Quantum analogue of the spin-flop transition for a spin pair

Quantum (step-like) magnetization curves are studies for a spin pair with antiferromagnetic coupling in the presence of a magnetic field parallel to the easy axis of the magnetic anisotropy. The consideration is done both analytically and numerically for a wide range of the anisotropy constants and spins up to $S \gtrsim 100$. Depending on the origin of the anisotropy (exchange or single-ion), the magnetization curve can demonstrate the jumps more than unity and the concentration of the unit jumps in a narrow range of the field. We also point the region of the problem parameters, where the behavior is quasiclassical for $S = 5$, and where system is substantially quantum in the limit $S \to \infty$.Comment: 5 pages, 5 figure

Development of a High-Throughput Assay for Identifying Inhibitors of TBK1 and IKKε

IKKε and TBK1 are noncanonical IKK family members which regulate inflammatory signaling pathways and also play important roles in oncogenesis. However, few inhibitors of these kinases have been identified. While the substrate specificity of IKKε has recently been described, the substrate specificity of TBK1 is unknown, hindering the development of high-throughput screening technologies for inhibitor identification. Here, we describe the optimal substrate phosphorylation motif for TBK1, and show that it is identical to the phosphorylation motif previously described for IKKε. This information enabled the design of an optimal TBK1/IKKε substrate peptide amenable to high-throughput screening and we assayed a 6,006 compound library that included 4,727 kinase-focused compounds to discover in vitro inhibitors of TBK1 and IKKε. 227 compounds in this library inhibited TBK1 at a concentration of 10 µM, while 57 compounds inhibited IKKε. Together, these data describe a new high-throughput screening assay which will facilitate the discovery of small molecule TBK1/IKKε inhibitors possessing therapeutic potential for both inflammatory diseases and cancer

High-Throughput Screening for RecA Inhibitors Using a Transcreener Adenosine 5′- O -Diphosphate Assay

The activities of the bacterial RecA protein are involved in the de novo development and transmission of antibiotic resistance genes, thus allowing bacteria to overcome the metabolic stress induced by antibacterial agents. RecA is ubiquitous and highly conserved among bacteria, but has only distant homologs in human cells. Together, this evidence points to RecA as a novel and attractive antibacterial drug target. All known RecA functions require the formation of a complex formed by multiple adenosine 5′-O-triphosphate (ATP)-bound RecA monomers on single-stranded DNA. In this complex, RecA hydrolyzes ATP. Although several methods for assessing RecA's ATPase activity have been reported, these assay conditions included relatively high concentrations of enzyme and ATP and thereby restricted the RecA conformational state. Herein, we describe the validation of commercial reagents (Transcreener® adenosine 5′-O-diphosphate [ADP]2 fluorescence polarization assay) for the high-throughput measurement of RecA's ATPase activity with lower concentrations of ATP and RecA. Under optimized conditions, ADP detection by the Transcreener reagent provided robust and reproducible activity data (Z′=0.92). Using the Transcreener assay, we screened 113,477 small molecules against purified RecA protein. In total, 177 small molecules were identified as confirmed hits, of which 79 were characterized by IC50 values ≤10 μM and 35 were active in bioassays with live bacteria. This set of compounds comprises previously unidentified scaffolds for RecA inhibition and represents tractable hit structures for efforts aimed at tuning RecA inhibitory activity in both biochemical and bacteriological assays

Innovation Performance and its Influence on Enterprise Economic Efficiency in the Market

Innovations are means of competition. A success in how an enterprise uses the innovation processes directly depends on its competitive ability and profitability level. Innovation performance is a level of using innovations. Under a competitive struggle in the market, progress in science and technology holds a specific place. Innovations define the economic success of an organization. It is not simple to have only a desire to increase the performance results, it is necessary to have a factor for organization survival, competitive ability and economic growth prospects preservation throughout the modern innovation world. The experience of the most developed countries shows that the one, whose activity is mainly based on using the innovation processes, becomes a winner in a fight for his client and the main purpose of organizations' strategic plan is to develop either a new product or services. The innovation performance of an enterprise can become one of the main factors for organizing the competitive strategic prospects of an enterprise, preserving and increasing its positions in the market. The topicality of the theme is very high, as introducing innovations in the activity of an enterprise and its competitive ability level in the market depend on the level of an organization's innovation performance. Keywords: innovation, innovation performance JEL Classifications: O14, O31, O32, O3

Alternative approach to electromagnetic field quantization in nonlinear and inhomogeneous media

