Delivery of Experimental mRNA Vaccine Encoding the RBD of SARS-CoV-2 by Jet Injection.

We studied a needle-free jet injection delivery of an experimental mRNA vaccine encoding the receptor-binding domain of the SARS-CoV-2 S protein (mRNA-RBD). Immunization of BALB/c mice with mRNA-RBD by a needle-free jet injector induced high levels of antibodies with virus-neutralizing activity and a virus-specific T-cell response. The immune response was low in the group of mice that received intramuscular injection of mRNA-RBD. The effectiveness of this simple and safe method of mRNA delivering has been demonstrated. Thus, jet injection of mRNA vaccine can be a good alternative to lipid nanoparticles.

DNA Vaccine Encoding the Artificial T-Cell Polyepitope Immunogen of Tick-Borne Encephalitis Virus.

A promising approach to the development of new means for preventing infection caused by tick-borne encephalitis virus can be DNA vaccines encoding polyepitope T-cell immunogens. A DNA vaccine pVAX-AG4-ub encoding an artificial polyepitope immunogen that includes cytotoxic and T-helper epitopes from the NS1, NS3, NS5, and E proteins of the tick-borne encephalitis virus has been obtained. The developed construct ensured the synthesis of the corresponding mRNAs in transfected eukaryotic cells. Immunization of mice with pVAX-AG4-ub induced the formation of a virus-specific T-cell response providing 50% protection from lethal infection with the virus.

Combustion of sewage sludge in a fluidized bed of catalyst: ASPEN PLUS model.

This paper presents the results of the simulation of a sewage sludge combustion plant with a productivity of 6 tons per hour using the ASPEN Plus. It is shown that catalytic combustion technology can be used for the efficient utilization of mechanically dehydrated sludge with the moisture of ~75% in autothermal mode (without the use of additional fuel). At the same time, the plant for utilization of 6.0 tons of sludge per hour enables us to obtain 3.07 MW of heat energy. It is shown that the sludge moisture and its calorific value significantly affect the combustion process. Thus, at the moisture of less than 72%, additional water supply is necessary to avoid overheating of the catalyst bed. In the case of an increase in sludge moisture of more than 76%, an additional supply of fuel (for example, brown coal) is required. Also, the article discusses the emissions of harmful substances generated during sewage sludge combustion and methods for their utilization.

Recent advances in one-stage conversion of lipid-based biomass-derived oils into fuel components - aromatics and isomerized alkanes.

Nowadays, production of biofuels is a rather hot topic due to depleting of conventional fossil fuel feedstocks and a number of other factors. Plant lipid-based feedstocks are very important for production of diesel-, kerosene-, and gasoline-like hydrocarbons. Usually, (hydro)deoxygenation processes are aimed at obtaining of linear hydrocarbons known to have poor fuel characteristics compared to the branched ones. Thus, further hydroisomerization is required to improve their properties as motor fuel components. This review article is focused on conversion of lipid-based feedstocks and model compounds into high-quality fuel components for a single step - direct cracking into aromatics and merged hydrodeoxygenation-hydroisomerization to obtain isoparaffins. The second process is quite novel and a number of the research articles presented in the literature is relatively low. As auxiliary subsections, hydroisomerization of straight hydrocarbons and techno-economic analysis of renewable diesel-like fuel production are briefly reviewed as well.

[Optimization of the invasive strategy for acute coronary syndrome in patients of the older age group.]

A study is presented on the effectiveness and safety of various anticoagulants used in patients of an older age group with acute coronary syndrome during percutaneous coronary interventions. Bivalirudin was shown to be highly effective in comparison with unfractionated heparin and monafram in relation to the amount of bleeding that occurs in the postoperative period and adverse cardiovascular complications.

Geographic variation of life-history traits in the sand lizard, Lacerta agilis: testing Darwin's fecundity-advantage hypothesis.

The fecundity-advantage hypothesis (FAH) explains larger female size relative to male size as a correlated response to fecundity selection. We explored FAH by investigating geographic variation in female reproductive output and its relation to sexual size dimorphism (SSD) in Lacerta agilis, an oviparous lizard occupying a major part of temperate Eurasia. We analysed how sex-specific body size and SSD are associated with two putative indicators of fecundity selection intensity (clutch size and the slope of the clutch size-female size relationship) and with two climatic variables throughout the species range and across two widespread evolutionary lineages. Variation within the lineages provides no support for FAH. In contrast, the divergence between the lineages is in line with FAH: the lineage with consistently female-biased SSD (L. a. agilis) exhibits higher clutch size and steeper fecundity slope than the lineage with an inconsistent and variable SSD (L. a. exigua). L. a. agilis shows lower offspring size (egg mass, hatchling mass) and higher clutch mass relative to female mass than L. a. exigua, that is both possible ways to enhance offspring number are exerted. As the SSD difference is due to male size (smaller males in L. a. agilis), fecundity selection favouring larger females, together with viability selection for smaller size in both sexes, would explain the female-biased SSD and reproductive characteristics of L. a. agilis. The pattern of intraspecific life-history divergence in L. agilis is strikingly similar to that between oviparous and viviparous populations of a related species Zootoca vivipara. Evolutionary implications of this parallelism are discussed.

