Current Understanding of Structure–Processing–Property Relationships in BaTiO3–Bi(M)O3 Dielectrics

As part of a continued push for high permittivity dielectrics suitable for use at elevated operating temperatures and/or large electric fields, modifications of BaTiO₃ with Bi(M)O₃, where M represents a net‐trivalent B‐site occupied by one or more species, have received a great deal of recent attention. Materials in this composition family exhibit weakly coupled relaxor behavior that is not only remarkably stable at high temperatures and under large electric fields, but is also quite similar across various identities of M. Moderate levels of Bi content (as much as 50 mol%) appear to be crucial to the stability of the dielectric response. In addition, the presence of significant Bi reduces the processing temperatures required for densification and increases the required oxygen content in processing atmospheres relative to traditional X7R‐type BaTiO₃‐based dielectrics. Although detailed understanding of the structure–processing–property relationships in this class of materials is still in its infancy, this article reviews the current state of understanding of the mechanisms underlying the high and stable values of both relative permittivity and resistivity that are characteristic of BaTiO₃‐Bi(M)O₃ dielectrics as well as the processing challenges and opportunities associated with these materials.     

Host Plant Volatiles Synergize Response to Sex Pheromone in Codling Moth, Cydia pomonella

Plant volatile compounds synergize attraction of codling moth males Cydia pomonella to sex pheromone (E,E)-8,10-dodecadien-1-ol (codlemone). Several apple volatiles, known to elicit a strong antennal response, were tested in a wind tunnel. Two-component blends of 1 pg/min codlemone and 100 pg/min of either racemic linalool, (E)-beta-farnesene, or (Z)-3-hexen-1-ol attracted significantly more males to the source than codlemone alone (60, 58, 56, and 37%, respectively). In comparison, a blend of codlemone and a known pheromone synergist, dodecanol, attracted 56% of the males tested. Blends of pheromone and plant volatiles in a 1:100 ratio attracted more males than 1:1 or 1:10,000 blends. Adding two or four of the most active plant compounds to codlemone did not enhance attraction over blends of codlemone plus single-plant compounds. Of the test compounds, only farnesol was attractive by itself; at a release rate of 10,000 pg/min, 16% of the males arrived at the source. However, attraction to a 1:10,000 blend of codlemone and farnesol (42%) was not significantly different from attraction to codlemone alone (37%). In contrast, a codlemone mimic, (E)-10-dodecadien-1-ol, which attracted 2% males by itself, had a strong antagonistic effect when blended in a 1:10,000 ratio with codlemone.     

La0.6Sr0.4Co0.2Fe0.8O3-δ nanofiber cathode for intermediate-temperature solid oxide fuel cells by water-based sol-gel electrospinning: Synthesis and electrochemical behaviour

Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La_0.6Sr_0.4Co_0.2Fe_0.8O_3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce_0.9Gd_0.1O_1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance R_p is 1.0 Ω cm². Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h.     

A comprehensive study of the loss of enzyme activity in a continuous membrane reactor – application to starch hydrolysis

Loss of enzyme activity is a problem associated with enzymatic reactions in continuous recycled membrane reactors (CRMR). It may result from catalyst leakage and also enzyme denaturation due to the effects of pH, temperature, shear effects or adsorption/deposit on membrane. In this study, the relative importance of these various factors has been assessed in order to reduce their adverse effects on starch hydrolysis in a CRMR. The effects of temperature and denaturation by adsorption/deposit on membrane were the most limiting phenomena. Reducing the temperature to overcome thermal denaturation was not a practical solution since this increases viscosity and thereby decreases permeate flux and reactor performance. Insofar that adsorption/deposit of enzymes on the membrane is directly linked to membrane fouling, back‐flushing or regularly purging retentate should reduce this phenomenon by lowering accumulation of high molecular weight products. © 2001 Society of Chemical Industry     

Thioether Analogues of Disulfide‐Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis,Dimerisation and Consequences for Receptor Activation

Cyclic peptides containing redox‐stable thioether bridges might provide a useful alternative to disulfide‐bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16‐mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL‐R2). Upon covalent oligomerisation, the disulfide‐bridged peptide has previously shown similar behaviour to that of TNF‐related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5‐binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5‐mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models.     

Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites

Ferrociphenols have been found to have high antiproliferative activity against estrogen‐independent breast cancer cells. The rat and human liver microsome‐mediated metabolism of three compounds of the ferrocifen ( FC ) family, 1,1‐bis(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC1 ), 1‐(4‐hydroxyphenyl)‐1‐(phenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC2 ), and 1‐[4‐(3‐dimethylaminopropoxy)phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC3 ), was studied. Three main metabolite classes were identified: quinone methides ( QM s) deriving from two‐electron oxidation of FC s, cyclic indene products ( CP s) deriving from acid‐catalyzed cyclization of QM s, and allylic alcohols ( AA s) deriving from hydroxylation of FC s. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N‐benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450‐dependent oxidation of the phenol function and hydroxylation of the allylic CH₂ group of FC s leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA‐MB‐231 hormone‐independent breast cancer cells.     

Dialysis and gel filtration of isolated low density lipoproteins do not cause a significant loss of low density lipoprotein tocopherol and carotenoid concentration

The resistance of isolated low density lipoprotein (LDL) to copper-initiated oxidation is often used as a measure of effectiveness of an antioxidant intervention. Prior to oxidation excess salt and EDTA are removed via dialysis or gel filtration of the LDL sample. However, there is concern over whether the antioxidant content of dialyzed or gel-filtered LDL is truly representative of native LDL extracted from a blood sample. Previously, the experiments done after the storage of native and dialyzed LDL at −80°C showed that the dialysis step can cause a loss of up to 60% in the tocopherol and carotenoid content of LDL. In the present study, a comparison of the micronutrient concentration in freshly prepared dialyzed and native LDL from 35 subjects showed that after the correction for cholesterol, only lycopene (13%, P<0.001) and to a lesser extent α-carotene (8%, P<0.02) were significantly decreased, and the absolute fall in concentration was far smaller than previously reported. Other experiments done with smaller numbers of samples suggested that there were minimal micronutrient losses following gel filtration and that it was important to include 10 μmol/L EDTA in the dialysis and elution buffer; otherwise micronutrient losses did occur. In summary, immediate dialysis of freshly isolated LDL in the presence of 10 μmol/L. EDTA does not cause any major loss in the concentration of tocopherol and most carotenoids.     

Transformation of Free and Dipeptide‐Bound Glycated Amino Acids by Two Strains of Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae transforms branched‐chain and aromatic amino acids into higher alcohols in the Ehrlich pathway. During microbiological culturing and industrial fermentations, this yeast is confronted with amino acids modified by reducing sugars in the Maillard reaction (glycation). In order to gain some preliminary insight into the physiological “handling” of glycated amino acids by yeasts, individual Maillard reaction products (MRPs: fructosyllysine, carboxymethyllysine, pyrraline, formyline, maltosine, methylglyoxal‐derived hydroimidazolone) were administered to two strains of S. cerevisiae in a rich medium. Only formyline was converted into the corresponding α‐hydroxy acid, to a small extent (10 %). Dipeptide‐bound pyrraline and maltosine were removed from the medium with concomitant emergence of several metabolites. Pyrraline was mainly converted into the corresponding Ehrlich alcohol (20–60 %) and maltosine into the corresponding α‐hydroxy acid (40–60 %). Five specific metabolites of glycated amino acids were synthesized and characterized. We show for the first time that S. cerevisiae can use glycated amino acids as a nitrogen source and transform them into new metabolites, provided that the substances can be transported across the cell membrane.     

Structure–Activity Relationships of Benzenesulfonamide‐Based Inhibitors towards Carbonic Anhydrase Isoform Specificity

Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease‐implicated CAs should minimally affect the ubiquitously expressed isoforms, including CA I and II, to improve directed distribution of the inhibitors to the cancer‐associated isoforms and reduce side effects. Four benzenesulfonamide‐based inhibitors were synthesized by using the tail approach and displayed nanomolar affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX mimic and CA II are presented. Further in silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contributed to or hindered their binding interactions. These structural studies demonstrated that active‐site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors, whereas the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed that the energetic penalties of the inhibitor conformations were negligible compared to the gains from active‐site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors.