Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters.

The aim of this work is to verify the possibility of transport of 26 biologically active ultrashort peptides (USPs) into cells via LAT and PEPT family transporters. Molecular modeling and computer-assisted docking of peptide ligands revealed that the size and structure of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analysis of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters has been carried out. The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides, for which no biological activity has been established. This indicates an important possible role which LAT and PEPT family transporters may play in a variety of biological activities of the 26 biologically active peptides under investigation in this study. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp- or Glu- amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide are found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters. The data obtained lead to new prospects for further study of the mechanisms of transport of USP-based drugs into the cell and design of new antitumor drugs.

Effect of Different Tool Probe Profiles on Material Flow of Al-Mg-Cu Alloy Joined by Friction Stir Welding.

Friction Stir Welding (FSW) was utilized to butt-join 2024-T4 aluminum alloy plates of 1.9 mm thickness, using tools with conical and tapered hexagonal probe profiles. The characteristic effects of FSW using tools with tapered hexagonal probe profiles include an increase in the heat input and a significant modification of material flow, which have a positive effect on the metallurgical characteristics and mechanical performance of the weld. The differences in mechanical properties were interpreted through macrostructural changes and mechanical properties of the welded joints, which were supported by numerical simulation results on temperature distribution and material flow. The material flow resulting from the tapered hexagonal probe was more complicated than that of the conical probe. If in the first case, the dynamic viscosity and strain rate are homogeneously distributed around the probe, but in the case of the tapered hexagonal probe tool, the zones with maximum values of strain rates and minimum values of dynamic viscosity are located along the six tapered edges of the probe.

Mode Coupling at around M-Point in PZT.

The question of the microscopic origin of the M-superstructure and additional satellite peaks in the Zr-rich lead zirconate-titanate is discussed for nearly 50 years. Clear contradiction between the selection rules of the critical scattering and the superstructure was found preventing unambiguous attributing of the observed superstructure either to the rotation of the oxygen octahedra or to the antiparallel displacements of the lead cations. Detailed analysis of the satellite pattern explained it as the result of the incommensurate phase transition rather than antiphase domains. Critical dynamics is the key point for the formulated problems. Recently, the oxygen tilt soft mode in the PbZr0.976Ti0.024O3 (PZT2.4) was found. But this does not resolve the extinction rules contradiction. The results of the inelastic X-ray scattering study of the phonon spectra of PZT2.4 around M-point are reported. Strong coupling between the lead and oxygen modes resulting in mode anticrossing and creation of the wide flat part in the lowest phonon dispersion curves is identified. This flat part corresponds to the mixture of the displacements of the lead and oxygen ions and can be an explanation of the extinction rules contradiction. Moreover, a flat dispersion surface is a typical prerequisite for the incommensurate phase transition.

Metallurgical and Mechanical Characterization of High-Speed Friction Stir Welded AA 6082-T6 Aluminum Alloy.

The objective of this study was to investigate the effect of the high welding speed on the mechanical properties and their relations to microstructural characteristics of butt friction stir welded joints with the use of 6082-T6 aluminum alloy. The aluminum sheets of 2.0 mm thick were friction stir welded at low (conventional FSW) and high welding speeds (HSFSW) of 200 and 2500 mm/min, respectively. The grain size in the nugget zone (NZ) was decreased; the width of the softened region was narrowed down as well as the lowest microhardness value located in the heat-affected zone (HAZ) was enhanced by HSFSW. The increasing welding speed resulted in the higher ultimate tensile strength and lower elongation, but it had a slight influence on the yield strength. The differences in mechanical properties were explained by analysis of microstructural changes and tensile fracture surfaces of the welded joints, supported by the results of the numerical simulation of the temperature distribution and material flow. The fracture of the conventional FSW joint occurred in the HAZ, the weakest weld region, while all HSFSW joints raptured in the NZ. This demonstrated that both structural characteristics and microhardness distribution influenced the actual fracture locations.