A simple approach is proposed for the quantization of the electromagnetic field in nonlinear and inhomogeneous media. Given the dielectric function and nonlinear susceptibilities, the Hamiltonian of the electromagnetic field is determined completely by this quantization method. From Heisenberg's equations we derive Maxwell's equations for the field operators. When the nonlinearity goes to zero, this quantization method returns to the generalized canonical quantization procedure for linear inhomogeneous media [Phys. Rev. A, 43, 467, 1991]. The explicit Hamiltonians for the second-order and third-order nonlinear quasi-steady-state processes are obtained based on this quantization procedure.Comment: Corrections in references and introductio

Identification of Non-Peptide Malignant Brain Tumor (MBT) Repeat Antagonists by Virtual Screening of Commercially Available Compounds

The Malignant Brain Tumor (MBT) repeat is an important epigenetic-code “reader” and is functionally associated with differentiation, gene silencing and tumor suppression1–3. Small molecule probes of MBT domains should enable a systematic study of MBT-containing proteins, and potentially reveal novel druggable targets. We designed and applied a virtual screening strategy, which identified potential MBT antagonists in a large database of commercially available compounds. A small set of virtual hits was purchased and submitted to experimental testing. Nineteen of the purchased compounds showed a specific dose-dependent protein binding and will provide critical structure-activity information for subsequent lead generation and optimization

New Method of Plague Agent Lipopolysaccharide Obtaining

Put forward are two alternatives of a new method for optimization of conditions of LPS obtaining and purification from Y. pestis strains; as well as for avoiding application of poisonous and hard-to-remove reagents; for simplification and cost-cutting of the technique; and for rationalization of production waste management. This method involves preliminary salt-water extraction of bacteria, for elimination of easy-dissolving substances, with the subsequent fracturing using ultrasound in lysing buffer (0,1 M Tris-HCl, pH 8,0; 10 mmol of EDTA, 1 % Triton X-100). The first alternative for deproteinization of non-purified endotoxin is the commercial preparation of proteinase K (Sigma), the second one - an enzyme complex - proteovibrin, isolated from waste material accumulated in the process of cholera chemical bivalent vaccine production. Apart from this, introduced has been a phase of sample acidification by applying glacial acetic acid up to pH 3,2-3,4 to decontaminate LPS from nucleic acids. These two variations of the method provide for enhancement of LPS preparation quality as compared to prototype method, and for obtainment of plague agent endotoxin that is hardly distinguishable in physical-chemical properties, homogeneity, immunochemical activity and specificity from the antigen, manufactured by means of water-phenol extraction following Westphal O. technique

Properties of Neutral Charmed Mesons in Proton--Nucleus Interactions at 70 GeV

The results of treatment of data obtained in the SERP-E-184experiment "Investigation of mechanisms of the production of charmed particles in proton-nucleus interactions at 70 GeV and their decays" by irradiating the active target of the SVD-2 facility consisting of carbon, silicon, and lead plates, are presented. After separating a signal from the two-particle decay of neutral charmed mesons and estimating the cross section for charm production at a threshold energy {\sigma}(c\v{c})=7.1 \pm 2.4(stat.) \pm 1.4(syst.) \mub/nucleon, some properties of D mesons are investigated. These include the dependence of the cross section on the target mass number (its A dependence); the behavior of the differential cross sections d{\sigma}/dpt2 and d{\sigma}/dxF; and the dependence of the parameter {\alpha} on the kinematical variables xF, pt2, and plab. The experimental results in question are compared with predictions obtained on the basis of the FRITIOF7.02 code.Comment: 9 pages, 9 figures,3 table

Development of a High-Throughput Screening Assay to Identify Inhibitors of the Lipid Kinase PIP5K1C

Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) regulate a variety of cellular processes including signaling through G protein-coupled receptors (GPCRs), endocytosis, exocytosis, and cell migration. These lipid kinases synthesize phosphatidylinositol 4,5-bisphosphate (PIP2) from phosphatidylinositol 4-phosphate [PI(4)P]. Since small molecule inhibitors of these lipid kinases did not exist, molecular and genetic approaches were predominantly used to study PIP5K1 regulation of these cellular processes. Moreover, standard radioisotope-based lipid kinase assays cannot be easily adapted for high-throughput screening. Here, we report a novel high-throughput microfluidic mobility shift assay to identify inhibitors of PIP5K1C. This assay utilizes fluorescently labeled phosphatidylinositol 4-phosphate as the substrate and recombinant human PIP5K1C. Our assay exhibited high reproducibility, had a calculated ATP Km of 15 µM, performed with z’ values >0.7, and was used to screen a kinase-focused library of ~4,700 compounds. From this screen, we identified several potent inhibitors of PIP5K1C, including UNC3230, a compound that we recently found can reduce nociceptive sensitization in animal models of chronic pain. This novel assay will allow continued drug discovery efforts for PIP5K1C and can be easily adapted to screen additional lipid kinases