Surface phonon polariton characteristics of In(0.04)Al(0.06)Ga(0.90)N/AlN/Al(2)O(3) heterostructure.

Surface phonon polariton (SPP) characteristics of In(0.04)Al(0.06)Ga(0.90)N/AlN/Al(2)O(3) heterostructure are investigated by means of p-polarized infrared (IR) attenuated total reflection spectroscopy. Two absorption dips corresponding to In(0.04)Al(0.06)Ga(0.90)N SPP modes are observed. In addition, two prominent dips and one relatively weak and broad dip corresponding to the Al(2)O(3) SPP mode, In(0.04)Al(0.06)Ga(0.90)N/Al(2)O(3) interface mode, and Al(2)O(3) bulk polariton mode, respectively, are clearly seen. No surface mode feature originating from the AlN layer is observed because it is too thin. Overall, the observations are in good agreement with the theoretical predictions.

Modulated angle beam ultrasonic spectroscopy for evaluation of imperfect interfaces and adhesive bonds.

An experimental method incorporating high frequency pulsed angle beam ultrasonic measurements modulated by low frequency vibrations of a bonded structure is described. This method uses parametric/nonlinear mixing between high and low frequencies to characterize adhesive degradation. It is demonstrated that good quality (undamaged) bonds exhibit little dependence of ultrasonic signature on the overlay of low frequency vibration loads; however, environmentally degraded or imperfect bonds exhibit strong modulation of the resonance frequency of the ultrasonic signal reflected from the bond. The results are interpreted using a model for normal and oblique wave interaction with two nonlinear interfaces separated by an adhesive layer under quasi-static stress modulation.

Infrared-phonon-polariton resonance of the nonlinear susceptibility in GaAs.

Nonlinear probing of the fundamental lattice vibration of polar crystals is shown to reveal insight into higher-order cohesive lattice forces. With a free-electron laser tunable in the far infrared we experimentally investigate the dispersion of the second-order susceptibility due to the phonon resonance in GaAs. We observe a strong resonance enhancement of second harmonic light generation at half the optical phonon frequency, and in addition a minimum at a higher frequency below the phonon frequency. Measuring this frequency and comparison to a theoretical model allows the determination of competing higher-order lattice forces.

Aldosterone content in plasma, erythrocytes and skeletal muscles in Icenko-Cushing's syndrome.

Aldosterone concentration was measured in plasma, erythrocytes and skeletal muscles in 34 patients with Icenko-Cushing's syndrome (ICS). It was established that aldosterone levels in the erythrocytes and whole blood of these patients were elevated, while aldosterone content in the plasma and muscular tissue of the patients was normal. Only in a small group of patients (N = 4) aldosterone levels positively correlated with arterial pressure (BP) and central hemodynamic parameters. Following 10 minutes of headdown tilt (-15 degrees), erythrocyte aldosterone level in the group of healthy controls (N = 12) was markedly elevated, but not in the group of patients with ICS. The results of the study suggest that erythrocytes can be viewed as a mobile aldosterone "depot" and may operate to mediate depressor effects of certain hormones on central hemodynamics.

[Interrelation between hemodynamic parameters and the functional state of components of the endocrine system in patients with pheochromocytoma]. / Vzaimosviaz' pokazatelei gemodinamiki i funktsional'nogo sostoianiia nekotorykh zven'ev éndokrinnoi sistemy u bol'nykh feokhromotsitomoi.

Ten patients with pheochromocytoma were examined before operation, 8 were examined 2-4 weeks after surgical treatment, and 30 in the long-term periods after elimination of hypercatecholaminemia. The patients with pheochromocytoma manifested activation of the renin-aldosterone system and inhibition of PGE2 secretion. In the long-term postoperative period, the level of aldosterone in the blood plasma was increased and that of PGE2 was reduced. In the patients with pheochromocytoma, the interrelation was discovered between the magnitude of arterial blood pressure and secretion of catecholamines, deoxycorticosterone, depressor prostaglandins. At different times after surgical treatment the central hemodynamics was found to be related to the level of mineralocorticoid hormones.

Study of the mechanism of action of adenosylcobalamindependent glycerol dehydratase from Aerobacter aerogenes. II. The inactivation kinetics of glycerol dehydratase complexes with adenosylobalamin and its analogs.

