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Abstract: The results of studying the bone tissue samples of humans and domestic pigs from some ancient monuments of the Kerch Peninsula in Crimea are given. The diets of humans and animals are determined by the content of carbon and nitrogen isotopes in their bones at the time of death. The study is conducted using a DELTA V mass spectrometer, an elemental analyzer, and devices for their connection. It is revealed that the inhabitants of ancient settlements barely ate any sea fish. It was used as a food for pigs only occasionally.

Nuclear power plants in France and Germany operate in a loadfollowing mode to help stabilise the electricity grid on a minuteby-minute basis, and to balance daily and weekly shifts in [...]

Comprehensive research of ore-bearing differentiated intrusions of the Keulik–Kenirim structural unit, which represents a fragment of the Paleoproterozoic Pechenga–Varzuga Belt, has been carried out for the first time. The intrusions are subvolcanic by type and lenticular in shape, nearly conformable and steeply dipping. They are made up of peridotite, olivine and plagioclase pyroxenites, and gabbro metamorphosed under amphibolite facies conditions along with host basic volcanics. All intrusive rocks are enriched in TiO2 and FeO. Sulfide Cu–Ni mineralization is represented by disseminated, pocket, and stringer-disseminated types, which are clustered in the peridotitic zone as hanging units and bottom lodes. The Ni content in disseminated ore is estimated at 0.45–0.55 wt % and 1.15–3.32 wt % in ore pockets; the Cu grades are 0.17–0.20 and 0.46–5.65 wt %, respectively. To determine the age of intrusions and metamorphism of intrusive and volcanic rocks, various isotopic systems have been used: Sm–Nd (TIMS) in rock and U–Pb (SIMS SHRIMP) and Lu–Hf (LA-ICP-MS) in zircon. Conclusions on the origin of zircons are based on concentrations of trace elements including REE therein and Hf–Nd correlation in zircons and rocks. The U–Pb system of zircons reflects episodes of igneous rock formation (1982 ± 12 Ma) and their postmagmatic transformation (1938 ± 20 Ma). The last disturbance of the U–Pb isotopic system occurred 700 and 425 Ma. Xenogenic zircons dated from 3.17 to 2.65 Ga have been revealed in the studied samples. These zircons were captured by magma from the Archean basement during its ascent. The intrusions were emplaced synchronously with economic ore formation in the Pechenga ore field (1985 ± 10 Ma). The peak metamorphism of intrusive rocks under amphibolite facies conditions is recorded at 40 Ma later. The differentiated intrusions of the Keulik–Kenirim structural unit are close in their internal structure, mineralogy, and geochemistry, as well as in age and features of related Cu–Ni mineralization to ore-bearing intrusions of the Pechenga ore field, which are derivatives of ferropicritic (ferriferous) magmatism.

Abstract We have conducted experimental and clinical approbation of two preparations coded RL-175 and RL-S from the new generation of synthesized active substances. Their action is directed to increase the [...]

Abstract We have conducted experimental and clinical approbation of two preparations coded RL-175 and RL-S from the new generation of synthesized active substances. Their action is directed to increase the [...]

The ability to accurately and efficiently compute quantum-mechanical partial atomistic charges has many practical applications, such as calculations of IR spectra, analysis of chemical bonding, and classical force field parametrization. Machine learning (ML) techniques provide a possible avenue for the efficient prediction of atomic partial charges. Modern ML advances in the prediction of molecular energies [i.e., the hierarchical interacting particle neural network (HIP-NN)] has provided the necessary model framework and architecture to predict transferable, extensible, and conformationally dynamic atomic partial charges based on reference density functional theory (DFT) simulations. Utilizing HIP-NN, we show that ML charge prediction can be highly accurate over a wide range of molecules (both small and large) across a variety of charge partitioning schemes such as the Hirshfeld, CM5, MSK, and NBO methods. To demonstrate transferability and size extensibility, we compare ML results with reference DFT calculations on the COMP6 benchmark, achieving errors of 0.004e–(elementary charge). This is remarkable since this benchmark contains two proteins that are multiple times larger than the largest molecules in the training set. An application of our atomic charge predictions on nonequilibrium geometries is the generation of IR spectra for organic molecules from dynamical trajectories on a variety of organic molecules, which show good agreement with calculated IR spectra with reference method. Critically, HIP-NN charge predictions are many orders of magnitude faster than direct DFT calculations. These combined results provide further evidence that ML (specifically HIP-NN) provides a pathway to greatly increase the range of feasible simulations while retaining quantum-level accuracy.

