[Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression]. / Epitelial'no-stromal'nye vzaimodeistviya v adenokartsinome podzheludochnoi zhelezy: rol' stromy v progressirovanii zabolevaniya.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

[Botulinum therapy of spastic forms of cerebral palsy in various locomotor patterns]. / Botulinoterapiya spasticheskikh form detskogo tserebral'nogo paralicha pri razlichnykh lokomotornykh patternakh.

Spasticity in patients with cerebral palsy (CP) is the main impediment to normal locomotion. The function of the Central Pattern Generator (CPG), i.e. a group of neural chains in the spinal cord, stands at the core of any rhythmical movement. CPG can generate locomotion patterns without supraspinal control, which can have both positive and negative impact on the ability to move. Performing the motor tasks such as walking, running and swimming, creates the consistent rhythmical movement of legs and arms through interaction between CPGs of upper and lower extremities. This interaction can cause the activation of pathological movement patterns in lower extremities in response to upper limb spasticity. Thus, neural chains in the spinal cord become the generator of pathologically increased excitation which has developed as a result of a focal lesion in the CNS. All the statements described above show the importance of introducing the upper limb injections of bFotulinum toxin A in the protocol in order to develop normal locomotion. The PUL study approved the optimal level of efficacy and favourable safety profile of botulinum toxin A in children with CP and upper limb muscle spasticity.

Diagnosing sub-acute rumen acidosis in cows in the post-calving period with digital technologies / [Diagnóstico de acidose ruminal subaguda em vacas no período pós-parto usando tecnologias digitais]

This study aims to determine the relationship between indicators of the motor activity, pH factor, rumen and rectal temperature within 10 days after calving and to analyze the possibility of using the studied parameters as prognostic signs for diagnosing sub-acute rumen acidosis (SARA). The measurements were taken using bolus with sensors designed to monitor cow health. The motor activity, pH factor and ruminal temperature of 10 cows were measured during 10 days at a measurement interval of every 60 seconds. Next, the researchers calculated the average values of the obtained readings, which were divided into 2 groups according to a measurement interval of every 12 hours. Rectal temperature was measured using a veterinary thermometer every 12 hours (at 8 a.m. and at 8 p.m.). As a result, 200 measurements were obtained. Descriptive sampling statistics were calculated using the SPSS Statistics program. An increase in motor activity reduces the pH level of the rumen environment. Lowering the pH factor of the rumen environment leads to an increase in ruminal temperature. There is a positive statistically significant correlation between ruminal and rectal temperature. The nosology of SARA can be predicted by measuring the motor activity and rectal temperature of dairy cows.(AU)

Este estudo visa determinar a relação entre indicadores de atividade motora, fator de pH, temperatura ruminal e retal em até 10 dias após o parto e analisar a possibilidade de utilizar os parâmetros estudados como sinais prognósticos para o diagnóstico de acidose ruminal subaguda (SARA). As medições foram feitas usando bolus com sensores projetados para monitorar a saúde das vacas. A atividade motora, o fator de pH e a temperatura ruminal de 10 vacas foram medidos durante 10 dias em intervalos de medição de 60 segundos. A seguir, os pesquisadores calcularam os valores médios das leituras obtidas, que foram divididos em 2 grupos de acordo com um intervalo de medição a cada 12 horas. A temperatura retal foi medida com um termômetro veterinário a cada 12 horas (às 8h e às 20h). Como resultado, foram obtidas 200 medições. As estatísticas de amostragem descritiva foram calculadas usando o programa SPSS Statistics. Um aumento na atividade motora reduz o nível de pH do ambiente ruminal. A redução do fator de pH do ambiente ruminal leva a um aumento da temperatura ruminal. Existe uma correlação positiva estatisticamente significativa entre a temperatura ruminal e retal. A nosologia com SARA pode ser prevista medindo a atividade motora e a temperatura retal de vacas leiteiras.(AU)

The effect of energy-dependent electron scattering on thermoelectric transport in novel topological semimetal CoSi.

