Binding of 2-azaanthraquinone derivatives to DNA and their interference with the activity of DNA topoisomerases in vitro

We have investigated the binding ability to DNA of compounds belonging to the 2-azaanthraquinone-type structure and have examined the effect on the activity of DNA gyrase as well as on mammalian topoisomerases in vitro. Using different biophysical techniques it was found that one of these ligands, 9-((2-dimethylamino)ethyl)amino)-6-hydroxy-7-methoxy-5, 10-dihydroxybenzo[g]isoquinoline-5,10-dione (TPL-I), is an intercalating DNA binding agent, whereas the parent compound tolypocladin (TPL) and a derivative (TPL-II) showed almost no similar affinity to DNA. CD measurements demonstrated a significant and selective binding tendency of TPL-I to alternating purine/pyrimidine sequences with some preference for poly(dA-dT). poly(dA-dT). Tm values were increased of the ligand complex with the alternating AT-containing duplex polymer. The binding to various DNAs was characterized by CD and visible absorption spectral changes. From the latter, different binding constants of 6.2 x 10(5) and 1.5 x 10(5) M-1 were obtained for poly(dA-dT).poly(dA-dT) and poly(dA). poly(dT), respectively. Sedimentation measurements with supercoiled pBR322 plasmid DNA clearly indicated an intercalative binding mechanism associated with an unwinding angle of about 18 degrees. These results suggest that the intercalative binding of TPL-I is promoted by the 2-(dimethylamino)ethylamino group substituted on carbon 9 of the anthraquinone system. The cytotoxic compound TPL-I, but not TPL or TPL-II, effectively inhibited the DNA supercoiling reaction of DNA gyrase and the activity of mammalian topoisomerases I and II as measured by the relaxation assay. TPL-I affects the cleavage reaction of topoisomerases on a single site located in alternating purine-pyrimidine sequence regions. The inhibitory potency of TPL-I can be ascribed to a blocking of cleavage sites on the DNA substrate, which correlates with the sequence preference of the ligand.     

Energy expenditure of a noncontact boxing training session compared with submaximal treadmill running

The aim of this study was to determine the energy expenditure of a 1-h noncontact boxing training session and to compare these results with the energy expenditure of a more conventional recreational activity such as running. Eight healthy males, accustomed to noncontact boxing training, were recruited for the study. Subjects underwent three tests: (i) a boxing training session in the laboratory during which energy expenditure was measured continuously using indirect calorimetry (BOXL), (ii) a boxing training session in a boxing studio during which heart rate was measured continuously (BOXS), and (iii) an incremental running test on the treadmill during which energy expenditure was measured continuously. The energy expenditure during 60 min of BOXL ranged between 2519 and 3079 kJ (2821 +/- 190 kJ). Seven of the 8 subjects had higher heart rates during BOXL compared with those during BOXS, suggesting that the subjects exercised at a slightly higher intensity during BOXL, possibly because of the "one on one" supervision. A typical boxing training session lasting 60 min causes a person to expend 2821 +/- 190 kJ x h(-1), the same amount of energy as someone running about 9 km in 60 min on the treadmill.     

Na2SO4- and NaCl-Induced hot corrosion of six nickel-base superalloys

The short-time hot-corrosion behavior of six industrial nickel-base superalloys was investigated with static deposits of Na₂SO₄ or NaCl or both in still air. The oxidation kinetics and scale morphologies were measured with traditional laboratory techniques-thermobalance, metallography, electron microprobe, and x-ray analyses. Susceptibility to hot corrosion was found to be correlated to the type of scale produced during simple oxidation. Alloys forming an A1₂O₃ scale were found to be susceptible to Na₂SO₄ deposits, independent of their chromium content. The quantity of Na₂SO₄ deposit dictated the nature of the attack and, under certain conditions, the refractory element alloy additions appeared to play an essential role. Alloys containing Cr₂O₃ or TiO₂ in the simple oxidation scale proved to be sensitive to NaCl attack. Again, the severity of the attack within the susceptible alloy group was not related to the chromium or titanium content. Although less intensive than the Na₂SO₄ -induced hot corrosion, NaCl contaminations provoked extensive spalling. All of the hotcorrosion types encountered in this study were interpreted in the light of existing theories.Supported by the Délégation Générale à la Recherche Scientifique et Technique.     

Spiral Tunneling Cracks Induced by Environmental Stress Cracking in LaRC™-TPI Adhesives

Some currently-available formulations of LaRC?-TPI, a thermoplastic polyimide originally developed at NASA-Langley, were found to be highly susceptible to environmental stress cracking when exposed to solvents such as acetone, toluene, diglyme and methyl ethyl ketone. The combination of stress and solvent led to rapid cracking in films and adhesive layers of this material system. Residual cool-down stresses induced when the LaRC-TPI is used as an adhesive or coating led, in the presence of a solvent, to dense “mud crack” patterns which relieve a portion of the stored energy. Because these through-the-thickness cracks are not able to relieve the stored energy in the vicinity of the adherends, additional fractures in the form of curious spiral tunnel cracks initiated and grew inward within each adhesive fragment. Micrographs of the spiral fractures are given, along with a qualitative explanation for the failure process as observed in adhesives and coatings.     