This paper presents the results of a complex study (morphology of grains, internal texture in cathodoluminescence and backscattered electrons, microprobe analysis, Lu–Hf data) of five groups (generations) of zircon crystals differing in age and separated from the same granulite sample pertaining to the Bug River Complex of the Ukrainian Shield. The data show that the oldest zircon crystals of the first group (3.74 Ga in age) are xenogenic and initially crystallized from a granitic melt; zircon of the second group (3.66 Ga) formed from a mafic melt contaminated by felsic country rocks. The third group (3.59 Ga) is represented by zircons that formed about 100 Ma later than the second group under conditions of granulite-facies metamorphism and with the participation of fluid-saturated anatectic melt. Two Paleoproterozoic zircon groups (~2.5 and 2.1 Ga) also formed under granulite-facies conditions; to a certain extent, their structure and composition were controlled by fluid. The geochemistry of all zircon generations provides evidence for their crystallization in the continental crust, but from the sources differing in the contribution of mantle-derived material and in oxygen fugacity.

Les petits réacteurs modulaires (Small modular reactor- SMR) d'une puissance inférieure à 300 MWe s'appuient sur une fabrication en série des modules de réacteurs. Ils pourraient élargir le champ de développement de l'énergie nucléaire, dans des zones déjà connectées au réseau électrique et dans des régions isolées. L'AEN estime que, dans les scénarios les plus favorables, 21 GWe de SMR peuvent être déployés d'ici 2035, essentiellement dans des économies émergentes. Mais le développement des marchés pour les SMR dépendra avant tout du succès des premiers prototypes.

ABSTRACTBacillus anthracisis a tier 1 select agent with the potential to quickly cause severe disease. Rapid identification of this pathogen may accelerate treatment and reduce mortality in the event of a bioterrorism attack. We developed a rapid and sensitive assay to detect B. anthracisbacteremia using a system that is suitable for point-of-care testing. A filter-based cartridge that included both sample processing and PCR amplification functions was loaded with all reagents needed for sample processing and multiplex nested PCR. The assay limit of detection (LOD) and dynamic range were determined by spiking B. anthracisDNA into individual PCR mixtures and B. anthracisCFU into human blood. One-milliliter blood samples were added to the filter-based detection cartridge and tested for B. anthracison a GeneXpert instrument. Assay specificity was determined by testing blood spiked with non-anthrax bacterial isolates or by testing blood samples drawn from patients with concurrent non-B. anthracisbacteremia or nonbacteremic controls. The assay LODs were 5 genome equivalents per reaction and 10 CFU/ml blood for both the B. anthracisSterne and V1B strains. There was a 6-log10dynamic range. Assay specificity was 100% for tests of non-B. anthracisbacterial isolates and patient blood samples. Assay time was less than 90 min. This automated system suitable for point-of-care detection rapidly identifies B. anthracisdirectly from blood with high sensitivity. This assay might lead to early detection and more rapid therapy in the event of a bioterrorism attack.

Background: Development of a universal cancer vaccine for the prevention of all cancers has been under development for many years. Antiangiogenic cancer vaccines elicit immune responses with the potential of destroying tumor vasculature endothelial cells without affecting vasculature integrity in normal tissues. The methods used in the development of antigen compositions comprising these vaccines have been recently improved and described in this report in the context of SANTAVAC ™ development - the first cancer vaccine based on endothelial cell heterogeneity. Methods: The present report summarizes data related to SANTAVAC™ development, including technical key points associated with optimal SANTAVAC™ production, a description of the composition required for preparing cancer vaccines with the highest predicted efficacy and safety, and a strategy for SANTAVAC™ large-scale implementation. Patents related to SANTAVAC™ and other universal cancer vaccines are also described. Results: SANTAVAC ™ was shown to be the most promising antigen composition for anti-cancer vaccination, allowing for immune targeting of the tumor vasculature in experimental models with a high predicted efficacy (up to 60), where efficacy represents the fold decrease in the number of endothelial cells with a tumor-induced phenotype and directly related to predicted arrest of tumor growth. Conclusion: The use of SANTAVAC ™ as a universal antigenic composition may spur vaccine development activities resulting in a set of therapeutic or prophylactic vaccines against different types of solid cancers.