Cobalt monosilicide and its solid solutions with Fe or Ni crystallize in B20 cubic noncentrosymmetric structure. These compounds have long been known as promising thermoelectric materials. Recently it was revealed, that they also have unconventional electronic topology. This renewed interest to the investigation of their transport properties. In order to improve theoretical description of thermoelectric transport in these compounds, we take into account electron scattering beyond commonly used constant relaxation time approximation. Using first principle calculations, we investigate the scattering of charge carriers by phonons and point defects. The dependence of the scattering rate on the energy correlates with that for the total density of states. This implies that in this material not only the intraband, but also the interband scattering is important, especially for bands with low density of states. The Seebeck coefficient and the electrical resistivity of CoSi and of dilute solid solutions Co1-x M x Si (M = Fe or Ni, x < 0.1) are calculated as a function of temperature and the alloy composition. We show that the account of strong energy dependence of relaxation time is important for the description of experimentally observed rapid increase of the resistivity and qualitative change of its temperature dependence with the substitution of cobalt for iron, as well as for the description of the magnitude of the Seebeck coefficient, its temperature and composition dependence.

Band structure and unconventional electronic topology of CoSi.

Semimetals with certain crystal symmetries may possess unusual electronic structure topology, distinct from that of the conventional Weyl and Dirac semimetals. Characteristic property of these materials is the existence of band-touching points with multiple (higher than two-fold) degeneracy and nonzero Chern number. CoSi is a representative of this group of materials exhibiting the so-called 'new fermions'. We report on an ab initio calculation of the electronic structure of CoSi using density functional methods, taking into account the spin-orbit interactions. The linearized [Formula: see text] Hamiltonian, describing the anisotropic electronic structure of CoSi near the Γ point is derived. The topological features of band-touching nodes with four- and six-fold degeneracy located at the Γ and R points in the first Brillouin zone are analysed using the linearized Hamiltonians and first principle calculations. In particular, we show, using the non-Abelian Berry curvature, that these band-touching points carry topological charges of [Formula: see text], which change signs at certain values of parameters of the Hamiltonians. We describe the resulting Fermi arc surface states and their spin texture. We also discuss the influence of many body [Formula: see text] corrections on the electronic band structure and the topological properties of CoSi.

The detection of hepatitis c virus core antigen using afm chips with immobolized aptamers.

In the present study, the possibility of hepatitis C virus core antigen (HCVcoreAg) detection in buffer solution, using atomic force microscope chip (AFM-chip) with immobilized aptamers, has been demonstrated. The target protein was detected in 1mL of solution at concentrations from 10-10М to 10-13М. The registration of aptamer/antigen complexes on the chip surface was carried out by atomic force microscopy (AFM). The further mass-spectrometric (MS) identification of AFM-registered objects on the chip surface allowed reliable identification of HCVcoreAg target protein in the complexes. Aptamers, which were designed for therapeutic purposes, have been shown to be effective in HCVcoreAg detection as probe molecules.

Serologic Markers of Autism Spectrum Disorder.

According to WHO data, about 67 million people worldwide are affected by autism, and this number grows by 14% annually. Among the possible causes of autism are genetic modifications, organic lesions of the central nervous system, metabolic disorders, influence of viral and bacterial infections, chemical influence to the mother's body during pregnancy, etc. The conducted research shows that research papers published until today do not name any potential protein markers that meet the requirements of the basic parameters for evaluating the efficiency of disease diagnostics, in particular high sensitivity, specificity, and accuracy. Conducting proteomic research on a big scale in order to detect serologic markers of protein nature associated with development of autism spectrum disorders seems to be highly relevant.

Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics.

BACKGROUND: In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it. METHODS: We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders". RESULTS: On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/µL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04). CONCLUSION: Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.

Atomic Force Microscopy Study of Protein-Protein Interactions in the Cytochrome CYP11A1 (P450scc)-Containing Steroid Hydroxylase System.

Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) were used for monitoring of the procedure for cytochrome CYP11A1 monomerization in solution without phospholipids. It was shown that the incubation of 100 µM CYP11A1 with 12% Emulgen 913 in 50 mM KP, pH 7.4, for 10 min at T = 22°C leads to dissociation of hemoprotein aggregates to monomers with the monomerization degree of (82 ± 4)%. Following the monomerization procedure, CYP11A1 remained functionally active. AFM was employed to detect and visualize the isolated proteins as well as complexes formed between the components of the cytochrome CYP11A1-dependent steroid hydroxylase system. Both Ad and AdR were present in solution as monomers. The typical heights of the monomeric AdR, Ad and CYP11A1 images were measured by AFM and were found to correspond to the sizes 1.6 ± 0.2 nm, 1.0 ± 0.2 nm and 1.8 ± 0.2 nm, respectively. The binary Ad/AdR and AdR/CYP11A1mon complexes with the heights 2.2 ± 0.2 nm and 2.8 ± 0.2 nm, respectively, were registered by use of AFM. The Ad/CYP11A1mon complex formation reaction was kinetically characterized based on optical biosensor data. In addition, the ternary AdR/Ad/CYP11A1 complexes with a typical height of 4 ± 1 nm were AFM registered.

Ballistic thermoelectric transport in a Luttinger liquid.

The Seebeck and Peltier coefficients of a homogeneous Luttinger liquid are calculated in the ballistic regime. Nonlinearity of the electron spectrum is taken into account. It is shown that, in the framework of the defined approximations, the thermoelectric power of a Luttinger liquid is equal to zero, in agreement with the exponentially small thermopower of a one-dimensional degenerate Fermi gas. The Peltier coefficient is controlled by a nonequilibrium state of the system. It is finite and renormalized by the interaction in the case of a convective flow of a Luttinger liquid. The zero modes of bosonic excitations and the dispersion-induced contribution to the electric current operator are taken into account in calculations.

Isatin interaction with glyceraldehyde-3-phosphate dehydrogenase, a putative target of neuroprotective drugs: partial agonism with deprenyl.

There is evidence that the binding of deprenyl, a monoamine oxidase (MAO) B inhibitor, and other propargylamines to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is primarily responsible for their neuroprotective and antiapoptotic effects. Thus, GAPDH may be a target for other neuroprotective drugs. Using two independent approaches, radioligand analysis and an optical biosensor technique, we demonstrate here that GAPDH also interacts with the endogenous, reversible MAO B inhibitor, isatin. Deprenyl inhibited both [3H]isatin binding to GAPDH, and the binding of this enzyme to an isatin analogue, 5-aminoisatin, immobilized on to an optical biosensor cell. Another MAO inhibitor, tranylcypromine, was ineffective. Both deprenyl and isatin inhibited GAPDH-mediated cleavage of E. coli tRNA, and their effects were not additive. We suggest that isatin may be an endogenous partial functional agonist of deprenyl in its effect on GAPDH and GAPDH-mediated RNA cleavage. Changes in level of endogenous isatin may influence the neuroprotective effect of deprenyl in vivo.

Melting and heating of two-dimensional Coulomb clusters in dusty plasmas.

The heating and melting of two-dimensional dust clusters with one additional particle in the lower layer has been investigated experimentally in a gas discharge. The full dynamical properties of the system during the entire phase transition were determined in terms of the spectral power densities of the crystal modes. A two-step melting transition is identified when the gas pressure in the discharge is reduced: first, a sudden increase of the dust temperature takes place due to an instability of the lower-layer particle resulting in a hot crystalline state of the cluster, and second, the actual transition into a fluid state is observed at a decisively lower gas pressure.

Epizootiological control of bluetongue disease in Bulgaria in 2002.

