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Background: In humans, figurate erythema (FE) represents a heterogenous group of dermatoses with circular or serpiginous erythematous skin lesions; FE has not been reported in cats. Objectives: To report clinical and histological characteristics and outcomes of FE in sphynx cats from Baltic sea‐bordering countries. Animals: Eleven client‐owned sphynx cats with FE. Materials and Methods: We recruited cases meeting the following criteria: (i) a sphynx breed, (ii) FE with or without scaling, (iii) a chronic, waxing‐and‐waning course lasting longer than a month and (iv) an absence of other skin diseases. Results: Of 11 cats, there were seven Donskoys, one Peterbald, one Ukrainian Levkoy and two presumed Canadian sphynxes; all except one were males, and the age of onset was <12 months in eight cats. Skin lesions lasted between 1.2 and 56 months, and they consisted of erythematous plaques with a linear‐to‐serpiginous, annular, gyrate or iris configuration predominating on the trunk and extremities. Scaling was often seen trailing the edge of the centrifugally expanding erythema. All cats were otherwise asymptomatic or mildly pruritic. Dermatophytosis was ruled out by special stains and/or fungal cultures in eight cats. Microscopic lesions revealed focal, mild‐to‐moderate epidermal hyperplasia and hyperkeratosis, minimal‐to‐mild dysplasia and subepidermal collagen smudging. Special stains were negative for dermatophytes. The clinical remission of FE was not achieved with diet changes or medical interventions; yet, a spontaneous, transient, partial or complete improvement occurred in most cats. Conclusion and Clinical Relevance: This is the first report of FE in sphynx cats from Eastern Europe. [ABSTRACT FROM AUTHOR]

The article proposes a criterion for the existence of sliding processes according to the frequency characteristics of the control device and the control object. It is shown that the conditions for the existence of slip are equivalent to the conditions for the absolute stability of equivalent circuits of the original systems with a variable structure. This approach is proposed by the authors as an alternative to the method of phase trajectories and state space equations used by other researchers. Frequency criteria make it possible to formulate several practical engineering provisions that are very important for the implementation of this control method in real electric drives. The main conclusions are confirmed by simulation of both processes in systems with a variable structure and in equivalent circuits. [ABSTRACT FROM AUTHOR]

According to the Cancer Genome Atlas (TCGA), gastric cancers are classified into four molecular subtypes: Epstein–Barr virus-positive (EBV+), tumors with microsatellite instability (MSI), tumors with chromosomal instability (CIN), and genomically stable (GS) tumors. However, the gastric cancer (GC) with chromosomal instability remains insufficiently described and does not have effective markers for molecular and histological verification and diagnosis. The CIN subtype of GC is characterized by chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells. Structural rearrangements in the CIN subtype of GC are not accidental and are commonly detected in chromosomal loci, being abnormal because of specific structural organization. The causes of CIN are still being discussed; however, according to recent data, aberrations in the TP53 gene may cause CIN development or worsen its phenotype. Clinically, patients with the CIN subtype of GC demonstrate poor survival, but receive the maximum benefit from adjuvant chemotherapy. In the review, we consider the molecular mechanisms and possible causes of chromosomal instability in GC, the common rearrangements of chromosomal loci and their impact on the development and clinical course of the disease, as well as the driver genes, their functions, and perspectives on their targeting in the CIN subtype of GC. [ABSTRACT FROM AUTHOR]

Stability and narrow size distribution are among the main requirements that apply to drug formulations based on polymeric nanoparticles. In this study, we obtained a series of particles based on biodegradable poly(D,L-lactide)-b-poly(ethylene glycol) (P(D,L)LAn-b-PEG113) copolymers with varied hydrophobic P(D,L)LA block length n from 50 to 1230 monomer units stabilized by poly(vinyl alcohol) (PVA) by a simple "oil-in-water" emulsion method. We found that nanoparticles of P(D,L)LAn-b-PEG113 copolymers with relatively short P(D,L)LA block (n ≤ 180) are prone to aggregate in water. P(D,L)LAn-b-PEG113 copolymers with n ≥ 680 can form spherical unimodal particles with values of hydrodynamic diameter less than 250 nm and polydispersity less than 0.2. The aggregation behavior of P(D,L)LAn-b-PEG113 particles was elucidated in terms of tethering density and conformation of PEG chains at the P(D,L)LA core. Docetaxel (DTX) loaded nanoparticles based on P(D,L)LA680-b-PEG113 and P(D,L)LA1230-b-PEG113 copolymers were formulated and studied. It was observed that DTX-loaded P(D,L)LAn-b-PEG113 (n = 680, 1230) particles are characterized by high thermodynamic and kinetic stability in aqueous medium. The cumulative release of DTX from the P(D,L)LAn-b-PEG113 (n = 680, 1230) particles is sustained. An increase in P(D,L)LA block length results in a decrease in DTX release rate. The in vitro antiproliferative activity and selectivity studies revealed that DTX-loaded P(D,L)LA1230-b-PEG113 nanoparticles demonstrate better anticancer performance than free DTX. Favorable freeze-drying conditions for DTX nanoformulation based on P(D,L)LA1230-b-PEG113 particles were also established. [ABSTRACT FROM AUTHOR]

