks and lavas of the formation as Late Miocene–Early Pliocene. !"# !"$ !"% !"" !"& $# $$ $% !"’ !"( !&) !&* !&! + , .

Forecast of possible scenarios of eruptive activityfor volcanic centers and individual volcanoes as well asthe type and character of their future eruptions is animportant aspect of investigations of modern (Quaternary) magmatism of the Earth. Prognostic reconstructions of this type are impossible without analysis oftendencies in the development of volcanic centers anddetermination of the main time characteristics ofmagmatic activity occurred inside them. The Northern Caucasus is the only region in European Russiawhere modern magmatism was manifested, althoughonly to a small extent. Magmatic activity in the Anthropogene occurred there exclusively within the Elbrusneovolcanic center in the southern part of which theElbrus, one of the largest Quaternary volcanoes of theNorthern Eurasia, was formed lesser than 250 ka [1–3].Quaternary volcanism of the Elbrus center started~950–900 ka [4] with eruptions of three lava volcanoes (Tyzyl, Tashlysyrt, and Syltran) located withinthe linear submeridional zone at the Baksan andMalka interfluves. The regular decrease of SiO

One of the well-known areas with youngest volcanism in the Lesser Caucasus is located in the vicinity of the Borzhomi City (central Georgia) famous by mineral water springs. This relatively small area hosts four volcanoes (Tsitelidabadzveli, Tsikhisdzhvari, Mukhera, and Sargavi), which yielded extended (from 2 to 13 km long) flows of andesite to, subordinate, basaltic andesite lavas (figure). In scientific works dedicated to different aspects of Neogene‐Quaternary magmatism of the Caucasus region, manifestations of basaltic andesite‐andesite volcanism in the examined part of the Lesser Caucasus mountainous system are usually united into the Bakuriani‐Borzhomi neovolcanic area [1 and others]. It is composed of Upper Cretaceous carbonate bands, Paleocene‐Lower Eocene terrigenous rocks of the Borzhomi series, and Middle Eocene‐Oligocene volcano-sedimentary sequences. Young lava flows a few tens of meters thick known in this area lie with stratigraphic and angular unconformities upon the Paleogene basement spreading over significant part of studied territory (Fig. 1). It should be noted that, according to the recent tectonic map of Georgia [2], magmatic activity in the Bakuriani‐Borhomi area was concentrated in the Adzharia‐Trialeti zone of the Lesser Caucasus fold system with volcanoes confined to the linear near-latitudinal Bakuriani abyssal fault zone at its intersection with the meridional Samsari Fault. Tsitelidabadzveli Volcano (2320 m) is located on the northern slope of the Trialeti Range 12 km south of Borzhomi. It represents an oval meridionally extended edifice up to 100 m high composed of pyroclastics (scoria, breccia, lapillis) with subordinate interbeds of dark gray and reddish lavas. Basaltic andesite lava flows erupted by this volcano fill a spacious depression 8 × 6 km in size and form the Dabadzveli Plateau, the surface of which is located at altitudes of 2100 to 1600 m and is slightly inclined in the northern direction toward the Kura River valley. Basaltic andesites of the Tsitelidabadzveli Volcano (samples YUG-156 from the volcano cone and YUG-157 from lavas of the Dabadzveli Plateau) represent massive to vesicular porphyric to subordinate aphyric rocks. Phenocrysts in porphyric varieties are dominated by plagioclase (labradorite) and clinopyroxene (augite) accompanied by subordinate orthopyroxene (hypersthene) and olivine. Tsikhisdzhvari Volcano (1818 m) is located 2.5 km

The products of volcanic activity from the Kutaisi area and Guria (western Georgia) were studied in terms of isotope geochronology to determine the age of rocks and to confirm their attribution to Cenozoic formations. The results obtained show that the erupted rocks in the Kutaisi area were formed during the three pulses of Mesozoic volcanic activity: the Bajocian, Kimmeridgian-Tithonian, and Turonian-Santonian. It was shown that no displays of Late Cenozoic volcanism occurred in this region of the western Georgia. Because of this, its inclusion into the Central Georgian neovolcanic province, earlier supposed, seems to be improper. By the data of isotope geochronology, Guria is the only region of western Georgia where volcanic activity occurred in post-Paleogene period. Two pulses of young volcanism were revealed: of about 15.5 and 9-7.5 My. The former was related to the introduction of syenite intrusion, and the latter, to subaqueous exudation of subalka- line Neogene lavas. All the outcrops of Neogene rocks we found and dated in Guria fit within the well-pro- nounced sublatitudinal linear band which probably represents the occurrence in the Middle Miocene of a local zone of extension appearing under conditions of total compression during the collision of the Eurasian and Ara- bian lithospheric plates.

The paper reports newly obtained stratigraphic, petrographic, and isotope-geochronological data on modern moderately acid lavas from the Keli Highland at the Greater Caucasus and presents a geological map of the territory, in which 35 volcanoes active in Late Quaternary time were documented by the authors. The total duration of volcanic activity at the highland was estimated at 250 ka. The volcanic activity was discrete and occurred in three phases: Middle Neopleistocene (245-170 ka), Late Neopleistocene (135-70 ka), and Late Neopleistocene-Holocene (

Transport in a turbulent vortex ring is considered; the mass of a passive impurity transported by the vortex is found as a function of distance traveled via a formula that agrees closely with experiment. A method is indicated for filling the part of the vortex that transports the impurity without loss. The effects of the following factors on the transport have been examined: initial Reynolds number, roughness in walls of the exit hole, and density difference between the solution and the medium. The transport of aerosols and suspended particles by vortex rings is considered. Two methods of transport measurement are compared.