Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

Design of Lu2O3-reinforced Cf/SiC-ZrB2-ZrC ultra-high temperature ceramic matrix composites: Wetting and interfacial reactivity by ZrSi2 based alloys

The wettability and infiltration of molten ZrSi₂ and ZrSi₂-Lu₂O₃ alloys into C_f/SiC and B₄C-infiltrated C_f/SiC composites were investigated to understand the interfacial interactions that occur during the development of C_f/SiC-ZrC and C_f/SiC-ZrB₂-ZrC-Lu₂O₃ materials. A significant evaporation of Si from the liquid affected the wetting behaviour of the alloy when tested in a vacuum at 1670 °C. The better wetting and spreading of the alloy over the surface was observed for the composites with lower overall porosity (12 %). On the other hand, the formation of an outer dense layer, followed up by the uniform infiltrated region up to ～ 1 mm was observed for the C_f/SiC with higher porosity (21 %). The infiltrated alloy reacted with SiC matrix to form ZrC or with B₄C-infiltrated SiC matrix to form ZrB₂-ZrC-SiC. The Lu₂O₃ particles were not wetted by the melt, and were pushed away of the reaction zone by the solidification front.     

Corrosion of NiTi Wires with Cracked Oxide Layer

Corrosion behavior of superelastic NiTi shape memory alloy wires with cracked TiO₂ surface oxide layers was investigated by electrochemical corrosion tests (Electrochemical Impedance Spectroscopy, Open Circuit Potential, and Potentiodynamic Polarization) on wires bent into U-shapes of various bending radii. Cracks within the oxide on the surface of the bent wires were observed by FIB–SEM and TEM methods. The density and width of the surface oxide cracks dramatically increase with decreasing bending radius. The results of electrochemical experiments consistently show that corrosion properties of NiTi wires with cracked oxide layers (static load keeps the cracks opened) are inferior compared to the corrosion properties of the straight NiTi wires covered by virgin uncracked oxides. Out of the three methods employed, the Electrochemical Impedance Spectroscopy seems to be the most appropriate test for the electrochemical characterization of the cracked oxide layers, since the impedance curves (Nyquist plot) of differently bent NiTi wires can be associated with increasing state of the surface cracking and since the NiTi wires are exposed to similar conditions as the surfaces of NiTi implants in human body. On the other hand, the potentiodynamic polarization test accelerates the corrosion processes and provides clear evidence that the corrosion resistance of bent superelastic NiTi wires degrades with oxide cracking.     

Simulations of Self-Expanding Braided Stent Using Macroscopic Model of NiTi Shape Memory Alloys Covering R-Phase

Self-expanding stents or stentgrafts made from Nitinol superelastic alloy are widely used for a less invasive treatment of disease-induced localized flow constriction in the cardiovascular system. The therapy is based on insertion of a stent into a blood vessel to maintain the inner diameter of the vessel; it provides highly effective results at minimal cost and with reduced hospital stays. However, since stent is an external mechanical healing tool implemented into human body for quite a long time, information on the mechanical performance of it is of fundamental importance with respect to patient’s safety and comfort. Advantageously, computational structural analysis can provide valuable information on the response of the product in an environment where in vivo experimentation is extremely expensive or impossible. With this motivation, a numerical model of a particular braided self-expanding stent was developed. As a reasonable approximation substantially reducing computational demands, the stent was considered to be composed of a set of helical springs with specific constrains reflecting geometry of the structure. An advanced constitutive model for NiTi-based shape memory alloys including R-phase transition was employed in analysis. Comparison to measurements shows a very good match between the numerical solution and experimental results. Relation between diameter of the stent and uniform radial pressure on its surface is estimated. Information about internal phase and stress state of the material during compression loading provided by the model is used to estimate fatigue properties of the stent during cyclic loading.     

Development and characterisation of a Y2Ti2O7-based glass-ceramic as a potential oxidation protective coating for titanium suboxide (TiOx)

A silica-based glass-ceramic, with Y₂Ti₂O₇ as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiO_x) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y₂Ti₂O₇ and CaAl₂Si₂O₈ as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiO_x material.     