In accordance with the National Surveillance Programme for the control of bluetongue (BT) disease in 2002, serum surveillance was performed in 22 sentinel, seronegative animal herds located in western Bulgaria. These herds were at least 40 km outside the settlements affected by the 2001 epidemic. Another 42 sentinel villages (herds) were established in southern Bulgaria in a 10 km border strip zone in the Bourgas, Yambol, Haskovo, Kardjali, Smolyan and Blagoevgrad Districts. The implementation of the programme in 2002 commenced on 15 April and continued until 15 November. More than 7 200 serum samples were tested prior to 26 August and no evidence of active BT virus (BTV) infection detected. This was confirmed by further viral, serological, epidemiological and clinico-pathological observations. In addition, there was no evidence of transborder penetration of BTV into Bulgaria by infected livestock or by infected Culicoides. However, on 26 August 2002, BTV seropositive sentinel animals were detected close to the southern Bulgarian border. Subsequently, animals were detected in more than 20 villages, but clinical disease was not observed. Bulgaria was divided into 58 quadrants (50 km x 50 km) and a Culicoides surveillance programme established in 23 of these. A total of 92 Culicoides light-trap collections were made. During three years of Culicoides surveillance, not a single specimen of the principal BT vector C. imicola was captured. The dominant Culicoides species was C. obsoletus, followed by C. pulicaris and C. punctatus; in August 2001, C. puncticollis was recorded for the first time. Studies on the seasonal phenology of Culicoides were conducted in two villages (Vacsevo and Bersin in the District of Kiustendil) affected in the 2001 outbreak of BT. Here trapping of Culicoides commenced on 1 March 2002 and continued until 15 November 2002; midges became active during the third week of April to almost cease in the second half of November. There appeared to be three peaks of activity: one during the second half of May, another in August and a third at the beginning of October.

Analysis of bispecific monoclonal antibody binding to immobilized antigens using an optical biosensor.

The interaction between two different monoclonal antibodies (Mabs) and their corresponding bispecific antibodies (Babs) with immobilized antigens was investigated using an optical biosensor (IAsys). The analyzed panel of affinity-purified antibodies included two parental Mabs (one of which was specific to human IgG (hIgG), and another one to horseradish peroxidase (HRP)), as well as Babs derived thereof (anti-hIgG/HRP). Babs resulting from the fusion of parental hybridomas bear two antigen-binding sites toward two different antigens and thus may interact with immobilized antigen through only one antigen-binding site (monovalently). Using an IAsys biosensor this study shows that the bivalent binding of Mabs predominates over the monovalent binding with immobilized HRP, whereas anti-hIgG parental Mabs were bound monovalently to the immobilized hIgG. The observed equilibrium association constant (K(ass)) values obtained in our last work [1] by solid-phase radioimmunoassay are consistent with those constants obtained by IAsys. The K(ass) of anti-HRP Mabs was about 50 times higher than that of anti-HRP shoulder of Babs. The dissociation rate constant (k(diss)) for anti-HRP shoulder of Babs was 21 times higher than k(diss) for anti-HRP Mabs. The comparison of the kinetic parameters for bivalent anti-HRP Mabs and Babs derived from anti-Mb/HRP and anti-hIgG/HRP, allowed to calculate that 95% of bound anti-HRP Mabs are bivalently linked with immobilized HRP, whereas only 5% of bound anti-HRP Mabs are monovalently linked. In general, the data obtained indicate that Babs bearing an enzyme-binding site may not be efficiently used instead of traditional antibody-enzyme conjugates in the case of binding of bivalent Mabs.

A qualitative assessment of the risk of introducing foot and mouth disease into Russia and Europe from Georgia, Armenia and Azerbaijan.

A qualitative risk assessment was performed to evaluate the risk of introducing foot and mouth disease (FMD) virus into Russia and the rest of Europe from the countries of Transcaucasia (Armenia, Azerbaijan and Georgia). The assessment was based on data collected during a three-week mission to these countries by the Food and Agriculture Organization, the European Union and the Office International des Epizooties in March 1999. Due to the strong involvement of the local veterinary services, much information was obtained. Although the data were not sufficient to allow a quantitative risk assessment to be performed, the investigation served as a useful initial approach, prior to undertaking a quantitative risk assessment. The risk of FMD virus infection is a function of two elements, namely: the probability of the hazard (virus infection) occurring, and the magnitude of the consequences. The probability of the hazard occurring is the product of the probability of entry of the virus and the probability of exposure to the virus. These elements were assessed using the following parameters: prevalence of infection; volume of trade; capacity of the virus to survive; and potential for infection. The magnitude of the consequences is derived from the probability of transmission and spread. Combining these parameters, the probability of occurrence of the hazard was rated as 'moderate'. Economic consequences of potential transmission and spread of FMD, in the local context, were rated as 'negligible'. As a result, the overall risk of introducing FMD virus into Russia and the rest of Europe from Trancaucasia was rated as 'low' at the time of evaluation. The method and results are presented to serve as a basis for further discussion.