[Display omitted] The effect of crystallization of a hydrophobic poly(lactide) block on the self-organization of biocompatible and biodegradable amphiphilic poly(lactide)- block -poly(ethylene oxide) (PLA- b -PEO) copolymers in a dilute aqueous solution has been investigated. It was demonstrated that the co-crystallization of poly(L,L-lactide) [P(L,L)LA] and poly(d,d-lactide) [P(d,d)LA] chains under equimolar mixing of P(L,L)LA 46 - b -PEO 113 and P(d,d)LA 56 - b -PEO 113 copolymers resulted in the formation of stable and spontaneously water-redispersible stereocomplex micelles with semicrystalline P(L,L)LA/P(d,d)LA cores. It was shown that the P(L,L)LA 46 / P(d,d)LA 56 - b -PEO 113 stereo-complex micelles produced by dialysis can be potential vehicles for the anticancer agent oxaliplatin [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of IL6, IL6R, TNFRSF1A, CTLA4, IL10, IL23R, and PADI4; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes (IL1B, IL17A, PADI4, DHODH, GLCCI1, IL23R, and TNFAIP3), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel. [ABSTRACT FROM AUTHOR]

The molecular cloud Sgr B2 is a natural Compton mirror in the Central Molecular Zone. It is believed that the observed fading of the Sgr B2 X-ray emission in continuum and the Fe Kα 6.4 keV line indicates past X-ray flare activity of the supermassive black hole Sgr A⋆. Sgr B2 was investigated by the INTEGRAL observatory in the hard X-ray in 2003–2009, showing clear decay of its hard X-ray emission. In this work, we present a long-term time evolution of the Sgr B2 hard X-ray continuum after 2009, associated with the hard X-ray source IGR J17475−2822 as observed by INTEGRAL. The 30–80 keV sky maps, obtained in 2009–2019, demonstrate a significant excess spatially consistent with IGR J17475−2822. The observed 2003–2019 light curve of IGR J17475−2822 is characterized by a linear decrease by a factor of ∼2 until 2011, after which it reaches a constant level of ∼1 mCrab. The source spectrum above 17 keV is consistent with a power-law model with Γ = 1.4 and a high-energy cut-off at ∼43 keV. The Sgr B2 residual emission after ∼2011 shows a good correspondence with models of X-ray emission due to the irradiation of the molecular gas by hard X-rays and low-energy cosmic ray ions. We discuss the possible origin of the residual Sgr B2 emission after 2011 within these models, including theoretically predicted multiply scattered emission. [ABSTRACT FROM AUTHOR]

Cell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications. In the present study, the frequencies of abnormal promoter hypermethylation in BC were 13% for ITGA1, 31% for ITGA4, 4% for ITGA7, 39% for ITGA9, 38% for NID1, and 41% for NID2. ITGA2, ITGA3, ITGA6, ITGB1, and DAG1 promoters were nonmethylated in normal and BC samples. ITGA4, ITGA9, and NID1 promoter hypermethylation was associated with the HER2 positive tumors, and promoter hypermethylation of ITGA1, ITGA9, NID1 and NID2 was associated with a genome-wide CpG island hypermethylated BC subtype. Given that ITGA4 is not expressed in normal breast, one might suggest that its abnormal promoter hypermethylation in cancer is non-functional and is thus merely a passenger epimutation. Yet, this assumption is not supported by our finding that it is not associated with a hypermethylated BC subtype. ITGA4 acquires expression in a subset of breast carcinomas, and methylation of its promoter may be preventive against expression in some tumors. Strong association of abnormal ITGA4 hypermethylation with the HER2 positive tumors (p = 0.0025) suggests that simultaneous presence of both HER2 and integrin α4 receptors is not beneficial for tumor cells. This may imply HER2 and integrin α4 signaling pathways interactions that are yet to be discovered. [ABSTRACT FROM AUTHOR]

The characteristics of power sources affect the performance of autonomous electrically driven systems, such as unmanned aerial vehicles, aircraft missiles, guided bombs, torpedoes, space and aerospace vehicles, controlled gliding parachutes. The creation of control systems for the aircraft flight control surfaces of autonomous mobile objects is an urgent topic in modern research. This article provides how a mathematical model based on integrated approach is developed for an energy-efficient mechatronic module for control systems of promising mobile objects powered by various current sources; a comparison of the energy and dynamic characteristics of mechatronic modules of promising mobile objects for various power options is made. As a result, a new type of integrated power-supply source based on capacitive energy storage with floating charge from a primary chemical source of current has been developed. The proposed approaches, dependencies and algorithms can be used in the design of highly efficient mechatronic control algorithms for autonomous mobile objects of a new generation. [ABSTRACT FROM AUTHOR]

This work investigates the effect of carbon nanomodification on the residual stress-strain state (SSS) after molding. One of the ways to reduce residual stresses and deformities is nanomodification. The main objective was to determine the degree of influence of the nanomodification parameters on the residual SSS. Within the framework of this study, 4 slabs were made. Two slabs are made of a conventional binder with laying [010/9010] and [010/4510] and two slabs of a modified binding material with the same layer structure. For the fabricated plates, deflections were measured on each of the four sides, during which residual strains were obtained in the panels of nanomodified carbon fiber for the considered layings with and without modified binding material. To analyze the residual stress-strain state, a numerical and analytical calculation was performed. The numerical calculation was carried out by means of the finite element method for the case when the slab is fixed at the point of the geometric center, with no power load, and the temperature load is a difference of 100 °C. An analytical calculation was carried out for the case when the slab is free from fastening and external power load, and the temperature load is a difference of 100°C. During the study, variants of the physicomechanical properties of the monolayer were obtained using the Digimat software and the Mori-Tanaka averaging method. The results obtained by analytical and numerical methods have a good correlation between each other, and in the course of comparison with the experiment, a method for calculating the characteristics of the monolayer that was closest to the experimental result was determined. On the basis of the obtained results, conclusions were made on the possibility of reducing residual SSS and deformation in structures with asymmetric reinforcement schemes using a matrix containing carbon nanoparticles. [ABSTRACT FROM AUTHOR]