How the interactions with humic acids affect the mobility of ionic dyes in hydrogels – Results from diffusion cells

The complexation of charged compounds by humic acids represents the process of exceptional environmental importance. Nevertheless, traditional methods utilized in the complexation studies do not address the way, how these interactions affect the transport of ions in humic-rich environments. To overcome this dilemma, the diffusion cells technique is proposed as an innovative reactivity mapping technique. Using this method, the diffusion of methylene blue was studied in aqueous solutions and in agarose gels with and without the addition of humic acids. Experimental results clearly illustrate the immobilizing effects of humic acids on the transport of methylene blue in gels. The partitioning of methylene blue at the solution-gel interface and the specific interactions between methylene blue and humic acids is discussed on the basis of experimental data. Effective structural parameters of hydrogels (effective porosity, tortuosity factor) were calculated, as well as some standard diffusion and interaction parameters (diffusion and partition coefficients and apparent equilibrium constants).     

Wire electrical discharge machinable SiC with GNPs and GO as the electrically conducting filler

SiC based composites filled with graphene nano-platelets (GNPs) or graphene oxide (GO) prepared by rapid hot-pressing exhibit sufficient electrical conductivity for their machinability by wire electro-discharge machining (WEDM). Composites microstructure anisotropy caused by graphene alignment as a consequence of rapid hot pressing was confirmed by measuring of electrical conductivity and thermal diffusivity. Electrical conductivity increased significantly with increased weight fraction of graphene in both measured directions. Highest value of 2031 S/m was obtained for composites with 15 wt. % of GNPs in parallel direction and only 1246 S/m in perpendicular direction to aligned GNPs. Thermal diffusivity is 63.3 mm²/s in parallel and only 23.3 mm²/s in perpendicular direction. The increase of the electrical conductivity has resulted in successful WEDM. The MRR was almost doubled when the filler concentration increased from 5 wt. % GNPs/GO to 15 wt. % GNPs. At the same time, the surface roughness decreased.     

Copper-Tungsten Composites Sprayed by HVOF

Copper and copper-tungsten composite coatings were produced by high-velocity oxy-fuel spraying (HVOF). After initial optimization of the spraying parameters, coatings of various compositions were made and their structure, composition, mechanical, thermal, and electrical properties were characterized. The HVOF technique was able to produce rather dense coatings with minimal oxide content and relatively good mechanical and thermal properties compared to, for example, plasma-sprayed coatings; however, the achieved tungsten content was quite low.     

Configurations of diastereomeric hydroxyethylene isosteres strongly affect biological activities of a series of specific inhibitors of human-immunodeficiency-virus proteinase

Human immunodeficiency virus (HIV) proteinase (PR) represents an important target for antiviral chemotherapy. We present an analysis of inhibitory activities of a series of pseudopeptide inhibitors of HIV-1 PR. All inhibitors were N-protected tetrapeptides with the scissile bond replaced by a nonhydrolysable hydroxyethylene or hydroxyethylamine isostere. To elucidate subtle structural requirements of the PR binding cleft, we synthesised inhibitors with four combinations of configurations at the asymmetric carbons of the isostere. Compounds were tested in vitro using purified recombinant enzyme and a chromogenic peptide substrate. The differences in inhibition constants between individual diastereoisomers reached three orders of magnitude. The most active hydroxyethylene-containing inhibitor possessed the 2R,4S,5S configuration at the isostere. Inhibitor activity was also tested in mammalian cell culture by analysing reduction of viral polyprotein processing and virus infectivity. The results obtained in tissue culture were generally in agreement with the in vitro data, giving a similar order of potency for the individual diastereoisomers. The most active compounds completely blocked production of infectious virus. A simulation method for interaction was employed to build a model of the inhibitors in the PR active site, to identify the interactions responsible for the differences in activities of individual stereoisomers, and to estimate the relative contribution of individual structural features to the overall inhibitory activity.