Multidisciplinary studies of zircons, rock-forming minerals and the whole-rock composition of granulite samples from the Bug Granulite–Gneiss Complex, Ukraine (including ion microprobe REE analysis, secondary ion mass spectrometry (SIMS) U–Pb and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) Lu–Hf analysis of zircons from a single sample) have revealed three major stages in the geological evolution of the complex. (i) At 3.66 Ga, a mafic intrusion contaminated with felsic rocks formed, as evidenced by 3.74 Ga zircon xenocrysts with inclusions of plagioclase, K-feldspar and quartz. (ii) At 3.59–3.55 Ga, high-temperature and high- to moderate-pressure granulite-facies metamorphism accompanied by migmatization and deformation resulted in the formation of mafic granulites. (iii) At 2.1–2.0 Ga, metamorphic overprinting occurred, and metatrachybasaltic dykes intruded at approximately 2.0 Ga. The metamorphic mineral assemblages recorded in the dykes formed at temperatures similar to those of the 3.59–3.55 Ga metamorphism but at pressures 2–3 kbar lower. This metamorphism disturbed the Sm–Nd whole-rock system, altered the Hf isotope system of the older zircons and resulted in Pb loss in small zircon grains. This complex event history recorded in zircons from a single rock corresponds to major stages of the geological evolution of both the Dniester–Bug Province and the entire Ukrainian Shield.

ABSTRACTExtensively drug-resistant (XDR) tuberculosis (TB) cannot be easily or quickly diagnosed. We developed a rapid, automated assay for the detection of XDR-TB plus resistance to the drug isoniazid (INH) for point-of-care use. Using a simple filter-based cartridge with an integrated sample processing function, the assay identified a wide selection of wild-type and mutant sequences associated with XDR-TB directly from sputum. Four new large-Stokes-shift fluorophores were developed. When these four Stokes-shift fluorophores were combined with six conventional fluorophores, 10-color probe detection in a single PCR tube was enabled. A new three-phase, double-nested PCR approach allowed robust melting temperature analysis with enhanced limits of detection (LODs). Finally, newly designed sloppy molecular beacons identified many different mutations using a small number of probes. The assay correctly distinguished wild-type sequences from 32 commonly occurring mutant sequences tested in gyrA, gyrB, katG, and rrsgenes and the promoters of inhAand eisgenes responsible for resistance to INH, the fluoroquinolone (FQ) drugs, amikacin (AMK), and kanamycin (KAN). The LOD was 300 CFU of Mycobacterium tuberculosisin 1 ml sputum. The rate of detection of heteroresistance by the assay was equivalent to that by Sanger sequencing. In a blind study of 24 clinical sputum samples, resistance mutations were detected in all targets with 100% sensitivity, with the specificity being 93.7 to 100%. Compared to the results of phenotypic susceptibility testing, the sensitivity of the assay was 75% for FQs and 100% each for INH, AMK, and KAN and the specificity was 100% for INH and FQ and 94% for AMK and KAN. Our approach could enable testing for XDR-TB in point-of-care settings, potentially identifying highly drug-resistant TB more quickly and simply than currently available methods.

According to the OECD/NEA estimates, nuclear power plants (NPPs), whether with a large reactor or with small modular reactors (SMRs), are competitive with many other electricity generation technologies in a significant number of cases, one of the exceptions being natural gas in the USA with the current level of prices. However, SMRs have particular features and requirements setting conditions for their deployment. This paper presents the preliminary analysis by OECD/NEA of the economics, opportunities, and market for small nuclear reactors.