In this work, we present the first detailed analysis of the supernova remnant RX J1713.7–3946 in the hard X-ray energy range with the Imager on Board the INTEGRAL Satellite (IBIS) coded-mask telescope onboard the INTEGRAL observatory. The shell-type morphology of the entire remnant is mapped in hard X-rays for the first time and significantly detected up to 50 keV. The IBIS sky image of RX J1713.7–3946, accumulated over 14 yr of operations, demonstrates two extended hard X-ray sources. These sources are spatially consistent with north-west and south-west rims of RX J1713.7–3946 and are also clearly visible at energies below 10 keV with XMM–Newton. This points to a single emission mechanism operating in soft and hard X-rays. The INTEGRAL 17–120 keV spectrum of RX J1713.7–3946 is characterized by a power-law continuum with the photon index of Γ ≈ 3 that is significantly softer than Γ ≈ 2 determined by XMM–Newton in the 1–10 keV energy range, suggesting a progressive steepening of the spectrum with the energy. [ABSTRACT FROM AUTHOR]

Currently, methods of three-dimensional printing of products from polymer, metal and ceramic materials are widely used. Layer-by-layer synthesis technologies make it possible to obtain high-quality products with sufficiently high mechanical characteristics close to those realized using traditional technological processes. A related problem is solved, including calculating the temperature in the product and the operation area surrounding it in a flat setting based on two different approaches. For a layer-by-layer extensible body, the unsteady heat conduction problem is stated. At each step, the height of the computational region increases due to the filling of a new layer of powder. One time step of the calculation is determined by the interval between two consecutive passes of the laser. The temperature distribution found at each step is used as the initial conditions for the calculations at the next step. The temperature field obtained as a result of solving the problem that is implemented in the product in question with a step of 1000 (after applying and melting 1000 layers) is further compared with the solution of the quasi-stationary problem for the finite dimensions product. Using the example of the simple geometry taken, it is shown that a quasi-stationary solution can provide a satisfactory estimate of the macroscopic thermal state of the growing product. [ABSTRACT FROM AUTHOR]

Intensive development of equipment contributes to a significant impact on the high level of competitiveness of new samples, improving technologies, and promise of enshrined ideas as well as resource intensity and time of their implementation. The relevance of the scientific paper lies in the fact that in the process of designing drive systems for guiding aviation equipment, one of the important elements is taking into account the limitations on the power source energy storage. The purpose of the scientific paper is to develop a mathematical model of energy efficiency of mechatronic modules and power sources for prospective mobile objects. An integrated approach is used to study the influence of structures and elements of storage devices on the characteristics of power sources in the interest of finding the ways to increase the energy efficiency of the entire drive system for guiding mechatronic modules of aviation systems in general. It has been determined that in order to reduce the weight-size parameters of the power supply source, the stabilizer in the power section, as a rule, is not set. It has been found out that power and information sections of drive systems differ from each other in terms of the stability of the energy coordinates. And stabilized parameters (potential, current) are necessary only for the information channel. With the help of analytical dependencies, the main parameters of the primary source were evaluated depending on the efficiency of the consumer, efficiency of the stabilizer and efficiency of the secondary power source. A method to study the influence of elements of the energy (power) channel on the output power of the power source the mechatronic modules for prospective aviation mobile objects (autonomous aviation drives, guided missiles, guided parachute systems) is being developed. [ABSTRACT FROM AUTHOR]

Recent NuSTAR and XMM–Newton observations of the molecular cloud around the Arches stellar cluster demonstrate a dramatic change both in morphology and intensity of its non-thermal X-ray emission, similar to that observed in many molecular clouds of the Central Molecular Zone at the Galactic Center. These variations trace the propagation of illuminating fronts, presumably induced by past flaring activities of Sgr A⋆. In this paper, we present results of a long NuSTAR observation of the Arches complex in 2016, taken a year after the previous XMM + NuSTAR observations which revealed a strong decline in the cloud emission. The 2016 NuSTAR observation shows that both the non-thermal continuum emission and the Fe K α 6.4 keV line flux are consistent with the level measured in 2015. No significant variation has been detected in both spectral shape and Fe K α equivalent width EW 6.4 keV, which may be interpreted as the intensity of the Arches non-thermal emission reaching its stationary level. At the same time, the measured 2016 non-thermal flux is not formally in disagreement with the declining trend observed in 2007–2015. Thus, we cannot assess whether the non-thermal emission has reached a stationary level in 2016, and new observations, separated by a longer time period, are needed to draw stringent conclusions. Detailed spectral analysis of three bright clumps of the Arches molecular cloud performed for the first time showed different EW 6.4 keV and absorption. This is a strong hint that the X-ray emission from the molecular cloud is a mix of two components with different origins. [ABSTRACT FROM AUTHOR]