The inactivation kinetics of vacterial glycerol dehydratase (EC 4.2.1.30) in the course of its reaction with adenosylcobalamin (AdoCbl) and its analogs were investigated. It was shown that the inactivation rate of apoenzyme complexes with AdoCbl analogs is determined by the nature of the analogs employed and probably by the rate of their conversion into hydroxycobalamins. A possible inactivation mechanism of glycerol dehydratase is discussed.

Study on the mechanism of action of adenosylcobalamin-dependent glycerol dehydratase from Aerobacter aerogenes. I. Role of structural components of adenosylcobalamin the formation of the active site of glycerol dehydratase.

A new method of partial chemical synthesis of adenosylcobalamin (Co alpha-[alpha-5,6-diemethylbenzimidazolyl)]-Co beta-adenosylcobamide, AdoCbl) analogs has been developed. A series of derivatives of AdoCbl modified in the nucleoside and nucleotide ligands and corrin macrocycle have been obtained. The interaction of AdoCl analogs with glycerol dehydratase (EC 4.2.1.30) from Aerobacter aerogenes has been investigated. It has been shown that the nucleoside ligand of AdoCbl provides no essential contribution to the binding of apoenzyme but the preservation of the exact structure of the 1-N and 2-C positions of adenine appears essential for the catalysis. The coordination bond between the Co and nucleotide ligand of AdoCl does not play a decisive role in glycerol dehydratase activity. To form the active site of the glycerol dehydrates, the nucleotide in the AdoCbl structure is essential since nucleotide elimination results in a 100-fold increase of Ki for the corresponding analog. In the binding of AdoCbl with apoenzyme, the main role belongs to the corrin macrocycle, in which the e-propionamide group is significant for binding with apoenzyme, but presumably not essential for catalysis.

Self-association of human erythrocyte phosphofructokinase. Kinetic behaviour in dependence on enzyme concentration and mode of association.

The kinetic behaviour of human erythrocyte phosphofructokinase has been analyzed over a relative wide range of enzyme concentration (0.01 -- 1.7 mug/ml). The kinetic cooperativity which becomes apparent when the enzymic reaction rate is plotted versus the fructose 6-phosphate concentration decreases with increasing enzyme concentration. Simultaneously, a decrease of the half-saturation concentration for fructose 6-phosphate [S]0.5 is observed. Maximum velocity passes through a maximum at increasing enzyme concentrations. Sets of curves representing specific enzymic activity of phosphofructokinase versus enzyme concentration obtained at various fixed concentrations of fructose 6-phosphate and ATP are analyzed. The shapes of these curves are interpreted in terms of an association model of human erythrocyte phosphofructokinase, in which an inactive dimer (Mr 190000) and active multimers of the dimeric form are involved. The conclusion is drawn that the sigmoidal shape of the plots of the enzymic reaction rate versus fructose 6-phosphate concentration is partially caused by a displacement of the equilibrium between different states of association of phosphofructokinase to multimers by this substrate. On the other hand, the inhibition of the enzyme by high concentrations of ATP may be partially caused by a shift of this equilibrium to the state of the inactive dimer.

[Role of monovalent cations in reactions catalyzed by glycerol dehydrase from Aerobacter aerogenes].

Cobamide-dependent glyceroldehydrase (GDH) is shown to have an absolute requirement in monovalent cations: K+, NH4+, Tl+, Rb+ and Cs+. Dependencies of initial dehydratation rates of three substrates: glycerol, ethyleneglycol and 1,2-propandiol on the concentration of K+ are studied. Km values for K+, NH4+ and Tl+ are calculated to be 7-10-3, 4-10-3 and 1-10-3 M respectively. Effect of K+ on Km values for glycerol and coenzyme and on maximal reaction rate is investigated. It is shown that the apparent affinity of the substrate to the enzyme does not depend on monovalent cation; the apparent affinity of the coenzyme somewhat changes with the change of K+ concentration. Maximal reaction rate increases with the increase of K+ content. On the basis of kinetic data obtained possible mechanism of the activating effect of monovalent cations in reactions, catalyzed by GDH, is discussed.

[Kinetic manifestations of slow isomerization of allosteric enzyme for the model of Monod, Wyman and Changeux].

A shape of the curves of a product accumulation in time (t) is analysed for the variant of Monod, Wyman and Changeux model which is characterized by comparable rates of equilibration between R and T enzyme forms on the one hand and the enzymatic process on the other hand. It is assumed that the complex of R and T forms with substrate are in rapid equilibrium with the free components. The character of the dependences of effective constant of R denoting T isomerization and the value of tau on substrate concentration are analysed (tau is the intercept of t-axis for linear asymptota of the curve of product concentration versus time at t leads to infinity). It is also shown that the low rate of R denoting T isomerization may be manifested by the shape of the plot of initial reaction rate versus substrate concentration unusual for the model of Monod et al. (the plots with intermediate plateau and ones with Hill's coefficient of cooperativity less than unity).