Revelation of ternary complexes between redox partners in cytochrome P450-containing monooxygenase systems by the optical biosensor method.

Formation of binary and ternary complexes in the water-soluble cytochrome P450cam (P450cam)-containing as well as in the membrane P4502B4(2B4)- and the mixed P450scc-containing monooxygenase systems was investigated in real time by the 'resonant mirror' optical biosensor method. It was shown that the inter-protein electron transfer occurs not only during complex formation but also upon random collision--as was the case with the d-Fp/d-b5 pair (2B4 system). Binary complexes may be either facilitative to electron transfer (electron-transfer complexes) or prohibitive to it (non-productive complexes). Although the binary PdR/Pd and P450cam/Pd complex formation (within the P450cam-system) as well as the binary AdR/Ad and P450scc/Ad complex formation (within the P450scc-system) does occur, the lifetimes of these complexes formed are several orders of magnitude higher than the time required for realization of a complete hydroxylation cycle. At the same time, the lifetimes of the ternary PdR/Pd/P450cam and AdR/Ad/P450scc complexes are sufficient to permit the realization of a complete hydroxylation cycle in either of these systems. For the membrane P450 2B4 system, the formation of both the binary (Fp/2B4 and 2B4/b5) and ternary (Fp/2B4/b5) complexes was registered. The lifetimes of the binary Fp/2B4 and the ternary Fp/2B4/b5 complexes are sufficient for realization of a complete hydroxylation cycle in each of them.

High-efficiency beam extraction and collimation using channeling in very short bent crystals.

A silicon crystal was used to channel and extract 70 GeV protons from the U-70 accelerator with an efficiency of 85.3+/-2.8%, as measured for a beam of approximately 10(12) protons directed towards crystals of approximately 2 mm length in spills of approximately 2 s duration. The experimental data follow very well the prediction of Monte Carlo simulations. This demonstration is important in devising a more efficient use of the U-70 accelerator in Protvino and provides crucial support for implementing crystal-assisted slow extraction and collimation in other machines, such as the Tevatron, RHIC, the AGS, the SNS, COSY, and the LHC.

Molecular recognition in the p450cam monooxygenase system: direct monitoring of protein-protein interactions by using optical biosensor.

A real-time optical biosensor study on the interactions between putidaredoxin reductase (PdR), putidaredoxin (Pd), and cytochrome P450cam (P450cam) within the P450cam system was conducted. The binary Pd/P450cam and Pd/PdR complexes were revealed and kinetically characterized. The dominant role of electrostatic interactions in formation of productive electron transfer complexes was demonstrated. It was found that Pd/P450cam complex formation and decay obeys biphasic kinetics in contrast to the monophasic one for complexes formed by other redox partners within the system. Evidence for PdR/P450cam complex formation was obtained. It was found that, in contrast to Pd, which binds only to its redox partners, PdR and P450cam were able to form PdR/PdR and P450cam/P450cam complexes. A ternary PdR/Pd/P450cam complex was also registered. Its lifetime was sufficient to permit up to 60 turnovers to occur. The binding of Pd to P450cam and to PdR within the ternary complex occurred at distinct sites, with Pd serving as a bridge between the two proteins.

Soil- and plant-based countermeasures to reduce 137Cs and 90Sr uptake by grasses in natural meadows: the REDUP project.

The effectiveness of a set of soil- and plant-based countermeasures to reduce 137Cs and 90Sr transfer to plants was tested in natural meadows in the area affected by Chernobyl fallout. Countermeasures comprised the use of agricultural practices (disking + ploughing, liming and NPK fertilisation), addition of soil amendments and reseeding with a selection of grass species. Disking + ploughing was the most effective treatment, whereas the K fertiliser doses applied were insufficient to produce a significant increase in K concentration in soil solution. The application of some agricultural practices was economically justifiable for scenarios with a high initial transfer, such as 137Cs-contaminated organic soils. The use of soil amendments did not lead to a further decrease in transfer. Laboratory experiments demonstrated that this was because of their low radionuclide sorption properties. Finally, experiments examining the effect of plant species on radionuclide transfer showed that both transfer and biomass can depend on the plant species, indicating that those with high radionuclide root uptake should be avoided when reseeding after ploughing.