Among the potential cancer immunotherapies, vaccination against antigens expressed by endothelial cells lining the tumor vasculature represents one of the most attractive options because this approach may prevent the growth of any solid tumor. Therefore, endothelial cells can be used as a source of antigens for developing a so-called “universal” cancer vaccine. Unfortunately, efficient endothelial cell-based cancer vaccines have not yet been developed because previous approaches utilized direct endothelial cell immunizations which is not effective and can result in the elicitation of autoimmune responses associated with systemic autoimmune vasculitis. Recently, the heterogeneity of the endothelial cell surface was defined using an in vitro system as a means of developing antiangiogenic cancer vaccines. This analysis demonstrated that tumors induced specific changes to the microvascular of human endothelial cell (HMEC) surface thereby providing a basis for the design of endothelial cell-based vaccines that directly target the tumor endothelium.1This commentary further describes HMEC heterogeneity from the perspective of designing an endothelial cell-based universal (for the treatment of all solid tumors) cancer vaccine with high immunogenicity that does not pose the risk of eliciting autoimmunity.

Immune-mediated damage to tumor vessels is a potential means of preventing solid tumor progression. Antiangiogenic cancer vaccines capable of inducing this kind of damage include formulations comprised of endothelial cell-specific antigens. Identification of antigens capable of eliciting efficient vaccination is difficult because the endothelial cell phenotype is affected by surrounding tissues, including angiogenic stimuli received from surrounding tumor cells. Therefore, phenotype endothelial cell variations (heterogeneity) were examined in the context of the development of an efficient vaccine using mass spectrometry-based cell surface profiling. This approach was applied to primary human microvascular endothelial cell (HMEC) cultures proliferated under growth stimuli provided by either normal tissues (growth supplement from human hypothalamus) or cancer cells (MCF-7, LNCap and HepG2). It was found that tumors induced pronounced, tumor type-dependent changes to HMEC surface targets that in an in vitro model of human antiangiogenic vaccination directly facilitated HMEC escape from cytotoxic T cell-mediated cell death. Furthermore, it was found that tumors influenced the HMEC phenotype unidirectionally and that HMEC imunogenicity was reciprocal to the intensity of tumor-induced changes to the HMEC surface. These findings provide data for the design of tumor-specific endothelial cell based vaccines with sufficient immunogenicity without posing a risk to the elicitation of autoimmunity if administered in vivo.

The article evaluates the status of small nuclear reactors of less than about 300 megawatt electrical (MWe) and provides an initial check of their economic competitiveness. It mentions a growing interest in such reactors due to a number of reasons which include the potential for reduced costs, the appropriateness of use in smaller grids and the possibility of modular construction. A table of design status of advanced, small modular reactors (SMRs) and figures is also presented.

The geological structure, age, and genesis of sedimentary—volcanogenic, metamorphic, and metasomatic rocks from the Terskii greenstone belt fringing the southern Imandra—Varzuga structure in the southeastern Kola Peninsula are discussed with defining main stages in endogenic activity of the region in the Late Archean and Early Proterozoic. The U-Pb method (SHRIMP-II, ID-TIMS, and Pb-LS techniques) was used to determine the age of volcano-sedimentary rocks of the Imandra Group as well as that of magmatic and superimposed metamorphic and metasomatic processes. The basic—intermediate metavolcanics of the Imandra Group are dated at 2.67 Ga, which corresponds to the Lopingian Gimol’skii Superhorizon (Late Archean). The Archean metavolcanics were subjected to Early Proterozoic regional metamorphism 2.1 Ga ago and metasomatic processes in the period of 1.85 to 1.77 Ga ago. The obtained data indicate multistage evolution of rock formation in the Terskii greenstone belt located in the southern flank of the Imandra—Varzuga structure in the Kola Peninsula.

Abstract: This study presents the first U/Pb SHRIMP II dates on zircons from metasomatic sillimanitehypersthene rocks within the Porya Guba nappe of the Lapland Granulite Belt. The results yielded a Paleoproterozoic Svecofennian age (1913–1914 Ma) of the HT/HP metasomatism in shear zones during collision-related metamorphic events in the Lapland Granulite Belt.

Primers that contain portions noncomplementary to the target region are usually used to add to the PCR product a utility sequence such as a restriction site or a universal probe binding site. We have demonstrated that primers with short 5′ AT-rich overhangs increase real-time PCR fluorescent signal. The improvement is particularly significant for difficult to amplify templates, such as highly variable viral sequences or bisulfite-treated DNA.

