Synthesis and Anticancer Properties of Oxazepines Related to Azaisoerianin and IsoCoQuines

In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA-4 having significant antitumor properties. Among them, three oxazepin-9-ol derivatives display a nanomolar or a sub-nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC₅₀ value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells. Molecular modeling studies perfectly corroborates these promising results.     

Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.     

Evaluation of major factors influencing the TBC topcoat formation in axial suspension plasma spraying (SPS)

Suspension plasma spraying (SPS) is ideally suited to produce porous or dense columnar, strain-tolerant thermal barrier coatings (TBCs) and also offers the possibility of producing other microstructures such as feathery and dense vertically cracked coatings. The specific properties of the TBC are significantly influenced by the formed microstructure, that is, affected by feedstock material and process parameters. In this work, the effects of various process parameters in the SPS process are investigated. It was found that the suspension feed rate has a significant effect on the microstructure, especially on the column density of the coating, whereas the suspension solids content mainly affects the coating porosity. Additionally, the surface roughness and topography of the bond coat are crucial for the formation of columnar coatings and were therefore investigated. Despite comparable roughness values for as-sprayed bond coats for high velocity oxy fuel and vacuum plasma spray produced coatings, the surface structures differ significantly from each other and affect the microstructure of the deposited topcoat. Characterization of mechanical properties by means of micro-indenter can be suitable for columnar coatings to determine Young's modulus within a column. However, due to the heterogeneity of the coating, the method is not suitable to describe the mechanical properties of the topcoat.     

Sol–Gel Processing and Microwave Characteristics of Ba(Mg⅓Ta⅔)O3 Dielectrics

The sol–gel method has been developed for the preparation of pure Ba(Mg_1/3Ta_2/3)O₃ ceramics. This involves the reaction of the heterometallic alkoxide Ta₂Mg(OEt)₁₂ with hydrated barium hydroxide Ba(OH)₂·8H₂O. Complete crystallization of the sol–gel-derived powder is achieved at 600°C, leading to a cubic perovskite type phase. After sintering at 1400°C (2–5 h), a trigonal cell arises from Mg–Ta ordering (the degree of order is greater than 0.9), and about 98.5% of the theoretical density is obtained. Preliminary microwave dielectric measurements show that the dielectric constant and the unloaded Q _u of the ceramics are 24.2 and 6750, respectively, at 7.7 GHz.     

In vitro comparison of hepatic metabolism of 9cis-11 trans and 10trans-12cis isomers of CLA in the rat

Hepatic metabolism of the two main isomers of CLA (9cis-11 trans, 10trans-12cisC_18∶2) was compared to that of oleic acid (representative of the main plasma FA) in 16 rats by using the in vitro method of incubated liver slices. Liver tissue samples were incubated at 37°C for 17h under an atmosphere of 95% O₂/5%CO₂ in a medium supplemented with 0.75 mM of FA mixture (representative of circulating nonesterified FA) and with 55 μM [1-¹⁴C]9cis-11 trans C_18∶2, [1-¹⁴C]10trans-12cis C_18∶2, or [1-¹⁴C]oleate. The uptake of CLA by hepatocytes was similar for both isomers (9%) and was three times higher (P<0.01) than for oleate (2.6%). The rate of CLA isomer oxidation was two times higher (49 and 40% of incorporated amounts of 9cis-11 trans and 10trans-12 cis, respectively) than that of oleate (P<0.01). Total oxidation of oleate and CLA isomers into [¹⁴CO₂] was low (2 to 7% of total oxidized FA) compared to the partial oxidation (93 to 98%) leading to the production of [¹⁴C] acid-soluble products. CLA isoemrs escaping from catabolism were both highly desaturated (26.7 and 26.8%) into conjugated 18∶3. Oleate and CLA isomers were mainly esterified into neutral lipids (30%). They were slowly secreted as parts of VLDL particles (<0.4% of FA incorporated into cells), the extent of secretion of oleate and of 10trans-12 cis being 2.2-fold higher than that of 9cis-11 trans (P<0.02). In conclusion, this study clearly showed that both CLA isomers were highly catabolized by hepatocytes, reducing their availability for peripheral tissues. Moreover, more than 25% of CLA escaping from catabolism was converted into conjugated 18∶3, the biological properties of which remain to be elucidated.     

Static and Dynamic Mechanical Behavior of Electron Beam‐Cured Monomer and Monomer/Liquid Crystal Systems

Summary: This paper discusses static and dynamic mechanical properties of electron beam‐cured mixtures made of the nematic liquid crystal (LC) E7 and either tripropyleneglycol diacrylate (TPGDA) or propoxylated glycerol triacrylate (GPTA) as monomers differing essentially by their functionality. Dilution of the initial mixture with LC leads to a significant weakening of the film mechanical strength. Strong effects were found on Young modulus and rubbery state modulus. As the concentration of LC increases, these mechanical parameters drop significantly together with the glass transition temperature of the polymer showing a plasticizing effect. The results for the glass transition temperatures for the polymer and the LC were confirmed by thermograms obtained by differential scanning calorimetry.

