Influence of the Ti-TiN-(Y,Ti,Al)N Nanolayer Coating Deposition Process Parameters on Cutting Tool Oxidative Wear during Steel Turning.

Ti-TiN-(Y,Ti,Al)N coatings with a three-layer architecture (adhesive Ti layer, transition TiN layer, and wear-resistant (Y,Ti,Al)N layer) were studied. When depositing coatings, three arc current values of the yttrium cathode were used: 65, 85, and 105 A. The yttrium contents in the coatings were 30, 47, and 63 at. %, respectively. When turning 1045 steel, a coating with 30 at. % yttrium showed better wear resistance compared to a commercial (Ti,Cr,Al)N coating. The coating with 63 at. % yttrium did not show an increase in wear resistance compared to the uncoated sample. Nanolayers with a high yttrium content are oxidized more actively compared to nanolayers with a high titanium content. Phase analysis shows partial retention of the initial phases (Y,Ti,Al)N and (Ti,Y,Al)N during the formation of the Y2O3 oxide phase in the outer layers of the coating and the presence of only the initial phases in the deep layers. Coating nanolayers with high contents of aluminum and yttrium lose their original structure to a greater extent during oxidation compared to layers without aluminum.

An organometallic analogue of combretastatin A-4 and its apoptosis-inducing effects on lymphoma, leukemia and other tumor cells in vitro.

Hexacarbonyl[1,3-dimethoxy-5-((4'-methoxyphenyl)ethynyl)benzene]dicobalt (NAHO27), an organometallic analogue of combretastatin A-4, has been synthesized and its activity against lymphoma, leukemia, breast cancer and melanoma cells has been investigated. It was shown that NAHO27 specifically induces apoptosis in BJAB lymphoma and Nalm-6 leukemia cells at low micromolar concentration and does not affect normal leukocytes in vitro. It also proved to be active against vincristine and daunorubicin resistant leukemia cell lines with p-glycoprotein-caused multidrug resistance and showed a pronounced (550%) synergistic effect when co-applied with vincristine at very low concentrations. Mechanistic investigations revealed NAHO27 to induce apoptosis via the mitochondrial (intrinsic) pathway as reflected by the processing of caspases 3 and 9, the involvement of Bcl-2 and smac/DIABLO, and the reduction of mitochondrial membrane potential. Gene expression analysis and protein expression analysis via western blot showed an upregulation of the proapoptotic protein harakiri by 9%.

Head-to-Head Comparison of Selected Extra- and Intracellular CO-Releasing Molecules on Their CO-Releasing and Anti-Inflammatory Properties.

Over the past decade, a variety of carbon monoxide releasing molecules (CORMs) have been developed and tested. Some CORMs spontaneously release CO once in solution, while others require a trigger mechanism to release the bound CO from its molecular complex. The modulation of biological systems by CORMs depends largely on the spatiotemporal release of CO, which likely differs among the different types of CORMs. In spontaneously releasing CORMs, CO is released extracellularly and crosses the cell membrane to interact with intracellular targets. Other CORMs can directly release CO intracellularly, which may be a more efficient method to modulate biological systems. In the present study, we compared the efficacy of extracellular and intracellular CO-releasing CORMs that either release CO spontaneously or require an enzymatic trigger. The efficacy of such CORMs to modulate HO-1 and VCAM-1 expression in TNF-α-stimulated human umbilical vein endothelial cells (HUVEC) was evaluated.

Development of a Model of Crack Propagation in Multilayer Hard Coatings under Conditions of Stochastic Force Impact.

The article deals with the problems of cracking in the structure of multilayered coatings under the conditions of stochastic loading process. A mathematical model has been proposed in order to predict the crack propagation velocity in the coating while taking the influence of interlayer interfaces into account. A technique for calculating the probability density distribution of the coating fracture (failure rate) has been developed. The probability of a change in the crack growth direction is compared with the experimental data that were obtained as a result of the studies focused on the pattern of cracking in the Zr,Nb-(Zr,Nb)N-(Zr,Nb,Al)N and Ti-TiN-(Ti,Cr,Al)N coatings under the conditions of the real stochastic loading of cutting tools during the turning. The influence of the crystalline structure of the coating on the cracking pattern has been studied. The investigation has found the significant effect of the crystalline structure of the coating layers on the cracking pattern.

Crystallization Features of Amorphous Rapidly Quenched High Cu Content TiNiCu Alloys upon Severe Plastic Deformation.