Stabilizing modified bases incorporated in primers allows the reduction of housekeeping gene primer concentration not possible with regular primers without sacrificing amplification efficiency. Low primer concentration allows coamplification of the most abundant housekeeping genes with very rare templates without mutual inhibition. Real-time polymerase chain reaction (PCR) coamplification of 18S ribosomal RNA with several genes of interest was used in this study with MGB Eclipse® (Nanogen, San Diego, CA) hybridization probes. The results may be useful for high throughput gene expression studies as they simplify validation experiments.

It has been recently shown that insulin retains its biological activity after receptor-directed internalization and it may affect the cell metabolism by interaction with cytosolic insulin-binding proteins (CIBPs). Using affinity chromatography combined with SDS-PAGE and MALDI-TOF mass-spectrometry we have identified 7 proteins from mouse liver cells that specifically bind to the insulin, including adenylate kinase 2 (25.6 kD), kinesin superfamily protein 20B (26.0 kD), hepatic arginase 1 (34.8 kD), fructosebisphosphate aldolase B (39.5 kD), 4-hydroxyphenylpyruvate dioxygenase (45.1 kD), betainehomocysteine methyl-transferase (45.0 kD) and KRIT1 (83.4 kD).

The differential and integral light scattering by dielectric surfaces is studied theoretically taking a thin near-surface defect layer into account. The expressions for the intensities of differential and total integral scattering are found by the Green function method. Conditions are found under which scattering by the defect layer can be neglected compared to scattering by the surface roughness. A method is proposed to separate the scattering from the surface roughness and the defect layer. Estimates are made of the typical changes in the permittivity and scattering intensity which correspond to the defect layer related to the higher concentration of structural defects in the near-surface region.

AbstractA new strategy based on the use of cooperative tandems of short oligonu-cleotide derivatives (TSOD) has been proposed to discriminate a “right” DNA target from a target containing a single nucleotide discrepancy. Modification of a DNA target by oligodeoxyribonucleotide reagents was used to characterize their interaction in the perfect and mismatched complexes. It is possible to detect any nucleotide changes in the binding sites of the target with the short oligonucleotide reagent. In the presence of flanking di-3′,5′-N-(2-hydroxyethyl)phenazinium derivatives of short oligonucleotides (effectors) the tetranucleotide alkylating reagent modifies DNA target efficiently and site-specifically only in the perfect complex and practically does not modify it in the mismatched complex. It has been shown that TSOD is much more sensitive tool for the detection of a point mutation in DNA as compared to a longer oligonucleotides.

A nitrogen cryosprayer and a liquid-nitrogen-cooled cryodestructor are described. They are general-purpose experimental devices designed for fast cooling (freezing) of biological objects, in particular, tissues of living organisms.

A theoretical study was made of the differential and integral scattering of light by high-precision optical dielectric surfaces. The technique of modified curvilinear transformation was employed to derive the expressions that correspond to the effect of irregularity slope fluctuations, which is not considered in the conventional vector theory of differential scattering. It is shown that it is possible to neglect the effect of irregularity slope to a high degree of accuracy and thereby resort to conventional vector theory to determine the roughness parameters. Expressions were derived for the total integral scattering for different ratios between the correlation length and the wavelength of the scattered radiation.

DNA probes with conjugated minor groove binder (MGB) groups form extremely stable duplexes with single-stranded DNA targets, allowing shorter probes to be used for hybridization based assays. In this paper, sequence specificity of 3'-MGB probes was explored. In comparison with unmodified DNA, MGB probes had higher melting temperature (T(m)) and increased specificity, especially when a mismatch was in the MGB region of the duplex. To exploit these properties, fluorogenic MGB probes were prepared and investigated in the 5'-nuclease PCR assay (real-time PCR assay, TaqMan assay). A 12mer MGB probe had the same T(m)(65 degrees C) as a no-MGB 27mer probe. The fluorogenic MGB probes were more specific for single base mismatches and fluorescence quenching was more efficient, giving increased sensitivity. A/T rich duplexes were stabilized more than G/C rich duplexes, thereby leveling probe T(m)and simplifying design. In summary, MGB probes were more sequence specific than standard DNA probes, especially for single base mismatches at elevated hybridization temperatures.

