Cytokine Gene Polymorphisms in Chronic Adenoiditis

The aim of our research was to study the multiphase response in a system of pro-inflammatory and anti-inflammatory cytokines due to the additive contribution of homozygous and heterozygous genotypes for the polymorphic allelic variants of the interleukin-1β (IL-1β) and interleukin-4 (IL-4) genes in patients with chronic adenoiditis (CA). Materials and Methods: The study included 388 children with CA. Associations between the IL1B gene (rs1143634) (C+3954T) SNP and the IL-4 gene (rs2243250) (C-589T) SNP and the clinical manifestations and clinical outcome of CA were investigated. Genotyping for the studied SNPs was performed using real-time PCR. The study of genotype-associated cytokine production in accordance with the level of concentration of IL-1β, IL-4 in blood serum with the method of solidphase EIA using horseradish peroxidase as an indicating enzyme was carried out. Results: The presence of homozygous or heterozygous genotypes of the studied SNPs of the IL-1β and IL-4 genes was characterized with genetically determined cytokine-production forming the phenotypical polymorphism. The conducted research into congenital immunity factors with an assessment of genetically determined cytokine production has revealed 5 options of the cytokine response and their corresponding frequencies. We extrapolated the results on clinical and functional outcomes of chronic adenoiditis, which allowed us to identify non-randomness in the nature of chronic adenoiditis as a multifactorial disease. Conclusion: The obtained data are evidence of the phenotypic-genetic heterogeneity of CA

Electronic transport and magnetism in the alternating stack of metallic and highly frustrated magnetic layers in Co1/3_{1/3}NbS2_2

Co$_{1/3}$NbS$_2$ is the only magnetically intercalated layered transition metal dichalcogenide (TMD) suggested to experience the complete suppression of magnetic order under pressure. From elastic neutron scattering we report the direct evidence for the reduction of the antiferromagnetic ordering temperature under pressure, up to complete suppression of magnetic order around 1.7 GPa. The static and ac magnetic susceptibility measurements reveal strong frustration in the magnetic subsystem, and spin canting responsible for the appearance of ferromagnetic (FM) component in dominantly antiferromagnetic (AF) ordered state. The electric transport in directions perpendicular and parallel to layers is explored for the first time in magnetically intercalated TMDs, in the wide temperature and pressure ranges. We show that electric transport reacts differently to magnetic ordering in directions along and perpendicular to layers, with the in-plane conductivity increasing, and the out-of-plane conductivity decreasing in the ordered state. At pressures above 3 GPa, we identify the appearance of the Kondo scattering regime. We use ab-initio calculations to explore the electronic structure in magnetically ordered state, the nature of magnetic interactions, and the mechanism responsible for the changes observed under pressure. The mechanisms of suppression of magnetic order under pressure are scrutinized in the light of these experimental and theoretical findings. We conclude that magnetic couplings beyond nearest-neighbors determine the nature of magnetic ordering. The suppression of ordering under pressure is ascribed to the pressure-induced shift in balance between super-exchange and Ruderman-Kittel-Kasuya-Yosida (RKKY) magnetic couplings, leading to amplified magnetic frustration.Comment: 34 pages, 17 figure

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Improving the efficiency of the technology and organization of the longwall face move during the intensive flat-lying coal seams mining at the Kuzbass mines

The reasons for the lag of the indicators of the leading Russian coal mines engaged in the longwall mining of the flat-lying coal seams from similar foreign mines are considered. The analysis of the efficiency of the longwall face move operations at the JSC SUEK-Kuzbass mines was carried out. A significant excess of the planned deadlines for the longwall face move during the thick flat-lying seams mining, the reasons for the low efficiency of disassembling operations and the main directions for improving the technology of disassembling operations are revealed. The directions of ensuring the operational condition of the recovery room formed by the longwall face are considered. The recommended scheme of converged coal seams mining and a three-dimensional model of a rock mass to justify its parameters are presented. Numerical studies using the finite element method are performed. The results of modeling the stress-strain state of a rock mass in the vicinity of a recovery room formed under conditions of increased stresses from the boundary part of a previously mined overlying seam are shown. The main factors determining the possibility of ensuring the operational condition of the recovery rooms are established. It is shown that it is necessary to take into account the influence of the increased stresses zone when choosing timbering standards and organizing disassembling operations at a interbed thickness of 60 m or less. A sufficient distance from the gob of above- or undermined seams was determined to ensure the operational condition of the recovery room of 50 m, for the set-up room – 30 m. Recommendations are given for improving technology and organization of the longwall face move operations at the mines applied longwall mining of flat-lying coal seams with the formation of a recovery room by the longwall face