In this paper, we present the results of investigations of degradation processes that occur in the structure promising high-temperature anti-oxidizing of heat-resistant coating of the Si–TiSi2–MoSi2–B–Y system in hypersonic flows of air plasma. The coating is designed to protect a wide range of heat-resistant materials (carbon–carbon and carbon–ceramic composites, coal–graphite materials, alloys based on Nb, Mo, W, etc.). It is found that the coating operating capacity at surface temperatures T w ≤ 1820–1830∘C is provided by the structural-phase state of its microcomposite main layer and formation on the coating surface of a heterogeneous passivating protective film. It is based on borosilicate glass reinforced by rutile microneedles. The mechanism of coating destruction at T w ≥ 1850–1860∘C is erosion loss of oxide film as well as generation and growth of gas-filled cavities at the "coating main layer–oxide film" interface. As the pressure of saturated vapor of gaseous oxidation products (SiO, CO, MoO3 and B2O3) exceeds that of the ambient, the oxide film integrity is disrupted and oxidation process becomes active. The rates of erosion loss and sublimation grow as operating temperature increases and ambient pressure decreases. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the LTB4R/LTB4R2 genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high LTB4R/LTB4R2 expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the LTB4R and LTB4R2 genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = −0.4, p = 2.6 × 10−6; R = −0.21, p = 0.015) and cg21886367 (R = −0.45, p = 7.3 × 10−8; R = −0.24, p = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan–Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated LTB4R. To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated LTB4R/LTB4R2 genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating LTB4R/LTB4R2 hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents. [ABSTRACT FROM AUTHOR]

Zeolites are a special class of inorganic compounds which potentially possess an infinite variety of different structures that are energetically very close to each other. Although the databases of hypothetical zeolite frameworks, which are thermodynamically close to the ground state, contain hundreds of thousands of entries, the number of experimentally obtained frameworks (currently 235) is essentially smaller. We discuss kinetic factors, which should be taken into account along with the thermodynamic ones to explain such great inconsistency and predict more thoroughly new robust zeolite frameworks. In addition to the thermodynamic factors, which determine energetically favorable structures, we consider structural parameters that provide the easiest ways of the structure assemblage. Exploring the existing zeolites, we derive geometrical and topological criteria that should be obeyed when the framework is being formed in the reaction gel. Resting upon these criteria, we extract from the databases of hypothetical zeolite frameworks those frameworks which are the most prospective for synthesis. We discuss also the problem of the purposeful sampling of proper organic structure directing agents and propose a list of them for a target synthesis of the selected hypothetical frameworks. [ABSTRACT FROM AUTHOR]

The plate theory of Nth order is constructed on the background of the Lagrangian variational formalism of analytical dynamics of continuum systems and the dimensional reduction approach of I. N. Vekua - A. A. Amosov. The plate model is defined within the configuration space, the set of field variables, and the Lagrangian density. The field variables are determined by the coefficients of the biorthogonal expansion of the spatial displacement vector field with respect to the dimensionless normal coordinate. The dynamic equations are derived as Lagrange equations of the second kind of the two-dimensional continuum system. The dynamics of the plane elastic layer is considered as an example, the normal wave propagation is described on the basis of refined plate theories of various orders, and the convergence of approximate solutions to the exact solution of the three-dimensional elastodynamics problem is analyzed for different wavenumbers. [ABSTRACT FROM AUTHOR]

On the basis of mathematic simulation, the problem of optimizing the energy storage and the massdimensional parameters of the mechatronic modules of aviation equipment is solved by synthesizing the structure and analyzing the characteristics of various power supplies, a generalized model of the power supply source developed for various power supply sources of the drive control systems is given, a theoretical review of the currently used chemical current sources is carried out, the comparison of sets of external characteristics of capacitive and pneumatic storage media with a set of external characteristics of the chemical current source. The generalized model of the aircraft power supply source, described in the article, can be used in the design of highly efficient mechatronic modules of control systems for autonomous mobile objects of a new generation. [ABSTRACT FROM AUTHOR]

An analytic solution of a Stefan-type problem with one non-stationary moving boundary of phase transformations simulating linear heat transfer in an inhomogeneous medium is considered. In simulating the heat and mass transfer process, the generalized heat equation is used, taking into account the finite rate of heat distribution Cq . This formulation of the problem adequately describes the thermal state of the materials during their high-temperature heating, where the pressure is taken into account because of the low rate of filtration of the pyrolysis gases. It is assumed that the braking pressure should exceed the ambient pressure by the hydraulic resistance of the porous residue. Comparison of numerical and analytical solutions is performed, both. [ABSTRACT FROM AUTHOR]

The lichen biota of the Zeysky Nature Reserve (southern Russian Far East) was studied in the course of geobotanical expedition. In total 36 species of lichens and one lichenicolous fungus are reported for the first time for the reserve. Among them 19 are new to the Amur Region. Parmelia asiatica is reported for the first time for the southern Russian Far East, Cladonia norvegica - for the Asian part of Russia, Tuckermannopsis gilva - for Russia, Melanohalea laciniatula - for Asia. Four species are included in the Red Data Book of Russian Federation. [ABSTRACT FROM AUTHOR]

The lichen biota of the Ragusha River (protected area in Leningrad Region) is studied. In total 221 species (211 lichenized, 5 lichenicolous and 5 saprobic fungi) are listed. Lecanora perpruinosa is new to North-Western European Russia. Lathagrium fuscovirens, Pronectria erythrinella, Protoblastenia rupestris, Thelidium minutulum, T. zwackhii and Tremella hypogymniae are reported for the first time for Leningrad Region, and Ochrolechia bahusiensis for Eastern Leningrad Region. The most noteworthy part of lichen biota is the complex of 21 calcicolous lichens. Eleven of them are known in the region only from the Ragusha River valley. [ABSTRACT FROM AUTHOR]