A volumetric model of accidental oil spills on the land surface was developed, based on numerical methods for solving hydrodynamic equations, and taking into account the processes of oil spreading over the surface, its filtration into the soil and evaporation into the atmosphere. Based on the results of calculations using the hydrodynamic model for the most probable scenarios of oil spills, it is possible to obtain an estimate of the spatial-temporal scale of the spill, which, together with data on the terrain and the presence of water bodies, is the input data for the expert model. Based on the joint use of the hydrodynamic model of the oil spill and expert technologies, the territory of the Nenets Autonomous Okrug and the South Khylchuyu-Varandey oil pipeline were zoned in more detail. It makes it possible to predict the scale and areas most susceptible to negative impact in the event of an accidental oil spill, and to make the necessary decisions for the location of the spill response facilities, as well as the facilities themselves, already at the stage of selection and design of the pipeline route.

AbstractA new strategy of selective DNA target modification was proposed. The using of reactive derivatives of short oligonucleotides in the presence of flanking effector pair allows one to modify DNA target only when the perfect complementary complex of DNA target and oligonucleotide tandem is formed.

AbstractDirected cleavage of RNA phosphodiester bonds by peptidyloligodeoxyribonucleotide containing the peptide residues with the alternated hydrophobic and basic amino acids was demonstrated.

The kinetics of the N-oxidation with perbenzoic acid of 15 derivatives of quinoline and benzoquinoline in chloroform and 19 compounds in 50% aqueous dioxane at 20, 25, 30, and 35 °C were subjected to a comparative study. The rate constants, parameters of the Arrhenius equation, and the activation energies for the N-oxidation of the indicated monoazines were determined. A scale of the reactivities of derivatives of the quinoline series and benzoquinolines was calculated within the framework of general perturbation theory.

The bromination of pyridine in the form of complexes with some Lewis acids and in the presence of catalytic amounts of the latter was studied. It is shown that bromination takes place readily at ∼100 °C in the presence of catalysts such as AlCl3, ZnCl2, CuCl2, SbCl3, InCl3, TeCl4, and HgCl2. The principal bromination products are 3-bromopyridine and 3,5-dibromopyridine. The problem of the possibility of so-called π back-bonding in the case of elements of the higher periods (particularly In, Te, and Sb) is discussed.

Abstract: A comparative study of the kinetics of the N oxidation of 19 derivatives of the pyridine series with perbenzoic acid in chloroform and aqueous dioxane at 20, 25, 30, and 35 C was made. The rate constants, the parameters of the Arrhenius equation, and the activation energies of the N oxidation of the indicated monoazines were determined. The scale of the reactivities of the derivatives of the pyridine series was calculated within the framework of the Pearson hard-soft acid-base concept.

On the basis of our own results and literature data it is concluded thatvC=C and the stability of surface π-complexes of olefins with transition metal ions are governed by the nature of metal and its valence state.

AbstractThe influence of an effector (di-N-(2-hydroxyethyl)-phenazinium derivative of oligonucleotide) on modification of the DNA target by alkylating derivatives of oligonucleotides having various hybridization properties was studied. Being adjacent to the alkylating group of the reagent, the effector enhances the target modification if the oligonucleotide reagent has low hybridization properties and suppresses the modification if the reagent can form the stable complex with the DNA target at the used conditions.FAX: 007 3832 35 16 65; e-mail: zarytova@niboch.nsc.ru