Storage tensile modulus versus temperature of EB‐cured TPGDA/E7 films for different LC concentrations.     

CFD as an approach to understand flammable dust 20 L standard test: Effect of the ignition time on the fluid flow

A computational study based on the Euler–Lagrange approach was developed for the characterization of flammable dusts in the 20 L sphere standard test. The aim of the study was to analyze some parameters that might affect the experimental data (e.g., cold turbulence and particle size). The turbulence of a wheat starch cloud was described with the Detached Eddy Simulation model. Both the pressure of the system and the RMS velocity were compared with the flow patterns established with a particle image velocimetry analysis. It was concluded that the rebound nozzle forms a cloud that is composed by clumps. This fact implies dissimilarities between the local concentrations and the nominal value. Finally, a granulometric analysis established that the mean diameter of the particle size distribution (PSD) decreased by 69% during the dispersion. Thus, it is suggested to consider the PSD at the ignition zone rather than the PSD of the sample. © 2017 American Institute of Chemical Engineers AIChE J, 63: 42–54, 2018     

A computational study of the effects of multiphase dynamics in catalytic upgrading of biomass pyrolysis vapor

A recurring challenge among the variety of existing biomass‐to‐biofuel conversion technologies is the need to ensure optimal and homogeneous contact between the various phases involved. The formulation of robust design rules from an empirical standpoint alone remains difficult due to the wide range of granular flow regimes coexisting within a given reactor. In this work, a volume‐filtered Eulerian‐Lagrangian framework is employed that solves chemically reacting flows in the presence of catalytic particles. The simulation strategy is used to quantify the role of the particle clustering on catalytic upgrading of biomass pyrolysis vapor in risers. It is shown that particle clustering can reduce the catalytic conversion rate of biomass pyrolysis vapors by up to about 50%. The simulation results are also compared with an engineering model based on continuously stirred tank reactor (CSTR). A one‐dimensional Reynolds‐averaged transport equation is derived, and the unclosed terms that account for the heterogeneity caused by clusters are evaluated. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3341–3353, 2018     

Indoloazepinone‐Constrained Oligomers as Cell‐Penetrating and Blood–Brain‐Barrier‐Permeating Compounds

Non‐cationic and amphipathic indoloazepinone‐constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l ‐Aia‐Xxx]_n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc‐[l ‐Aia‐Gly]_2,4‐OBn oligomers 12 and 13 and Boc‐[l ‐Aia‐β³‐h‐l ‐Ala]_2,4‐OBn oligomers 16 and 17 were totally or partially disordered, Boc‐[l ‐Aia‐l ‐Ala]₂‐OBn ( 14 ) induced a typical turn stabilized by C₅‐ and C₇‐membered H‐bond pseudo‐cycles and aromatic interactions. Boc‐[l ‐Aia‐l ‐Ala]₄‐OBn ( 15 ) exhibited a unique structure with remarkable T‐shaped π‐stacking interactions involving the indole rings of the four l ‐Aia residues forming a dense hydrophobic cluster. All of the proposed FITC‐6‐Ahx‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers 19 – 23 , with the exception of FITC‐6‐Ahx‐[l ‐Aia‐Gly]₄‐NH₂ ( 18 ), were internalized by MDA‐MB‐231 cells with higher efficiency than the positive references penetratin and Arg₈. In parallel, the compounds of this series were successfully explored in an in vitro blood–brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers in the PAMPA model, Ac‐[l ‐Aia‐l ‐Arg]₄‐NH₂ ( 26 ) showed significant permeation in the in vitro cell‐based human model of the BBB, suggesting an active mechanism of cell penetration.     

PRESSURIZED ELECTROOSMOTIC DEWATERING IN A FILTER CYCLE

This paper describes the role of pressurized electroosmotic dewatering (EOD) in a filter cycle. A laboratory-scale filter-press was used to filter a highly conductive silica suspension under constant pressure, followed by washing and mechanical precompression of the filter cake and finally by pressurized EOD at constant electric current. The influence of filter cycle parameters (filtration and washing pressure and duration, mechanical pressure, and electric field intensity) on the final cake dryness and energy consumption was studied. Electrodes of different materials, forms, and surfaces were used.

The optimal conditions of each filter cycle operation were found to minimize the energy consumption during EOD and maximize the cake dryness. With mechanical pressure and electric field intensity increasing, the total energy consumption increased, but the specific energy consumption (per kg of expressed water) decreased, and the final filter cake was dryer. The pressurized EOD also used less energy than thermal drying.