Background Dysregulation of methylation of lysine 36 on histone H3 (H3K36) have been implicated in a variety of diseases including cancers. ASH1L and SETD2 are two enzymes among others that catalyze H3K36 methylation. H3K4 methylation has also been reported for ASH1L. Methods Radioactivity-based enzyme assays, Western and immunoblotting using specific antibodies and molecular modeling were used to characterize substrate specificity of ASH1L and SETD2. Results Here we report on the assay development and kinetic characterization of ASH1L and SETD2 and their substrate specificities in vitro . Both enzymes were active with recombinant nucleosome as substrate. However, SETD2 but not ASH1L methylated histone peptides as well indicating that the interaction of the basic post-SET extension with substrate may not be critical for SETD2 activity. Both enzymes were not active with nucleosome containing a H3K36A mutation indicating their specificity for H3K36. Analyzing the methylation state of the products of ASH1L and SETD2 reactions also confirmed that both enzymes mono- and dimethylate H3K36 and are inactive with H3K4 as substrate, and that only SETD2 is able to trimethylate H3K36 in vitro . Conclusions We determined the kinetic parameters for ASH1L and SETD2 activity enabling screening for inhibitors that can be used to further investigate the roles of these two proteins in health and disease. Both ASH1L and SETD2 are H3K36 specific methyltransferases but only SETD2 can trimethylate this mark. The basic post-SET extension is critical for ASH1L but not SETD2 activity. General significance We provide full kinetic characterization of ASH1L and SETD2 activity. [ABSTRACT FROM AUTHOR]

The haloacid dehalogenase (HAD)-like enzymes comprise a large superfamily of phosphohydrolases present in all organisms. The Saccharomyces cerevisiae genome encodes at least 19 soluble HADs, including 10 uncharacterized proteins. Here, we biochemically characterized 13 yeast phosphatases from the HAD superfamily, which includes both specific and promiscuous enzymes active against various phosphorylated metabolites and peptides with several HADs implicated in detoxification of phosphorylated compounds and pseudouridine. The crystal structures of four yeast HADs provided insight into their active sites, whereas the structure of the YKR070W dimer in complex with substrate revealed a composite substrate-binding site. Although the S. cerevisiae and Escherichia coli HADs share low sequence similarities, the comparison of their substrate profiles revealed seven phosphatases with common preferred substrates. The cluster of secondary substrates supporting significant activity of both S. cerevisiae and E. coli HADs includes 28 common metabolites that appear to represent the pool of potential activities for the evolution of novel HAD phosphatases. Evolution of novel substrate specificities of HAD phosphatases shows no strict correlation with sequence divergence. Thus, evolution of the HAD superfamily combines the conservation of the overall substrate pool and the substrate profiles of some enzymes with remarkable biochemical and structural flexibility of other superfamily members. [ABSTRACT FROM AUTHOR]

Abstract: Canine generalized demodicosis (CGD) is a skin disease with distinct breed predispositions. Secondary bacterial infections are common. Dogs typically receive miticidal therapy in combination with antibacterial treatment. Whether antibiotics influence the duration of acaricidal therapy is unknown at the moment. There is also debate over how common short-tailed Demodex mites occur in demodicosis. This study evaluated the influence of systemic antibiotics on the course of CGD, the occurrence of short-tailed Demodex mites in demodectic dogs and the influence of furunculosis on treatment outcome. Breed predispositions for CGD in Moscow were identified. Fifty-eight dogs were randomly distributed in two groups. Both were treated with ivermectin 600mcg/kg q24h orally and benzoyl peroxide shampoo weekly. The dogs in one group (AB) were additionally treated with systemic antibiotics for at least 1 month, dogs in the other group (NAB) were not. Monthly examinations, skin scrapings and impression smears were performed. Prior to the study there was no difference in clinical severity, presence of pyoderma and mite numbers between groups. There was no significant difference in duration until first negative skin scrapings and resolution of bacterial infection. In dogs with furunculosis the number of the mites was significantly higher than in dogs without furunculosis but the duration until microscopic remission albeit longer, was not significantly different. Short-tailed Demodex mites were found in 25% of the cases. Pugs and English Bulldogs were predisposed. Based on these results, systemic antibiotics may not impact as much as previously thought on the actual success of CGD treatment. [Copyright &y& Elsevier]

It is well known that all real automatic control systems (ACS) are significantly nonlinear systems. Along with this, in engineering analysis the simplifications of their mathematic description, that is, linearization, are inevitable. These simplifications naturally introduce errors into engineering calculations. For the most complicated calculation of stability conditions, these errors can be very significant, since they lead to not only incorrect forecast of the ACS condition but also to the operating inability of the designed ACS. Most often, engineers simplify nonlinear structures in their calculations. In other words, they linearize these structures according to one of the numerous approaches which have been developed over 100 years. Calculation methods for linear ACS, in particular the Nyquist criterion, can be applied to the already linearized structure for the calculation of ACS stability condition. In this article, the authors suppose that for electromechanical and power ACS it would be more effective to widely use the absolute stability criterions or hyperstability which were developed when solving the "Aizerman problem" by V.M. Popov in the 1960s of the 20th century. This solution is not used as widely as the Nyquist criterion despite its outstanding qualities. In this article, the assumption was made that it is effective to apply the stability criterion of nonlinear ACS for the linearized models of nonlinear systems. Otherwise speaking, it is effective to use the criterion of V.M. Popov and its interpretation according to the logarithmic frequency characteristics of the ACS proposed earlier by the authors of the article. The authors provide simple and illustrative examples and give the results of the simulation. [ABSTRACT FROM AUTHOR]

Twelve Galago senegalensis from the Moscow Zoo were presented with papular to nodular (2-11 mm) lesions on the pinnae, containing a white, waxy material. Microscopic examination revealed large numbers of mites consistent with the morphology of Demodex spp. mites. Nine animals were treated with ivermectin, 600 μg/kg/day topically, orally or subcutaneously for 3-10 months, while one remained untreated. All the treated animals achieved clinical remission. The control animal was still affected and died 11 months later due to pneumonia and possible eosinophilic leukaemia. No adverse effects were noted in any animals during the treatment. No animal relapsed in the 13-19 months follow-up period. To the authors' knowledge, this is the first report of demodicosis in G. senegalensis. The use of ivermectin in G. senegalensis was safe, although its effectiveness in the treatment of demodicosis needs further investigation. [ABSTRACT FROM AUTHOR]