AbstractRecently, a new approach has been proposed to improve the site-specificity and efficiency of the modification of nucleic acid target sequences, the binary system of complementary-addressing nucleic acid sequences. The binary system comprises two oligonucleotides, one modified with a photosensitizing group and the other with a photoreactive group. The sites of chemical modification are arranged to bring the two chemical functions close enough together in space to allow efficient energy transfer from the photo-excited photosensitizer to an arylazide moiety which expels N2to form a nitrene which subsequently covalently labels the target nucleic acid. Structural analysis performed by high-resolution 2D NMR spectroscopy (400 MHz and 600 MHz) are reported for the model binary system 1:2:3, where 1is the target 12-mer pdGTATCAGTTTCT, 2is a photoactivatable fluoroazide derivative dAGAAACp-L-Azand 3is the photosensitizer derivative Pyr-pdTGATAC (here: Azis the p-azidotetrafluorobenzyl group, Pyrthe pyrenyl-l-methylamino group, La linker group). The assignment of oligonucleotide and modifying group protons was performed using 1H COSY, TOCSY and NOESY experiments. Comprehensive analysis of 1H NOESY spectra of 1:2:3showed that terminal fragments of the complex [5′p-1T-2G-3A-4T-], [-21A-22T-23A-24C], [-8T-9T-10T-11C- 12T] and [13A-14G-15A-15A-17A-18C-] gave a continuous set of intra- and inter-nucleotide interactions, typical of regular double-stranded B-DNA. In contrast, the central region of the complex composed of 5C, 6A, 7G, 19T and 20G nucleotide residues, nearest the Pyr and Az groups, was found to be distorted. Thus some signals from aromatic and/or sugar-ring protons of the above nucleotide residues were extremely broadened or almost absent. Moreover, some intra- and/or inter-nucleotide interactions, typical of the regular DNA duplex, were not detected for the [-5C-6A-7G-] and [-19T-20G-] regions of the tandem system. Instead of that, some cross-peaks of low-intensity between the H2 proton of the Pyrgroup and 7G(H1′), 7G(H2′/H2”), 7G(H3′), 4T(H2”), 4T(H4′) and 4T(H5′/H5”) were observed. Additional 1H -1H NOE-interactions between methylene protons of the linker group Land some sugar ring protons of 18C nucleotide residue were detected. A preliminary structural model, constructed using proton-proton distances between Pyrand the DNA and Az-Land DNA obtained from a 1H NOESY experiment at 300 ms mixing time as constraints for the refinement of the structure, displayed significant distortion from B-DNA of the double-stranded helix in the middle of the complex, (-5C-6A-7G, -18C-19T-20G-). The Pyrgroup was located in what remains of the minor groove near 4T, 5C, 6A and 7G and the centroid of the azide ring less than 9A° from the centroid of the ring system of Pyrgroup.

Without Abstract:

Conclusions 1.Hemolymph from donor snails conditioned to refuse food facilitates the development of refusal of the same type of food in intact recipients. Hemolymph of pseudoconditioned donors inhibits conditioning in recipients.2.The facilitating effect manifests itself variously depending on the type of conditioned stimulus (preferred or nonpreferred food) and the amount of injected hemolymph. At certain doses the facilitating effect gives way to an inhibitory effect.3.Facilitation of conditioning is of a seasonal nature.

Conclusions 1.Both a specific and a nonspecific (with regard to the type of conditioned stimulus) component are found to exist in the neurohumoral link of the mechanisms of formation and consolidation of the conditioned response of food refusal in the snail.2.The specific component is revealed only for selection of the optimal conditions with regard to the type of conditioned stimulus, the dose of hemolymph, and the season.3.When the parameters of the experiment are nonoptimal, either there is a prevalence of the nonspecific component, facilitating conditioning, or the facilitatory effect gives way to an inhibitory effect.

Conclusions 1.The combination of rhythmic lifting of one forelimb and simultaneous continuous pressor stimulation of the same limb in cats leads to the formation of a conditioned motor reflex to time. Trace motor responses in the assigned rhythm can be detected either during continuous pressor stimulation or during micropolarization of the sensomotor or motor cortex, the body of the caudate nucleus, corpus callosum, and mesencephalic reticular formation by currents of 0.3–1.5 µA.2.A combination of rhythmic lifting of the forelimb with continuous micropolarization of the sensomotor cortex in the region of representation of the lifted limb by a current of 0.5–1.5 µA also leads to formation of a conditioned reflex to time. Trace motor responses are detected to continuous micropolarization of this same cortical area alone or to subthreshold pressor stimulation of the trained limb alone.3.It is suggested that these phenomena may have a common physiological mechanism: prolonged activation (through pressor stimulation or micropolarization) of sensory and motor cortical projections of the proprioceptive stimulus facilitates the formation of a trace reflex, such as a conditioned reflex to time.