DNA-binding preferences of bisantrene analogues: relevance to the sequence specificity of drug-mediated topoisomerase II poisoning

To elucidate structure-activity relationships for drugs that are able to poison or inhibit topoisomerase II, we investigated the thermodynamics and stereochemistry of the DNA binding of a number of anthracene derivatives bearing one or two 4, 5-dihydro-1H-imidazol-2-yl-hydrazone side chains (characteristic of bisantrene) at different positions of the planar aromatic system. An aza-bioisostere, which can be considered a bisantrene-amsacrine hybrid, was also tested. The affinity for nucleic acids in different sequence contexts was evaluated by spectroscopic techniques, using various experimental conditions. DNA-melting and DNase I footprinting experiments were also performed. The location and number of the otherwise identical side chains dramatically affected the affinity of the test compounds for the nucleic acid. In addition, the new compounds exhibited different DNA sequence preferences, depending on the locations of the dihydroimidazolyl-hydrazone groups, which indicates a major role for the side-chain position in generating specific contacts with the nucleic acid. Molecular modeling studies of the intercalative binding of the 1- or 9-substituted isomers to DNA fully supported the experimental data, because a substantially more favorable recognition of A-T steps, compared with G-C steps, was found for the 9-substituted derivative, whereas a much closer energy balance was found for the 1-substituted isomer. These results compare well with the alteration of base specificity found for the topoisomerase II-mediated DNA cleavage stimulated by the isomeric drugs. Therefore, DNA-binding specificity appears to represent an important determinant for the recognition of the topoisomerase-DNA cleavable complex by the drug, at least for poisons belonging to the amsacrine-bisantrene family.     

RNA tertiary structure mediation by adenosine platforms

The crystal structure of a group I intron domain reveals an unexpected motif that mediates both intra- and intermolecular interactions. At three separate locations in the 160-nucleotide domain, adjacent adenosines in the sequence lie side-by-side and form a pseudo-base pair within a helix. This adenosine platform opens the minor groove for base stacking or base pairing with nucleotides from a noncontiguous RNA strand. The platform motif has a distinctive chemical modification signature that may enable its detection in other structured RNAs. The ability of this motif to facilitate higher order folding provides one explanation for the abundance of adenosine residues in internal loops of many RNAs.     

Investigation of optical losses in photoelastic and ridge waveguides in GaAs-AlGaAs heterostructures

Two approaches have been used to fabricate stable photoelastic waveguides with planarized surfaces on GaAs-AlGaAs heterostructures. The first approach uses tensile Ni/sub 3/GaAs stressors formed by metal-semiconductor reactions. The second approach uses inert, refractory and compressive stressors, such as RF sputtered W and RF co-sputtered WNi films. For comparison purposes, ridge waveguides have also been fabricated using the same heterostructure by a dry etching technique. Optical losses of photoelastic waveguides, measured by Fabry-Perot (FP) method at a wavelength of 1.53 /spl mu/m, are comparable to or better than those of the ridge waveguides. Material loss appears to be the primary loss mechanism in both photoelastic and ridge waveguides. These results indicate that the photoelastic waveguide processing technique reported in this study is a promising alternative to commonly used dry etching techniques for planarization.     

Reaction of carboxylic acids on CeO2(111) and CeO2(100)

The reactions of HCOOH and CH₃COOH on CeO₂(111) and CeO₂(100) were studied using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS). The carboxylic acids were found to dissociate on both surfaces to form carboxylates. Adsorbed formates and acetates decomposed near 600 K to produce primarily the dehydration products CO and CH₂CO, respectively. This result is consistent with previous studies which have indicated that the ease of reduction of the oxide is the primary factor in determining the selectivity for dehydration versus dehydrogenation during carboxylate decomposition. In addition to CO and CO₂, small amounts of formaldehyde were produced during formate decomposition on both CeO₂(111) and CeO₂(100). In contrast, acetone was observed as a product during acetate decomposition only on the CeO₂(111) surface.     

Data collection: evaluation of a pilot model

The overall purpose of this study was to explore nurses' feelings about the applicability and adequacy of a pilot model of nursing assessment (PMNA) developed for coronary care units (CCU) in order to obtain data that could help in establishing a definitive model. The evaluation, performed by 11 CCU nurses, showed that they considered the development and implementation of PMNA as valuable, and that its design was adequate for interviewing cardiac patients. These results will be employed in the elaboration of a definitive model of nursing assessment.     

Measurement and prediction of pressure drop in two-phase flow

Experimental data for air–water two-phase co-current flow in two different pipe diameters were used to test the prediction of pressure drop by a number of existing theories and correlations. Several models are shown to be useful for prediction, particularly with the stratified regimes which have proved difficult to handle in the past. The model suggested by Olujic proved to be of particular value.     

The use of 15N-labeled dietary proteins for determining true ileal amino acid digestibilities is limited by their rapid recycling in the endogenous secretions of pigs

We assessed the use of 15N-labeled dietary proteins as a possible tool for the determination of the true ileal amino acid (AA) digestibility in pigs. The first experiment was designed to study the dietary N excretion pattern at the ileum subsequent to the ingestion of a single 15N-labeled meal. In a second experiment, we compared ileal endogenous AA outputs and true AA digestibility estimates obtained in pigs ingesting 15N-labeled dietary proteins in a single meal vs. intravenous infusion of [15N]leucine for 10 d during the ingestion of a pea-based diet and a protein-free starch diet. The proportion of endogenous N found in the ileal digesta differed when the label was delivered orally (50%) vs. intravenously (72%) and changed with time. As a consequence, the true ileal AA digestibilities measured with labeled diets were lower. A third experiment demonstrated that this was due to the rapid recycling of labeled dietary N in endogenous moieties, because 15N was found in blood within 10 min of consuming the labeled meal, within 50 min of consumption in pancreatic enzymes, 90 min in bile and 4 h in ileal mucins. We conclude that the use of 15N-labeled meals for determination of true ileal AA digestibilities is limited by the fast recycling of dietary N in endogenous secretions following a single 15N-labeled meal. The accuracy of results will depend on meaningful estimates of AA flow during a limited period and accurate estimates of 15N in AA.     

Sintering high performance semicrystalline polymeric powders

Poly(ether ether ketone) (PEEK) is high performance semicrystalline thermoplastic with a glass transition temperature of 143°C. The melting point (Tm) is quoted as 334°C. Because of its high thermal transitions, PEEK, requires high temperatures for processing, at least 370–400°C. It has been determined that under the recommended processing conditions PEEK can undergo branching and eventually crosslinks. An alternative to melt processing PEEK is to apply the powder metallurgy technique of sintering. This involves cold (room temperature) compaction of the polymeric powder, followed by pressure free sintering of the resultant green body. We have reported a process for preparing submicron PEEK particles, and the focus here is on the free sintering of these particles with emphsis on the effects of particle size, sintering temperature, and compaction pressure. The data is evaluated using the two particle model developed by Frenkel as well as the crack healing theory developed by Wool.     

Isothermic growth of one spherulite around circular obstacles in a polypropylene foil

Growth of one spherulite within a thin foil of polypropylene around one circular obstacle or around combinations of circular obstacles is investigated. For each obstacle there exists a region of shadow, seen from the nucleus of the spherulite, which influences the growth of the spherulite. Within any region of shadow the growth fronts are evolvents of the obstacle's boundary, because the spherulite grows isotropically. When two growth fronts belonging to one spherulite meet each other inside the shadow, an intrinsic grain boundary is formed for each obstacle. Additionally, growth of one spherulite around a rectangular obstacle and a spherical obstacle is investigated.