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INTRODUCTION: Sepsis remains an actual problem of modern medicine. Among other treatment options, timely prescribed optimal nutritional-metabolic support is one of the priority methods of intensive treatment for this category of patients. OBJECTIVE: To study the severity of metabolic dysfunction in sepsis and determine the parameters of optimal substrate supply for this category of patients. MATERIALS AND METHODS: The study included 166 patients with sepsis. We studied the severity of systemic metabolic dysfunction and the impact of various options for energy and protein supply on the course of the disease and its outcome. Energy expenditure and the severity of the catabolic reaction of the body were studied by dynamic evaluation of indicators of indirect calorimetry, actual losses of nitrogen and nitrogen balance. RESULTS: Actual energy expenditure in sepsis reaches its maximum values by the 5–6th day of the disease (33.5 ± 1.8 kcal/kg/day or 2366 ± 126 kcal/day). The average energy consumption in sepsis is 2226 ± 96 kcal/day or 30.9 ± 1.4 kcal/kg/day. Energy supply in sepsis less than 25 kcal/kg/day leads to a significant increase in mortality. Protein losses in sepsis reach their maximum values by the 5–6th day of the disease (1.93 ± 0.12 g/kg/day). The average loss of protein in sepsis is 1.68 ± 0.06 g/kg/day. Protein provision of this category of patients with more than 1.5 g/kg/day contributes to a significant decrease in mortality, relative to patients receiving less protein per day. CONCLUSIONS: Energy supply in the range of 25–35 kcal/kg/day, as well as protein supply of more than 1.5 g/kg/day, significantly contribute to better survival of patients with sepsis.

The article deals with an urgent issue related to the establishment of types of enforcement of obligations to pay taxes and fees. Legal aspects and features of each type of security are also analyzed

Based on the author’s fieldwork in 1976–2016 and herbarium funds from the river Chulyshman, stored inthe Central Chernozem Reserve, the first part of the information (Magnoliophyta: Liliopsida, not including the PoaceaeBarnhart family) is given on new and rare species of vascular plants for this territory; 5 species are indicated for the firsttime for the Altai nature reserve.

Results of the first lichenological study of the manmade mine dumps of the Michailovsky mining and processing plant including nature and urban surroundings (Zheleznogorsky district, Kursk region) are presented. Materials were collected by the route method during 2017 and 2019-2020, cameral treatment was carried out using generally accepted lichenological methods. Identified specimens are stored in the herbaria of the Prof. V. V. Alekhin Central Chernozem Natural biosphere reserve and the Station of Young Naturalists in Zheleznogorsk. The studied lichen biota includes 88 species (mainly macro-lichens, due to the collection method) from 38 genera, 18 families. The prevailing metal tolerant species are: terricolous Cladonia fimbriata, C. coniocraea, epigeic C. rei, C. mitis, C. cornuta, C. furcata, C. phyllophora and C. gracilis, epiphyticepixylous Evernia prunastri, Parmelia sulcata, Xanthoria parietina, Hypogymnia physodes and Physcia adscendens. An annotated listing of species, rare to various extent, has been made. It includes 4 new spesies for the Central Chernozem region (Cladonia cervicornis, Dibaeis baeomyces, Usnea dasopoga, U. lapponica); 5 new ones for the Kursk region (Bryoria fuscescens, Cladonia carneola, C. deformis, Melanohalea septentrionalis, Peltigera extenuata); 6 species included into Red Data Book of Kursk region (Cladonia subrangiformis, C. subulata, Peltigera praetextata, Platismatia glauca, Pseudevernia furfuracea and Usnea subfloridana); 5 more are rare for the region or more vast territories (Acarospora veronensis, Protoparmeliopsis muralis, Ramalina pollinaria, Trapelia coarctata, Usnea hirta). A large massive of a considerable amount of rare species in the technogenic landscapes seems to be determined by several causes: presence of large outcrops of a substrate rare for the region and Central Chernozem Region (ferruginous sandstone); weak competition from vascular plants on the poor and metal-enriched soils and subsoils; the botanical-geographic position of the territory; the specifics of the local environmental pollution, represented mainly by “acidic” pollutants and metal particles. The association of the regionally rare fruticose and foliose epiphytes from the ecological group of acidophiles to the birch plantations in the studied technogenic landscapes was noted. Some measures are proposed for the protection of identified rare species of lichens.

