Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects

We have previously demonstrated a high antitumor potential of NOS inhibitor T1023 (1-isobutanoyl-2-isopropylisothiourea hydrobromide): antitumor antiangiogenic activity in several animal tumor models and its ability to synergistically enhance the antitumor effects of bevacizumab, cyclophosphamide and γ-radiation. At the same time, rather rapid adaptation of experimental neoplasias to T1023 treatment was often observed. We attempted to enhance the antitumor activity of this NOS inhibitor by supplementing its molecular structure with a PDK-inhibiting fragment, dichloroacetate (DCA), which is capable of hypoxia-oriented toxic effects. We synthesized compound T1084 (1-isobutanoyl-2-isopropylisothiourea dichloroacetate). Its toxic properties, NOS-inhibiting and PDK-inhibiting activity in vivo, and antitumor activity on the mouse Ehrlich carcinoma model (SEC) were investigated in compare with T1023 and Na-DCA. We found that the change of the salt-forming acid from HBr to DCA does not increase the toxicity of 1-isobutanoyl-2-isopropylisothiourea salts, but significantly expands the biochemical and anti-tumor activity. New compound T1084 realizes in vivo NOS-inhibiting and PDK-inhibiting activity, quantitatively, at the level of the previous compounds, T1023 and Na-DCA. In two independent experiments on SEC model, a pronounced synergistic antitumor effect of T1084 was observed in compare with T1023 and Na-DCA at equimolar doses. There were no signs of SEC adaptation to T1084 treatment, while experimental neoplasia rapidly desensitized to the separate treatment of both T1023 and Na-DCA. The totality of the data obtained indicates that the combination of antiangiogenic and hypoxia-oriented toxic effects (in this case, within the molecular structure of the active substance) can increase the antitumor effect and suppress the development of hypoxic resistance of neoplasias. In general, the proposed approach can be used for the design of new anticancer agents.     

Ionol phosphorus organic analogs and stabilization of levorin

Stability of levorin isolated and purified with the use of ionole phosphorus organic analogs having in their structure phosphate, phosphonate and phosphonite groups was studied. The compound having in its structure (in addition to tertiary butyl substitutes) the phosphonite group with the P-H bond increasing the compound antioxidant property was shown to have the highest stabilizing effect. The results of the study made it possible to recommend the use of the space complicated phenols with the structure fragments of the P-H bond type as antioxidants in production of levorin.     

Comparative in Vivo Assessment of Some Adverse Bioeffects of Equidimensional Gold and Silver Nanoparticles and the Attenuation of Nanosilver’s Effects with a Complex of Innocuous Bioprotectors

Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week, up to 20 injections. A group of rats was thus injected with NS after oral administration of a “bioprotective complex” (BPC) comprised of pectin, multivitamins, some amino acids, calcium, selenium, and omega-3 PUFA. After the termination of the injections, many functional and biochemical indices and histopathological features of the spleen, kidneys and liver were evaluated for signs of toxicity, and accumulation of NG or NS in these organs was measured. From the same rats, we obtained cell suspensions of different tissues for performing the RAPD test. It was demonstrated that, although both nanometals were adversely bioactive in all respects considered in this study, NS was more noxious as compared with NG, and that the BPC tested by us attenuated both the toxicity and genotoxicity of NS.     

3D crystal structure identification using fuzzy neural networks

The problem of recognizing nano-scale images of lattice projections comes down to identification of crystal lattice structure. The paper considers two types of fuzzy neural networks that can be used for tackling the problem at hand: the Takagi-Sugeno-Kang model and Mamdani-Zadeh model (the latter being a modification of the Wang-Mendel fuzzy neural network). We offer a threestage neural network learning process. In the first two stages crystal lattices are grouped in non-overlapping classes, and lattices belonging to overlapping classes are recognized at the third stage. In the research, we thoroughly investigate the applicability of the neural net models to structure identification of 3D crystal lattices.     

Moving Droplets in 3D Using Light

The emulation of the complex cellular and bacterial vesicles used to transport materials through fluids has the potential to add revolutionary capabilities to fluidic platforms. Although a number of artificial motile vesicles or microdroplets have been demonstrated previously, control over their movement in liquid in 3D has not been achieved. Here it is shown that by adding a chemical “fuel,” a photoactive material, to the droplet, it can be moved in any direction (3D) in water using simple light sources without the need for additives in the water. The droplets can be made up of a range of solvents and move with speeds as high as 10.4 mm s^?1 toward or away from the irradiation source as a result of a light‐induced isothermal change in interfacial tension (Marangoni flow). It is further demonstrated that more complex functions can be accomplished by merging a photoactive droplet with a droplet carrying a “cargo” and moving the new larger droplet to a “reactor” droplet where the cargo undergoes a chemical reaction. The control and versatility of this light‐activated, motile droplet system will open up new possibilities for fluidic chemical transport and applications.     

Hybrid flowshop with unrelated machines, sequence-dependent setup time, availability constraints and limited buffers

This paper presents a genetic algorithm for an important production scheduling problem. Since the problem is NP-hard, we focus on suboptimal scheduling solutions for the hybrid flowshop with unrelated machines, sequence-dependent setup time, availability constraints, and limited buffers. The production environment of a television assembly line for inserting electronic components is considered. The proposed genetic algorithm is a modified and extended version of the algorithm for a problem without limited buffers. It takes into account additional limited buffer constraints and uses a new crossover operator and stopping criteria. Experimental results carried out on real production settings show an improvement in scheduling when the proposed algorithm is used.     

Advanced sorbents for thermally regulated hydrogen vessel

Adsorbed hydrogen storage and transportation technology recently became competitive to compressed gas method due to high energy density capability achievements. New composite material (metal-hydride particles on the activated carbon fibre matrix) was developed as efficient hydrogen sorbent for gas storage and transportation system application. Effect of the carbon matrix nature and metal hydride content experimentally was investigated.To enhance the performance and thermodynamic efficiency of the gas storage vessel a heat pipe thermal control system was suggested. A two-dimensional transient model developed to analyze the influence of the thermal control on the operating characteristics of the sectional storage vessel with hydrogen and heat pipes.     

Comparative analysis of film formation in glow-discharge plasma in mixtures of methane with neon and argon

Concentrations of Ne, Ar, and H atoms in metastable and resonance states, concentrations of atomic hydrogen, and the growth rates of polymer films were determined in the dc glow discharge in the Ne and Ar mixtures with (1–5) % CH₄ in the pressure range of 13–520 Pa and discharge currents of 5–100 mA. The method of ellipsometry was used to control the refraction index and thickness and the composition of polymer films was analyzed with the help of the IR spectroscopy method. Mathematical simulation of discharges under the given conditions was performed. The calculation results were compared to the experimental data. It is shown that the mechanism of the ionization and dissociation processes in discharges with mixtures containing Ne differ considerably from the mechanism of these processes in discharges in mixtures with Ar, which significantly affects the film formation processes. Prolonged tests under ambient conditions showed the high stability of most of the films grown under the discharge in the mixtures of Ar and CH₄ (the film refraction index in the case of conditioning up to 10 years decreased by about 0.1 within the measurement error) and in mixtures of Ne with CH₄ (the film refraction index under prolonged conditioning features remains almost unchanged).