Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.     

The Effect of Heat Treatment on the Microstructure and Properties of Explosively Welded Titanium-Steel Plates

This paper describes a study of explosively welded titanium-carbon steel S355J2+N plates. Following the welding, plates underwent heat treatment at temperature of 600 °C for 90 min with cooling in furnace to 300 °C and in air to room temperature. The structure of the bonding was examined by using light, scanning electron (SEM) and transmission electron microscopy. The mechanical properties before and after heat treatment were examined applying three-point bending tests with cyclic loads and hardness measurements. Fracture surfaces were investigated using computer tomography and SEM. It has been found that the bonding areas are characterized by a specific chemical composition, microstructure and microhardness. Between the steel and the Ti cladding, a strongly defected transition zone was formed and melted areas with altered chemical composition were observed. It was also demonstrated that the heat treatment commonly applied to welded steel-Ti plates had a significant and negative impact on the microstructure and mechanical properties of the welded plates due to formation of brittle intermetallic phases.     

Measurement of mechanical properties in a 316L stainless steel welded joint

The aim of this study was to measure the mechanical properties of weld material taken from a single weld bead laid down on a 316L steel plate. Due to the low available volume of weld material, microsamples with a total length of 5.5 mm were used. The Digital Image Correlation method (DIC), which enables measurement of mechanical properties of very small samples, was employed for the strain measurements in a uniaxial tensile test. Samples were cut out from three different zones of the specimen: plate, weld, and the heat affected zone. The material from heat affected zone showed the highest value of the Ultimate Tensile Strength (UTS) (580 ± 7 MPa) and yield strength (339 ± 6 MPa). Plate material had lower UTS (559 ± 5 MPa) and yield strength (304 ± 7 MPa). The lowest values of UTS (526 ± 6 MPa) and yield strength (291 ± 8 MPa) have been revealed for the weld. The values obtained for UTS, yield strength and elongation to failure for the plate material were compared with data obtained using standard test specimens. No significant differences between results obtained for the microsamples and standard samples have been found.     

Evaluation of the mechanical behavior of W7-X central support connections by means of semi-automated FE analysis

The stellarator Wendelstein 7-X is under construction at the Max-Planck-Institut für Plasmaphysik in Greifswald. Its superconducting coil system is fixed by a massive structure. During machine operation the coils exert high forces and moments against each other and the central support structure (CSS). Therefore, the detailed analysis of the coil to CSS connections, the so-called central support elements (CSE), is a critical item. The major details of the design have been frozen; nevertheless, there is still need for detailed analysis of the CSEs due to assembly issues, and later on for exploring operational limits of the machine. These analyses have to be performed quickly, reliably, and shall provide results in a standardized form to enable timely responses to the assembly team. Special numerical tools – finite element (FE) parametric models of CSEs – have been developed for the purpose of such analyses. In the models, the geometry, material properties, contact conditions, loads as well as results presentation are defined in a parametric way. The use of the developed models for the definition of the final weld parameters, bolt preloads, assessment of acceptable tolerances, and optimal positions of the CSE-wedges before welding is also discussed.     

XPS studies of perovskites surface instability caused by Ar+ ion and electron bombardment and metal deposition

X-ray Photoelectron Spectroscopy (XPS) was used to study the influence of low energy Ar⁺ ion bombardment, electron bombardment and Pt deposition on the SrTiO₃ (STO) single crystal electronic structure. Atomic composition changes were found and attributed to chemical reconstruction of the STO surface. A clear correlation between the presence of conducting, low Ti oxidation states in valence band and core level changes was detected. A strong effect caused by electron irradiation was ascribed to the electroreduction process. The influence of lanthanum doping on surface instability of STO was also discussed. The La doped sample (STO: 3,75% La) was found to be modified upon Pt metal deposition to a higher degree than pure STO crystal.     

Surface potential measurements of Langmuir films of azo dye/liquid crystal mixtures

Two-component films of a non-amphiphilic azo dye and a liquid crystal with strongly polar –CN group were studied at an air–water interface on the basis of the surface potential–mean molecular area dependence recorded simultaneously with the surface pressure–mean molecular area isotherm. Additionally, the morphology of the films was monitored with the aid of Brewster angle microscope. A conventional Langmuir technique was used to form dye/liquid crystal films during reduction and expansion of an area occupied by the molecules. From the surface potential value, the effective dipole moment in the first monolayer formed on the water was calculated. Moreover, the number of molecules with dipole moments directed from the water to the air with respect to those directed towards water was estimated. The influence of the two components' miscibilities upon the surface potential after addition of the dye to the liquid crystal was determined.     

Highly scalable and robust rule learner: performance evaluation and comparison.

Business intelligence and bioinformatics applications increasingly require the mining of datasets consisting of millions of data points, or crafting real-time enterprise-level decision support systems for large corporations and drug companies. In all cases, there needs to be an underlying data mining system, and this mining system must be highly scalable. To this end, we describe a new rule learner called DataSqueezer. The learner belongs to the family of inductive supervised rule extraction algorithms. DataSqueezer is a simple, greedy, rule builder that generates a set of production rules from labeled input data. In spite of its relative simplicity, DataSqueezer is a very effective learner. The rules generated by the algorithm are compact, comprehensible, and have accuracy comparable to rules generated by other state-of-the-art rule extraction algorithms. The main advantages of DataSqueezer are very high efficiency, and missing data resistance. DataSqueezer exhibits log-linear asymptotic complexity with the number of training examples, and it is faster than other state-of-the-art rule learners. The learner is also robust to large quantities of missing data, as verified by extensive experimental comparison with the other learners. DataSqueezer is thus well suited to modern data mining and business intelligence tasks, which commonly involve huge datasets with a large fraction of missing data.     

Comparison of systematic search and database methods for constructing segments of protein structure

Two principal methods of determining the conformation of shortpieces of polypeptide backbone in proteins have been developed:using a database of known structures and systematicallygeneratingall conformations. In this paper, we compare the effectivenessof these two techniques. The completeness of the database forsegments of different lengths is examined and it is found tocontain most conformations for segments seven residues long,but to deteriorate rapidly for longer regions. When the databasesegment is to be incorporated into the rest of a structure,at least seven residues are required to build four new residues,because of the need to positionthe segment relative to the restof the structure.It is found that such positioning using flankingresidues results in large errors in the inserted region. Weconclude that the database method is currently not effectivefor comparative modeling, even for short segments. The systematicsearchprocedure is found to generate almost all structures of shortsegments found in proteinsIn contrast to the database method,low root mean square error structures are obtained for a setof trial segments embedded in the rest of a protein structure.Thus, it should be considered the method of choice.