Eight species of lichen-forming, eight lichenicolous and three non-lichenized fungi are reported from the Leningrad Region. Arthonia caerulescens, A. ligniaria, Hawksworthiana peltigericola, Micarea pycnidiophora and Trichonectria rubefaciens are new to Russia; Micarea lutulata, Protoparmelia oleagina and Stictis radiata are new to the North-Western European Russia; Lichenoconium lecanorae, Phaeocalicium populneum, Phaeosporobolus usneae, Ramboldia cinnabarina, Stictis brunnescens and Strigula stigmatella are new to the Leningrad Region. Most noteworthy records are briefly discussed. [ABSTRACT FROM AUTHOR]

Fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis and photosynthetic CO2 fixation, catalyzes the hydrolysis of fructose 1,6-bisphosphate (FBP) to produce fructose 6-phosphate, an important precursor in various biosynthetic pathways. All known FBPases are metal-dependent enzymes, which are classified into five different classes based on their amino acid sequences. Eukaryotes are known to contain only the type-I FBPases, whereas all five types exist in various combinations in prokaryotes. Here we demonstrate that the uncharacterized protein YK23 from Saccharomyces cerevisiae efficiently hydrolyzes FBP in a metal-independent reaction. YK23 is a member of the histidine phosphatase (phosphoglyc-eromutase) superfamily with homologues found in all organisms. The crystal structure of the YK23 apo-form was solved at 1.75-Å resolution and revealed the core domain with the α/β/ α-fold covered by two small cap domains. Two liganded structures of this protein show the presence of two phosphate molecules (an inhibitor) or FBP (a substrate) bound to the active site. FBP is bound in its linear, open conformation with the cleavable C1-phosphate positioned deep in the active site. Alanine replacement mutagenesis of YK23 identified six conserved residues absolutely required for activity and suggested that His13 and Glu99 are the primary catalytic residues. Thus, YK23 represents the first family of metal-independent FBPases and a second FBPase family in eukaryotes. [ABSTRACT FROM AUTHOR]

Background: Canine demodicosis is a common disease in small animal practice. Although a number of studies evaluating treatment efficacy for canine demodicosis have used clinical scoring systems, none have been validated. Objectives: This study evaluated the validity, reliability, reproducibility and sensitivity to change of a clinical scoring system for canine demodicosis. Methods and materials: Fifty‐eight dogs with generalised demodicosis were evaluated using a clinical scoring system that assessed erythema, comedones/ papules/pustules, follicular casts/scales/crusts and alopecia, rated from none to mild, moderate and severe in 36 body locations. Two evaluators scored lesions at monthly consecutive visits during treatment. Mites were counted to a maximum of 50 in four deep skin scrapings. With >50 mites, the approximate mite number was calculated with the help of a grid drawn onto the slide before placing the scraped material onto it. Results: A Pearson correlation coefficient showed a high interobserver reliability (r = 0.97) between two different clinicians evaluating the same dog. The Wilcoxon signed rank test showed good sensitivity to change with a reduction of clinical scores with each of the first six evaluations (P < 0.0001). A linear mixed model also showed a clear reduction in mite counts (P < 0.001) and clinical scores (P < 0.0001) from the first evaluation with time. Conclusion and clinical relevance: The clinical scoring system for canine demodicosis evaluated in this study showed a good sensitivity to change and interobserver reliability, and can be used in studies evaluating canine demodicosis. [ABSTRACT FROM AUTHOR]

The paper deals with lichen flora of Vepssky Forest Protected Area situated in the Eastern Leningrad Region (northwestern Russia). In total 183 species of lichens and allied fungi are reported. Eight species of lichens — Biatora flavopunctata, Bryoria fremontii, Chaenotheca cf. gracilenta, Chaenotheca laevigata, Lecidea enclitica, Lepraria lobificans, Multiclavula vernalis, Pyrrhospora elabens and three species of lichenicolous fungi — Chaenothecopsis nigra, Chaenothecopsis viridi-alba, Dactylospora deminuta — are reported here for the first time in the Leningrad Region. Chaenotheca sphaerocephala and Lecanora cf. ramulicola are new for Russia. A total of 38 species are indicators of habitats with long ecological continuity. [ABSTRACT FROM AUTHOR]

Background: Loss of BIN1 tumor suppressor expression is abundant in human cancer and its frequency exceeds that of genetic alterations, suggesting the role of epigenetic regulators (DNA methylation). BIN1 re-expression in the DU145 prostate cancer cell line after 5-aza-2′-deoxycytidine treatment was recently reported but no methylation of the BIN1 promoter CpG island was found in DU145. Methods: Methylation-sensitive arbitrarily-primed PCR was used to detect genomic loci abnormally methylated in breast cancer. BIN1 CpG island fragment was identified among the differentially methylated loci as a result of direct sequencing of the methylation-sensitive arbitrarily-primed PCR product and subsequent BLAST alliance. BIN1 CpG island cancer related methylation in breast and prostate cancers was confirmed by bisulphite sequencing and its methylation frequency was evaluated by methylation sensitive PCR. Loss of heterozygosity analysis of the BIN1 region was performed with two introgenic and one closely adjacent extragenic microsatellite markers.BIN1 expression was evaluated by real-time RTPCR. Results: We have identified a 3′-part of BIN1 promoter CpG island among the genomic loci abnormally methylated in breast cancer. The fragment proved to be methylated in 18/99 (18%) and 4/46 (9%) breast and prostate tumors, correspondingly, as well as in MCF7 and T47D breast cancer cell lines, but was never methylated in normal tissues and lymphocytes as well as in DU145 and LNCaP prostate cancer cell lines. The 5′-part of the CpG island revealed no methylation in all samples tested. BIN1 expression losses were detected in MCF7 and T47D cells and were characteristic of primary breast tumors (10/13; 77%), while loss of heterozygosity was a rare event in tissue samples (2/22 informative cases; 9%) and was ruled out for MCF7. Conclusion: BIN1 promoter CpG island is composed of two parts differing drastically in the methylation patterns in cancer. This appears to be a common feature of cancer related genes and demands further functional significance exploration. Although we have found no evidence of the functional role of such a non-core methylation in BIN1 expression regulation, our data do not altogether rule this possibility out. [ABSTRACT FROM AUTHOR]