Based on the analysis of 91 geobotanical descriptions with Stipa pulcherrima C. Koch from three reservesof Russia (Tigireksky, Belogorye, Central Chernozem), the species is confined to certain habitats. The number ofStipa pulcherrima individuals in the areas of the reserves is reported. Species of vascular plants that are often found incommunities with Stipa pulcherrima are given.

Belgorod oblast is a region of ancient economic development with the highest level of agricultural land use in Russia and, accordingly, the highest level of anthropogenic transformation of zonal vegetation and soils (chernozems). Despite all of the efforts of recent years to improve the conservation of territorial nature in the region, all categories of specially protected territories make up only 1.8%, which is one of the lowest rates in the Russian Federation. Steppe plots occupy less than 10% of the area of all protected areas, i.e., 0.2% of the region’s area, which cannot serve as the basis for the conservation of steppe biodiversity and the formation of the ecological framework of the region, where the zonal type of vegetation is steppes. The article provides a historical analysis of the transformation of the region’s steppes, the results of an inventory with remote sensing methods of the preserved sections of the steppes, assessment of the potential of their flora for the development of restoration succession, and the effectiveness for preservation of the steppe biodiversity of the regional network of specially protected areas and the formation of an ecological framework. It is shown that more than 700 identified sites with preserved steppe vegetation (about 47 000 ha) are small-contoured and fragmented and are located on the nonarable and strongly eroded slopes of draws and narrows. Without special events, they are not able to become the basis of the ecological framework. Approaches and methods of stimulating the restoration of the steppes on post-agrogenic and technogenic lands of the region are proposed.

The article deals with the issues of complex technology and equipment for refining and casting steel and alloys in the foundry industry. Solutions are given that make it possible to guarantee a reduction in nonmetallic inclusions in the melt, as well as to solve a number of other related problems of foundry production, such as the introduction of a bottom blowing melt system with an inert gas; the introduction of protection of the metal stream from secondary oxidation; lining the arch of an electric arc furnace, etc. Various types of products and equipment produced by NPP Vulkan-TM are shown: blowing bottom plugs and assemblies, metering nozzles, gas-dynamic protection of the metal stream from secondary oxidation, two-arm wire-feeding machine mod. TAP 2–1 with unwinding device.Advantages of the equipment for steel casting and extra-furnace steel processing are described.

The basic stages in the development of and the recent developments for metallurgy and foundry by the Vulkan-TM Scientific and Production Enterprise (Tula) are considered. The design features of unified VTseries slide gates of new generation are outlined.

Roll forging for the preliminary profiling of heated material is one of the methods used to optimise material utilisation and minimise the waste of metal as flash in preforming operations as well a...

The article deals with the development of devices for mechanization and automation of metal flow control – steel-pouring ladles sliding gates of the new generation of Vulkan-TM production, the history of their production.The various technical solutions underlying the creation of the sliding gates of the «VT» series, innovative solutions used in design of the sliding gates layouts and their competitive advantages are shown.The design and operation principle of the new development – the device for gas-dynamic protection of the metal stream from secondary oxidation is described.

This article describes the latest advances at the “Vulkan-TM” Scientific-Industrial Association in the production of steel-casting systems and equipment for the secondary treatment of steel. It covers the main stages in the development of the company’s innovative technologies, including a discussion of the advantages and design features of its state-of-the-art slide gates and equipment that protects steel from secondary oxidation. Special attention is given to the direction of its refractories business and the most recent progress in that area.

In the summer of 2010, thermal damages to birch in cultures reached 4.2–4.8 points according to the authors’ five-point scale. In 2011, the stands of birch trees were weakened to variable degrees, but some healthy stands remained. High-density forest massifs and birch forest belts are more drought-resistant. The grass cover is weakly developed therein. Thinned birch cultures become overgrown with herbs and die out after droughts. The root exudates of shrubs depress the intensity of photosynthesis of steppe plants by 10–25%. In vegetation experiments, various species of shrubs stimulate or slow down the growth of shoots and roots and the intensity of photosynthesis of the birch by 10–30%, on average. It is recommended to cultivate birch trees in forest belts using shrubby borders with high allelopathic activity for biological defense of the soil from overgrowth with weedy and steppe plants.

Our long-term surveys have shown improvement in the status of floodplain oak groves in the middle course of the Khoper River after their former mass die-offs. The structure of all forest layers was analyzed, the ontogenetic spectra of the main forest-forming species were studied, and the dynamics of the parcellar structure was revealed. Four levels of wood-pathological and anthropogenic transformation of regional flood-plain oak groves have been established for the first time on the basis of floristic and phytocenotic changes in disturbed forest communities. Diagnostic criteria for their detection have been developed.

This article examines the latest innovations from the NPP “Vulkan-TM” for stopper-less casting and the treatment of steel outside the furnace. It presents the main characteristics and design features of slide gates, equipment for the bottom-blowing of steel with argon, and equipment for making vibroformed refractory products.

New developments for continuous pouring of steel are considered, including slide gates, refractories, promising technologies, etc. A comparative analysis of the designs of domestic and foreign manufacturers is given and the basic operating characteristics and criteria for the selection of refractory slabs for slide gates are presented. The latest developments from NPP Vulkan-TM related to the creation of equipment for continuous casting of steel are considered.

The article presents the results of the development of a mathematical model for calculating the efficiency indices of technological schemes for hot volumetric stamping (GOSH) on crank hot-stamping presses (KGSHP) round in the forgings plan (for gear, pulley and other similar parts). Software solutions obtained on the basis of this model allow choosing from several variants of technological schemes the most effective for using it in production or further improvement.

Contemporary systems are considered for pouring metal from a ladle using unified double-plate slide gates of the BTM series produced by OOO NPP Vulkan-TM and sets of refractories appropriate for them. Attention is drawn to the use of these systems in small metallurgical enterprises. Experience is considered of operating slide refractory plates of domestic and imported production. A method is proposed for manufacturing refractory components for slide gates by casting with subsequent vibration levelling. A device is considered for blowing metal in a ladle with inert gas, improving its quality.

Glycogen storage disease type II (GSDII) is caused by a lack of functional lysosomal acid alpha-glucosidase (GAA). Affected individuals store glycogen in lysosomes beginning during gestation, ultimately resulting in fatal hypertrophic cardiomyopathy and respiratory failure. We have assessed the utility of recombinant adeno-associated virus (rAAV) vectors to restore GAA activity in vivo in a mouse model of GSDII (Gaa(-/-)). A single systemic administration of a rAAV serotype 1 (rAAV1) vector to neonate animals resulted in restored cardiac GAA activity to 6.4 times the normal level (mean=641+/-190% of normal (Gaa(+/+)) levels with concomitant glycogen clearance) at 11 months postinjection. Greater than 20% of normal levels of GAA activity were also observed in the diaphragm and quadriceps muscles. Furthermore, functional correction of the soleus skeletal muscle was also observed compared to age-matched untreated Gaa(-/-) control animals. These results demonstrate that rAAV1 vectors can mediate sustained therapeutic levels of correction of both skeletal and cardiac muscles in a model of fatal cardiomyopathy and muscular dystrophy.

The main ways of reducing expenditure for steel pouring are considered, i.e. import substitution and the optimum frequency of using plates for slide gates. Technical and economic analysis is provided for the use of refractory objects in steel-pouring systems produced by OOO NPP Vulkan-TM.

The achievements of NPP Vulkan-TM in the production of basic forms of production (slide gates, vibration-molded refractories, ceramics, systems for blowing metal with argon, etc.) are analyzed. Specific attention is devoted to the development and introduction of a new slide gate VTM-50V, the results of testing the life of plates of Russian and overseas production within a new generation of slide gates, and also vibration-cast high-alumina refractories within a set of refractories for slide gates of the VTM series.

Conventional methods for rAAV purification that are based on cesium chloride ultracentrifugation have often produced vector preparations of variable quality and resulted in significant loss of particle infectivity. We report here several novel purification strategies that involve the use of non-ionic iodixanol gradients followed by ion exchange or heparin affinity chromatography by either conventional or HPLC columns. These methods result in more than 50% recovery of rAAV from a crude lysate and routinely produce vector that is more than 99% pure. More importantly, the new purification procedures consistently produce rAAV stocks with particle-to-infectivity ratios of less than 100, which is significantly better than conventional methods. The new protocol increases the overall yield of infectious rAAV by at least 10-fold and allows for the complete purification of rAAV in 1 working day. Several of these methods should also be useful for large-scale production.

We have used baculovirus-expressed Rep68 that has been purified to homogeneity to reexamine the binding properties of the Rep protein. We find that Rep68 is capable of binding to a linear DNA sequence that is contained within a 25-bp sequence of the A stem of the adeno-associated virus (AAV) terminal repeat proximal to the B and C palindromes. This has been shown conclusively by demonstrating that Rep68 could specifically bind to a synthetic oligonucleotide containing the 25-bp region in the absence of the other sequences within the terminal repeat. Rep78 was also capable of binding the A stem recognition element, as demonstrated by the fact that a DNA affinity column containing the 25-bp sequence can be used to purify Rep78. The ability to recognize the linear DNA sequence within the A stem provides a mechanism by which the Rep protein can be oriented on the terminal repeat so that only the correct strand is cut at the terminal resolution site (trs site) during terminal resolution. In addition, computer analysis suggests that sequences similar to the A stem element are present within the three AAV promoter regions. Electrophoretic mobility shift experiments clearly demonstrate that the p5 promoter contains a Rep binding sequence. DNase protection experiments indicate that the Rep binding sequence within the p5 promoter is located between the YY1 initiator sequence and the TATA binding site. This position immediately suggests a mechanism by which the Rep protein could act as a repressor or a transactivator of p5 transcription by interacting with either YY1 or TBP. In addition, gel shift experiments suggest that the p19 promoter also contains a Rep binding site. The presence of Rep binding sites upstream of both promoters suggests that these sites may be involved in coordinate regulation of AAV transcription. In addition, we have identified a heterologous Rep binding sequence within pBR322 DNA. A comparison of the sequences within the A stem, p5, and pBR322 binding sites suggests that a repeating GAGC motif is at least part of the Rep recognition sequence. In the accompanying report (D. M. McCarty, J. H. Ryan, S. Zolutukhin, X. Zhou, and N. Muzyczka, J. Virol. 68:4998-5006, 1994), we examine the relative affinity of Rep to the A stem site and the complete terminal repeat. Finally, we also have reexamined the ability of Rep68 and Rep78 to cut at the trs site in substrates that do not contain the B and C palindromes or any apparent secondary structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Recombinant adeno-associated virus type 2 (rAAV) vectors have recently been used to achieve long-term, high level transduction in vivo. Further development of rAAV vectors for clinical use requires significant technological improvements in large-scale vector production. In order to facilitate the production of rAAV vectors, a recombinant herpes simplex virus type I vector (rHSV-1) which does not produce ICP27, has been engineered to express the AAV-2 rep and cap genes. The optimal dose of this vector, d27.1-rc, for AAV production has been determined and results in a yield of 380 expression units (EU) of AAV-GFP produced from 293 cells following transfection with AAV-GFP plasmid DNA. In addition, d27.1-rc was also efficient at producing rAAV from cell lines that have an integrated AAV-GFP provirus. Up to 480 EU/cell of AAV-GFP could be produced from the cell line GFP-92, a proviral, 293 derived cell line. Effective amplification of rAAV vectors introduced into 293 cells by infection was also demonstrated. Passage of rAAV with d27. 1-rc results in up to 200-fold amplification of AAV-GFP with each passage after coinfection of the vectors. Efficient, large-scale production (>109 cells) of AAV-GFP from a proviral cell line was also achieved and these stocks were free of replication-competent AAV. The described rHSV-1 vector provides a novel, simple and flexible way to introduce the AAV-2 rep and cap genes and helper virus functions required to produce high-titer rAAV preparations from any rAAV proviral construct. The efficiency and potential for scalable delivery of d27.1-rc to producer cell cultures should facilitate the production of sufficient quantities of rAAV vectors for clinical application.