In recent years, the methods of severe plastic deformation and rapid melt quenching have proven to be an effective tool for the formation of the unique properties of materials. The effect of high-pressure torsion (HPT) on the structure of the amorphous alloys of the quasi-binary TiNi-TiCu system with a copper content of more than 30 at.% produced by melt spinning technique has been analyzed using the methods of scanning electron microscopy, X-ray diffraction analysis, and differential scanning calorimetry (DSC). The structure examinations have shown that the HPT of the alloys with a Cu content ranging from 30 to 40 at.% leads to nanocrystallization from the amorphous state. An increase in the degree of deformation leads to a substantial change in the character of the crystallization reflected by the DSC curves of the alloys under study. The alloys containing less than 34 at.% Cu exhibit crystallization peak splitting, whereas the alloys containing more than 34 at.% Cu exhibit a third peak at lower temperatures. The latter effect suggests the formation of regions of possible low-temperature crystallization. It has been established that the HPT causes a significant decrease in the thermal effect of crystallization upon heating of the alloys with a high copper content relative to that of the initial amorphous melt quenched state.

Black Carbon Sources Constrained by Observations in the Russian High Arctic.

Understanding the role of short-lived climate forcers such as black carbon (BC) at high northern latitudes in climate change is hampered by the scarcity of surface observations in the Russian Arctic. In this study, highly time-resolved Equivalent BC (EBC) measurements during a ship campaign in the White, Barents, and Kara Seas in October 2015 are presented. The measured EBC concentrations are compared with BC concentrations simulated with a Lagrangian particle dispersion model coupled with a recently completed global emission inventory to quantify the origin of the Arctic BC. EBC showed increased values (100-400 ng m-3) in the Kara Strait, Kara Sea, and Kola Peninsula and an extremely high concentration (1000 ng m-3) in the White Sea. Assessment of BC origin throughout the expedition showed that gas-flaring emissions from the Yamal-Khanty-Mansiysk and Nenets-Komi regions contributed the most when the ship was close to the Kara Strait, north of 70° N. Near Arkhangelsk (White Sea), biomass burning in mid-latitudes, surface transportation, and residential and commercial combustion from Central and Eastern Europe were found to be important BC sources. The model reproduced observed EBC concentrations efficiently, building credibility in the emission inventory for BC emissions at high northern latitudes.

Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids.

A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine-step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect).

Design, synthesis, and functional evaluation of CO-releasing molecules triggered by Penicillin†G amidase as a model protease.

Protease-triggered CO-releasing molecules (CORMs) were developed. The viability of the approach was demonstrated through the synthesis of compounds consisting of an η(4) -oxydiene-Fe(CO)3 moiety connected to a penicillin G amidase (PGA)-cleavable unit through a self-immolative linker. The rate of PGA-induced hydrolysis was investigated by HPLC analysis and the subsequent CO release was quantitatively assessed through headspace gas chromatography. In an in vitro assay with human endothelial cells, typical biological effects of CO, that is, inhibition of the inflammatory response and the induction of heme oxygenase-1 expression, were observed only upon co-administration of the CORM and PGA. This work forms a promising basis for the future development of protease-specific CORMs for potential medicinal applications.

Hydrogen-bond-assisted organocatalytic acetalization of secondary alcohols: experimental and theoretical studies.

An efficient method was developed for the acetalization of secondary alcohols in the presence of simple protic pyridinium salts. Direct correlations between the structure and activity of the synthesized catalysts were described. Stabilization via hydrogen bonding of the hemiacetal intermediate by the pyridine derivatives, along with an appropriate increase in the reaction rate, was revealed. The nature of the observed experimental acceleration of the examined reactions catalyzed by pyridinium salts comprising electron-withdrawing groups at certain positions of the pyridinium ring was studied. In this vein, the interpretation of the hydrogen-bonded pretransition-state complexes and transition-state complexes with strong catalysts was also discussed in terms of partial proton transfer. It was concluded that optimized pretransition-state complexes of the catalyst and reactant are useful for the prediction of catalyst efficiency prior to the experiment.

Synthesis and biological evaluation of furanoallocolchicinoids.

A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell lines (AsPC-1, HEK293, and Jurkat) as well as against Wnt-1 related murine epithelial cell line W1308. The results of in vitro experiments demonstrated that the major effect of these compounds was the induction of cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding. In vivo testing of the most potent furanoallocolchicinoid 10c using C57BL/6 mice inoculated with Wnt-1 tumor cells indicated significant inhibition of the tumor growth.

Total synthesis of indole-derived allocolchicine analogues exhibiting strong apoptosis-inducing activity.

A series of novel pyrrolo-allocolchicine derivatives (containing a 1-methyl-1H-indol-5-yl moiety replacing ring C) was synthesized. The tetracyclic ring system was constructed by Suzuki-Miyaura cross-coupling of a 1-methylindole-5-boronate with an ortho-iodo-dihydrocinnamic acid derivative and subsequent intramolecular Friedel-Crafts acylation. After reduction of the resulting ketone, the nitrogen functionality was introduced in a Mitsunobu-type reaction by using zinc azide followed by LiAlH(4) reduction. Structural assignments were supported by X-ray crystallography. The compounds synthesized were then tested against BJAB tumor cells and found to exhibit pronounced cytotoxic activity (proliferation inhibition and apoptosis induction). The ketone 24 b was even active at sub-nanomolar concentration. In addition, the antitumor potential of the compounds was confirmed by using B lymphoid cell lines.