Haloacid dehalogenase (HAD)-like hydrolases are a vast super- family of largely uncharacterized enzymes, with a few members shown to possess phosphatase, β-phosphoglucomutase, phosphonatase, and dehalogenase activities. Using a representative set of 80 phosphorylated substrates, we characterized the substrate specificities of 23 soluble HADs encoded in the Escherichia coli genome. We identified small molecule phosphatase activity in 21 HADs and β-phosphoglucomutase activity in one protein. The E. coli HAD phosphatases show high catalytic efficiency and affinity to a wide range of phosphorylated metabolites that are intermediates of various metabolic reactions. Rather than following the classical "one enzyme-one substrate" model, most of the E. coli HADs show remarkably broad and overlapping substrate spectra. At least 12 reactions catalyzed by HADs currently have no EC numbers assigned in Enzyme Nomenclature. Surprisingly, most HADs hydrolyzed small phosphodonors (acetyl phosphate, carbamoyl phosphate, and phosphoramidate), which also serve as substrates for autophosphorylation of the receiver domains of the two-component signal transduction systems. The physiological relevance of the phosphatase activity with the preferred substrate was validated in vivo for one of the HADs, YniC. Many of the secondary activities of HADs might have no immediate physiological function but could comprise a reservoir for evolution of novel phosphatases. [ABSTRACT FROM AUTHOR]

The article presents an interview with Andrei Ovcharov of the IBR, a company analyzing the problems of nuclear power engineering in Russia. He emphasizes that the summit meeting of the Group of Eight in Saint Petersburg will include the problems of nuclear power engineering. He expresses his views on the move of Russian President Vladimir Putin to create centers to enrich uranium and store nuclear waste. He comments on the position of nuclear power engineering in the Russian economy.

The article presents an interview with Eduard Shevardnadze, a multifaceted political figure of the Soviet Union and the Commonwealth of Independent States. When asked about Georgian politics and its domestic problems, he chose not to comment on it but instead promoted his new book that would present all the answers he should have answered. His book is both a memoir and a presentation of the past, and current trends of Georgian politics.

Analyzes the motive of the strategic partnership between the Russian Federation and the European Union. Proposal for creating an open and integrated market that will give producers favorable chances for cooperation, provide investment protection for investors and guarantee consumers high standards and quality of goods; Impact of the lack of a strict ecological legislation on the ecological situation in cities; Implications of the collapse of the Euroconstitution referendum in France for the Russian foreign policy.

Discusses the reconciliation of the U.S. and Europe. Impact of the decision of the administration of U.S. President George W. Bush to carry out a military intervention in Iraq on its relation with Europe; Difference of the views of the countries on world order principles; Basis of the agenda of the visit of Bush in Europe.

Abstract: In all sequenced genomes, a large fraction of predicted genes encodes proteins of unknown biochemical function and up to 15% of the genes with “known” function are mis-annotated. Several global approaches are routinely employed to predict function, including sophisticated sequence analysis, gene expression, protein interaction, and protein structure. In the first coupling of genomics and enzymology, Phizicky and colleagues undertook a screen for specific enzymes using large pools of partially purified proteins and specific enzymatic assays. Here we present an overview of the further developments of this approach, which involve the use of general enzymatic assays to screen individually purified proteins for enzymatic activity. The assays have relaxed substrate specificity and are designed to identify the subclass or sub-subclasses of enzymes (phosphatase, phosphodiesterase/nuclease, protease, esterase, dehydrogenase, and oxidase) to which the unknown protein belongs. Further biochemical characterization of proteins can be facilitated by the application of secondary screens with natural substrates (substrate profiling). We demonstrate here the feasibility and merits of this approach for hydrolases and oxidoreductases, two very broad and important classes of enzymes. Application of general enzymatic screens and substrate profiling can greatly speed up the identification of biochemical function of unknown proteins and the experimental verification of functional predictions produced by other functional genomics approaches. [Copyright &y& Elsevier]