1. Minimum local head losses in an intake are observed with a horizontal arrangement of the intake opening sill (ϕsill=0°). In the case of small intake opening heights (t/ dw≤0.25) the ceiling and conical roller gate bottom of these intakes should be inclined at angle ϕceil=22–30° to the horizontal to reduce the head losses. 2. For relative heights of the intake openings t/dw≥0.3 the intakes withϕsill≤25° and conical roller gate bottom have the same head losses. 3. To reduce the head losses in an intake withϕsill>25° (when t/dw

With a single intravenous administration to albino rats of both sexes of nospanum and halidor in a dose of 2 mg/kg and dibazol--in 1 mg/kg produce activation of fibrinolysis, while euphylline in a dose of 12 mg/kg has no effect on this process. A protracted introduction by the subcuataneous route of halidor and nospanum in a dose of 10 mg/kg, of dibazol--in 5 mg/kg and of euphylline intramuscularly in a dose of 24 mg/kg depresses in animals the activity of the proteolytic process. It was found that in vitro nospanum, halidor and dibazol accelerate fibrinolysis, whereas the presence of euphylline in the blood plasma deccelerates this process.

An investigation of the thrombocytes adhesion after Hellem (1960) showed that "in vitro" tests norepinephrine, epinephrine, histamine, serotonin and adenosine-diphosphate, when used in doses of 100-25,0 gamma/ml, were capable of raising the thrombocytes adhesion, while heparin administered in doses of 0.5-0.05 U/ml depressed and in a dose of 0.025 U/ml mildly activated this capacity of the thrombocytes. In the presence of heparin the ability of biogenic amines to induce the adhesion of thrombocytes decreased. Between concentration of the agents and the adhesive index of thrombocytes there exists a two-way logarithmic relationship. Intravenous administration of serotonin in a dose of 5 mg/kg and of epinephrine in an amount of 0.05 mg/kg to rabbits increased the adhesivity of thrombocytes, whereas intravenous introduction of 100 un/kg of heparin tended to greatly reduce it. On introduction of serotonin and epinephrine to rabbits against the background of heparin their ability to activate the thrombocytes adhesion diminished quite significantly. The logarithm of time lapsed from the instance of the heparin administration is linearly dependent on the logarithms of values characterizing the adhesivity of thrombocytes. Intravenous administration of norepinephrine and histamine in a dose of 0.5 mg/kg did not cause any changes in the adhesive properties of thrombocytes.

Nonachlazine at concentrations 10(-6)--10(-4)M inhibited platelet aggregation in rabbits induced by adrenalin in vitro. The same concentrations of the drug produced an appreciable increase in aggregation reversibility. Intravenous injection of nonachlazine into the rabbit 50 minutes prior to adrenalin protected the platelets against the aggregation activity of adrenalin but did not affect deaggregation.

Nonachlazin binds in vitro heparin in blood plasma and aqueous medium. This interaction complies with logarithmic dependence. Isoptin increases in vitro plasma susceptibility to heparin, reduces the period of whole blood coagulation and thrombin time. Riboxin does not produce in vitro any effect on the blood coagulation parameters and heparin susceptibility. Single and chronic adminstration of the drugs exerts no effect on blood coagulation. Prolonged use of riboxin promotes the increased level of endogenous heparin. Both single and chronic administration of the drugs potentiates the anticoagulant action of heparin.