Effect of brighteners on hydrogen evolution during zinc electroplating from zincate electrolytes

Hydrogen evolution during zinc electrodeposition on a steel substrate from zincate electrolytes containing different additives was studied using various experimental techniques.The hydrogen evolution reaction is limited by the electron transfer step. Hydrogen evolution is most intensive during the first seconds from the beginning of electrodeposition due to the lower overpotential of hydrogen on steel as compared with that on zinc. The evolved hydrogen is dissipated in three ways. Most is dissipated to the atmosphere via gas bubbles at a constant rate. Some is dispersed in the electrolyte some diffuses into the steel substrate, predominantly at the commencement of deposition. The additives affect both the total amount of evolved hydrogen and its distribution. The highest amount of hydrogen is evolved in the presence of the anisaldehyde bisulphite containing composite additive. The highest amount of hydrogen included in the substrate and remaining in the electrolyte corresponds to the use of the Na–N-benzylnicotinate containing additive. In this case blistering is observed.     

An Investigation of Error Sources in Computational Fluid Dynamics Modelling of a Co-current Spray Dryer

The paper is focused on identifying error sources in computational fluid dynamics(CFD) predictions of a spray drying process. Seven groups of drying and atomisation parameters were selected for analysis and 13 simulation trials were performed. The theoretical results were compared with experimental data and sensitivity of the simulation results to the analysed factors was determined. The following parameters affecting the accuracy of CFD spray modelling were found: gas turbulence model, particle dispersion, atomising air, initial parameters of atomisation and heat losses to the environment. A major difference in the errors committed during modelling of spray drying process for fine and coarse sprays was observed.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

Application of extended quadrature method of moments for simulation of bubbly flow and mass transfer in gas‐liquid stirred tanks

In the present paper, two gas‐liquid stirred tanks, one agitated by a radial impeller and another by an axial impeller, are modelled using the open‐source computational fluid dynamic (CFD) package OpenFOAM (open source field operation and manipulation). The combined effect of the bubble break‐up and coalescence in the tank is considered by a population balance model (PBM) called extended quadrature method of moments (EQMOM). The three‐dimensional simulation is made using a multiple reference frame (MRF), a well‐established method for the modelling of mixers. Dispersed gas and bubble dynamics in the turbulent flow are modelled using the Eulerian‐Eulerian approach (E‐E) with mixture k‐epsilon turbulent model and the modified Tomiyama drag coefficient for the momentum exchange. The model is developed to predict the spatial distribution of gas phase fraction, Sauter mean bubble diameter (), number density function (NDF), dissolved oxygen (DO) evolution, and flow structure. The numerical results are compared with experimental data and a fair agreement is achieved. The results of the axial impeller are discussed based on four impeller rotational speeds with different volumetric mass transfer coefficients.     

Synthesis of ‘ready-to-adsorb’ polymeric nanoshells for magnetic iron oxide nanoparticles via atom transfer radical polymerization

Polymer-magnetite nanoparticle complexes that respond to both magnetic fields and to temperature have been demonstrated. Novel alkyl halide-functional bis(diethylphosphonate) esters were prepared and utilized as initiators for polymerizing N-isopropylacrylamide by controlled atom transfer radical polymerization. The phosphonate esters were removed after polymerization to afford poly(N-isopropylacrylamide) with a bis(phosphonic acid) moiety precisely placed at one terminus. The bis(phosphonic acid) endgroups were adsorbed onto magnetite nanoparticles to yield nanoscale complexes that were stable against any polymer desorption and that were colloidally-stable in physiological media. Thus, the bis(phosphonate) endgroup provides a robust anchoring moiety onto the magnetite. Hydrodynamic sizes of the complexes were predicted with a density distribution model and using the measured sizes of the magnetite cores. Good agreement between the measured and predicted hydrodynamic sizes suggested that the complexes were primarily discrete, non-agglomerated nanoparticles. The complexes exhibited thermosensitive aggregation behavior near the lower critical solution temperature of the poly(N-isopropylacrylamide) component.     

Investigation of γ-Linolenic Acid and Stearidonic Acid Biosynthesis During a Life Cycle of <Emphasis Type="Italic">Borago officinalis</Emphasis> L.

This study investigated the levels of γ-linolenic (GLA, 18:3n-6) and stearidonic acid (SDA, 18:4n-3) in various parts of the borage plant (Borago officinalis L.) to elucidate Δ6-desaturase activity. Lipid class and fatty acid (FA) composition during germination of the seeds and FA composition of various borage parts were determined as well as FA compositions of neutral lipids (NL), polar lipids (PL), glycolipids (GL) and monogalactosyl diacylglycerols (MGDG) of borage leaves. When seeds were germinated for 12 days in the dark then exposed to light for 8 h, an overall decrease in oil content was seen with a significant increase in PL from 0.2 to 39.1%. An increase in SDA (from 0.2 to 0.6 g/100 g oil) indicated minor FA synthesis during germination and therefore, Δ6-desaturase activity with the most marked increase after light exposure. The FA compositions of developing and mature seeds were similar, suggesting oil/FA synthesis takes place at the initial stage of seed development. Among all the borage parts, the leaves had the highest amounts of α-linolenic acid (ALA, 18:3n-3) (36.2%), indicating Δ15-desaturase activity, and SDA (25.2%), indicating Δ6-desaturase activity. In leaves, the GL and especially, MGDG fractions had the highest amounts of SDA (31.8 and 39.8%, respectively), indicating that Δ6-desaturase is most active in chloroplasts. Leaves and developing seeds appear to be the major sources of Δ6-desaturase in borage, associated with different organelles in the different tissues.