Secure simultaneous bit extraction from Koblitz curves

\u3cp\u3eSecure pseudo-random number generators (PRNGs) have a lot of important applications in cryptography. In this paper, we analyze a new PRNG related to the elliptic curve power generator. The new PRNG has many desirable randomness properties such as long period, uniform distribution, etc. In particular, the proposed PRNG is provably secure under the l-strong Diffie–Hellman assumptions. An important feature of our PRNG is that many bits can be simultaneously output without significantly affecting its security. For instance, at 150-bit security, more than 100 bits can be output at each iteration, with a statistical distance from a uniform sequence less than 1 / 2 \u3csup\u3e150\u3c/sup\u3e. Our experimental results show that the new PRNG provides a secure and flexible solution for high security applications. Hence, our work is another step towards the construction of provably secure PRNGs in practice. \u3c/p\u3

Determining the local low-energy excitations in the Kondo semimetal CeRu4Sn6 using resonant inelastic x-ray scattering

We have investigated the local low-energy excitations in CeRu4Sn6, a material discussed recently in the framework of strongly correlated Weyl semimetals, by means of Ce M-5 resonant inelastic x-ray scattering (RIXS). The availability of both F-2(5/2) and F-2(7/2) excitations of the Ce 4f(1) configuration in the spectra allows for the determination of the crystal-electric field (CEF) parameters that explain quantitatively the high-temperature anisotropy of the magnetic susceptibility. The absence of an azimuthal dependence in the spectra indicates that all CEF states are close to being rotational symmetric. We show further that the non-negligible impact of the (sic)(6)(0) parameter on the ground state of CeRu4Sn6 leads to a reduction of the magnetic moment mu(c) due to multiplet intermixing. This improves the agreement between CEF calculations and the experimentally determined magnetic susceptibility considerably at low temperatures. Deviations that persist at low temperatures for fields within the tetragonal plane are attributed to the Kondo interaction between 4f and conduction electrons. The RIXS results are consistent with inelastic neutron scattering data and are compared to the predictions from ab initio based electronic structure calculations

Pristine and antibiotic-loaded nanosheets/nanoneedles-based boron nitride films as a promising platform to suppress bacterial and fungal infections

In recent years, bacteria inactivation during their direct physical contact withsurface nanotopography has become one of the promising strategies for fighting infection. Contact-killing ability has been reported for several nanostructured surfaces, e.g. black silicon, carbon nanotubes, zinc oxide nanorods, and copper oxide nanosheets. Herein, we demonstrate that Gram-negative antibiotic-resistant Escherichia coli (E. coli) bacteria are killed as a result of their physical destruction while contacting nanostructured h-BN surfaces. BN films, made ofspherical nanoparticles formed by numerous nanosheets and nanoneedles with a thickness 99 % inactivation of colony forming units after 24 h, same as gentamicin-loaded (150 µg/cm2) BN sample. The BN films loaded with a mixture of gentamicin (150 and 300 µg/cm2) and amphotericin B (100 µg/cm2) effectively inhibit the growth of E. coli K-261 and Neurospora crassa strains. During immersion in the normal saline solution, the BN film generates reactiveoxygen species (ROS), which can lead to accelerated oxidative stress at the site of physical cell damage. The obtained results are valuable for further development of nanostructured surfaces having contact killing, ROS and biocide release abilities