To find proteins with nucleotidase activity in Escherichia coli, purified unknown proteins were screened for the presence of phosphatase activity using the general phosphatase substrate p-nitrophenyl phosphate. Proteins exhibiting catalytic activity were then assayed for nucleotidase activity against various nucleotides. These screens identified the presence of nucleotidase activity in three uncharacterized E. coli proteins, SurE, YfbR, and YjjG, that belong to different enzyme super-families: SurE-like family, HD domain family (YfbR), and haloacid dehalogenase (HAD)-like superfamily (YjjG). The phosphatase activity of these proteins had a neutral pH optimum (pH 7.0–8.0) and was strictly dependent on the presence of divalent metal cations (SurE: Mn2+ > Co2+ > Ni2+ > Mg2+; YfbR: Co2+ > Mn2+ > Cu2+; YjjG: Mg2+ > Mn2+ > Co2+). Further biochemical characterization of SurE revealed that it has a broad substrate specificity and can dephosphorylate various ribo- and deoxyribonucleoside 5′-monophosphates and ribonucleoside 3′-monophosphates with highest affinity to 3′-AMP. SurE also hydrolyzed polyphosphate (ex- opolyphosphatase activity) with the preference for short-chain-length substrates (P20–25). YfbR was strictly specific to deoxyribonucleoside 5′-monophosphates, whereas YjjG showed narrow specificity to 5′-dTMP, 5′- dUMP, and 5′-UMP. The three enzymes also exhibited different sensitivities to inhibition by various nucleoside di- and triphosphates: YfbR was equally sensitive to both di- and triphosphates, SurE was inhibited only by triphosphates, and YjjG was insensitive to these effectors. The differences in their sensitivities to nucleotides and their varied substrate specificities suggest that these enzymes play unique functions in the intracellular nucleotide metabolism in E. coli. [ABSTRACT FROM AUTHOR]

Interviews Fareed Zakaria, editor of the periodical "Newsweek International," on U.S. international relations. Chances for co-existence between the U.S. and the Muslim East after the 2003 war in Iraq; Sufficiency of the leadership against terrorism asserted by the U.S.; Alleged establishment of world hegemony by the country.

Discusses the relationship of the North Atlantic Treaty Organization (NATO) with Russia. List of countries that joined NATO in April 2004; Percentage of Russians who are convinced that the enlargement of NATO threatens Russia's national interests; Aim of the antiterrorist operations of NATO.

Discusses the role of Europe in world politics in the contemporary world. Geopolitical aims and intentions of the U.S.; International relations between Europe and the U.S.; Three possible options for a European identity in foreign policy issues.

Argues that the present-day world is not a world under globalization and that the only real problem is intercivilizational conflict. Basic values of the Western society; Examination of the dimensions of globalization; Possible scenarios of the development of the future intercivilizational conflict.

Feline proliferative and necrotising otitis externa (PNOE) is a rare immune‐mediated condition, usually self‐limiting or responsive to immunosuppressants such as topical tacrolimus. This case report describes two cats with refractory PNOE that responded successfully to oclacitinib. One cat also had middle ear involvement and the other cat had extra‐auricular dermatitis. [ABSTRACT FROM AUTHOR]

In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers. Being dynamic and reversible, epigenetic modifications could become targets for a novel option for therapy. Therefore, in this review, we are focusing on histone modifications and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application. [ABSTRACT FROM AUTHOR]

The International Gamma-Ray Astrophysics Laboratory (INTEGRAL), launched in 2002, continues its successful work in observing the sky at energies E > 20 keV. The legacy of the mission already includes a large number of discovered or previously poorly studied hard X-ray sources. The growing INTEGRAL archive allows one to conduct an all-sky survey including a number of deep extragalactic fields and the deepest ever hard X-ray survey of the Galaxy. Taking advantage of the data gathered over 17 yr with the IBIS coded-mask telescope of INTEGRAL , we conducted survey of hard X-ray sources, providing flux information from 17 to 290 keV. The catalogue includes 929 objects, 890 of which exceed a detection threshold of 4.5σ and the rest are detected at 4.0σ–4.5σ and belong to known catalogued hard X-ray sources. Among the identified sources of known or suspected nature, 376 are associated with the Galaxy and Magellanic clouds, including 145 low-mass and 115 high-mass X-ray binaries, 79 cataclysmic variables, and 37 of other types; and 440 are extragalactic, including 429 active galactic nuclei (AGNs), 2 ultra-luminous sources, 1 supernova (AT2018cow), and 8 galaxy clusters. 113 sources remain unclassified. 46 objects are detected in the hard X-ray band for the first time. The Log N -Log S distribution of 356 non-blazar AGNs is measured down to a flux of 2 × 10−12 erg s−1 cm−2 and can be described by a power law with a slope of 1.44 ± 0.09 and normalization 8 × 10−3 deg−2 at 10−11 erg s−1 cm−2. The Log N -Log S distribution of unclassified sources indicates that the majority of them are of extragalactic origin. [ABSTRACT FROM AUTHOR]

Hibernating mammals have annual cycles with strict timing of all processes including reproduction, yet female reproductive physiology is only poorly studied in such species. We investigated the estrous cycle in yellow ground squirrels (Spermophilus fulvus), which hibernate up to 9 months. Using vaginal cytology and serum progesterone and estradiol profiles, we identified proestrus, estrus, metestrus, and anestrus in the cycle. As in other rodents, predominance of cornified cells marked estrus, and an increase in the leukocyte number reflected metestrus. The only estrus in a year started, and then, pregnancy occurred mostly within 3 days after spring emergence. In one female, we noticed a copulatory plug for the first time for this species. The progesterone level increased from proestrus/estrus to pregnancy and decreased in the postlactation period. Estradiol concentration did not change significantly throughout the estrous cycle but varied among females and was consistently high in some of them. The hormone levels did not vary with female age despite smaller body size in yearling females than in older ones. During postlactation, progesterone concentration diminished toward hibernation, and we could not detect signs of prehibernation activation of the female reproductive system. Probably, gonadal preparation in S. fulvus females proceeds at periodic arousals during hibernation. Our data showed fast transitions between phases of the female estrous cycle and early maturation of juvenile females, consistently with the hypothesis of the fast life-history strategy of S. fulvus. [ABSTRACT FROM AUTHOR]