Existence and approximation of slow integral manifolds in some degenerate cases

We consider singularly perturbed differential systems whose degenerate equations have an isolated but not simple solution. In that case, the standard theory to establish a slow integral manifold near this solution does not work. Applying scaling transformations and using the technique of gauge functions we reduce the original singularly perturbed problem to a regularized one such that the existence of slow integral manifolds can be established by means of the standard theory of singular perturbations. We illustrate our method by several examples

Integral manifolds for slow-fast differential systems loosing their attractivity in time

The work is devoted to the investigation of the integral manifolds of the nonautonomous slow-fast systems, which change their attractivity in time. The method used here is based on gluing attractive and repulsive integral manifolds by using an additional function

A new type of travelling wave solutions

We study the existence of combustion waves for an autocatalytic reaction in the non-adiabatic case. Basing on the fact that the reaction system has canard solutions separating the slow combustion regime from the explosive one, we prove by applying the geometric theory of singularly perturbed differential equations the existence of a new type of travelling waves solutions, the so-called canard travelling waves

Research of the thorium purification at monazite refinement processes

This paper is aimed to the research of the thorium purification processes at monazite refinement processes. We have investigated different solution containing thorium with different mix of rare-earth elements. It was found that the application of cation resin is well- recommended if we want to reach the highest yields of thorium purification process

Detection of Coherent Terahertz Radiation from a High-Temperature Superconductor Josephson Junction by a Semiconductor Quantum-Dot Detector

We examine the application of Josephson radiation emitters to spectral calibration of single-photon-resolving detectors. Josephson junctions are patterned in a YBCO film on a bicrystal sapphire substrate and are voltage controlled to generate radiation in the frequency range of 0.05-1 THz. The detector used in this work consists of a gate-defined quantum-dot photon-to-charge transducer coupled to a single-electron transistor. Both the emitter and the detector are equipped with a matching on-chip wide-band antenna. The combination of a tuneable emitter and detector allows us to determine the efficacy of the YBCO emitter and also to analyze the elementary processes involved in the detection

Study of exclusive one-pion and one-eta production using hadron and dielectron channels in pp reactions at kinetic beam energies of 1.25 GeV and 2.2 GeV with HADES

We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions

Computational Prediction of Heme-Binding Residues by Exploiting Residue Interaction Network

Computational identification of heme-binding residues is beneficial for predicting and designing novel heme proteins. Here we proposed a novel method for heme-binding residue prediction by exploiting topological properties of these residues in the residue interaction networks derived from three-dimensional structures. Comprehensive analysis showed that key residues located in heme-binding regions are generally associated with the nodes with higher degree, closeness and betweenness, but lower clustering coefficient in the network. HemeNet, a support vector machine (SVM) based predictor, was developed to identify heme-binding residues by combining topological features with existing sequence and structural features. The results showed that incorporation of network-based features significantly improved the prediction performance. We also compared the residue interaction networks of heme proteins before and after heme binding and found that the topological features can well characterize the heme-binding sites of apo structures as well as those of holo structures, which led to reliable performance improvement as we applied HemeNet to predicting the binding residues of proteins in the heme-free state. HemeNet web server is freely accessible at http://mleg.cse.sc.edu/hemeNet/

Functional classification of proteins based on projection of amino acid sequences: application for prediction of protein kinase substrates

<p>Abstract</p> <p>Background</p> <p>The knowledge about proteins with specific interaction capacity to the protein partners is very important for the modeling of cell signaling networks. However, the experimentally-derived data are sufficiently not complete for the reconstruction of signaling pathways. This problem can be solved by the network enrichment with predicted protein interactions. The previously published <it>in silico </it>method PAAS was applied for prediction of interactions between protein kinases and their substrates.</p> <p>Results</p> <p>We used the method for recognition of the protein classes defined by the interaction with the same protein partners. 1021 protein kinase substrates classified by 45 kinases were extracted from the Phospho.ELM database and used as a training set. The reasonable accuracy of prediction calculated by leave-one-out cross validation procedure was observed in the majority of kinase-specificity classes. The random multiple splitting of the studied set onto the test and training set had also led to satisfactory results. The kinase substrate specificity for 186 proteins extracted from TRANSPATH^®database was predicted by PAAS method. Several kinase-substrate interactions described in this database were correctly predicted. Using the previously developed ExPlain™ system for the reconstruction of signal transduction pathways, we showed that addition of the newly predicted interactions enabled us to find the possible path between signal trigger, TNF-alpha, and its target genes in the cell.</p> <p>Conclusions</p> <p>It was shown that the predictions of protein kinase substrates by PAAS were suitable for the enrichment of signaling pathway networks and identification of the novel signaling pathways. The on-line version of PAAS for prediction of protein kinase substrates is freely available at <url>http://www.ibmc.msk.ru/PAAS/</url>.</p

New Synthetic Thrombin Inhibitors: Molecular Design and Experimental Verification

BACKGROUND: The development of new anticoagulants is an important goal for the improvement of thromboses treatments. OBJECTIVES: The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. METHODS: Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. RESULTS: New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. CONCLUSIONS: The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications