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We present a simple liquid-assisted processing (LAP) method, to be used in situ during pulsed laser deposition growth to give both rapid growth rates (50 Hz deposition leading to >250 nm min���1 with a single plume) and strong pinning (improved ��5���10 at 30 K and below, over plain standard YBCO films grown at similar rates). Achieving these two important features simultaneously has been a serious bottleneck to date and yet for applications, it is critical to overcome it. The new LAP method uses a non-stoichiometric target composition, giving rise to a small volume fraction of liquid phase during film growth. LAP enhances the kinetics of the film growth so that good crystalline perfection can be achieved at up to 60�� faster growth rates than normal, while also enabling artificial pinning centres to be self-assembled into fine nanocolumns. In addition, LAP allows for RE mixing (80% of Y with 20% of Yb, Sm, or Yb + Sm), creating effective point-like disorder pinning centres within the rare earth barium cuprate lattice. Overall, LAP is a simple method for use in pulsed laser deposition, and it can also be adopted by other in situ physical or vapour deposition methods (i.e. MOCVD, evaporation, etc) to significantly enhance both growth rate and performance., Grant from SuNAM Co. Ltd. Henry Royce Institute Equipment Grant: EP/P024947/1

A number of phenanthrolines and benzoquinolines were examined for their ability to activate epithelial chloride secretion by measuring short circuit current (SCC) using the mouse colon epithelium. 1,10 phenanthroline stimulated electrogenic chloride secretion with an EC50 of 612±10 μ and a Hill slope of 4.9±0.3. A similar pharmacology was demonstrated by both 1,7 and 4,7 phenanthrolines, 7,8 benzoquinoline and phenanthridine. Evidence that the increase in SCC caused by 1,10 phenanthroline was due to chloride secretion is based upon (a) inhibition of the current by furosemide, (b) failure of cystic fibrosis (CF) colons to respond and (c) an associated net flux of 36Cl−. 1,10 Phenanthroline affected neither the generation of cyclic AMP or the concentration of intracellular Ca2+ in colonic epithelial cells. 1,10 phenanthroline affected the chloride conductance of the apical membrane, as shown by an increase in chloride current in ‘apical membrane only' preparations in the presence of an apical to basolateral chloride gradient. The increase in chloride current was inhibited by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and was not present in CF colons. Additionally, 1,10 phenanthroline activated basolateral K+ channels, both Ca2+- and cyclic AMP-sensitive channels, as shown by inhibitor studies with charybdotoxin (ChTX) and XE991, and after the apical membrane was permeabilized with nystatin. The phenanthrolines and benzoquinolines described here, with dual actions affecting CFTR and basolateral K+ channels, may constitute useful lead compounds for adjunct therapy in CF. Keywords: CFTR, cystic fibrosis, chloride channel openers, phenanthrolines, 7,8 benzoquinoline, phenanthridine, potassium channels, cyclic AMP, intracellular Ca2+ Introduction Increased interest in agents affecting epithelial chloride channels arose after it was shown that the cystic fibrosis transmembrane conductance regulator (CFTR) is also a chloride channel in many epithelial membranes (Anderson et al., 1991). Not only have blockers of CFTR been described but considerable interest has also focused on CFTR chloride channel openers (Schultz et al., 1999). The most common mutation in cystic fibrosis (CF) is ΔF508, in which phenylalanine is absent from position 508. This mutant protein (ΔF508CFTR) can function as a chloride channel (Drumm et al., 1991), however only a minute fraction of this protein is transported to the apical domain of epithelial cells (Ward & Kopito, 1994). Instead the quality control mechanisms of the cell cause the mutant protein to be degraded in the proteasome. Therefore attempts are being made to increase the delivery of ΔF508 CFTR to the membrane (Brodsky, 2001; Fischer et al., 2001; Fuller & Cuthbert, 2000). Thus agents which open CFTR channels are of interest, particularly so if they also activate ΔF508 CFTR. The present classes of CFTR openers are as follows; phosphatase inhibitors (Becq et al., 1998), xanthines, particularly CPX (Guay-Broder et al., 1995), benzimidazolones such as EBIO (Devor et al., 1996; Cuthbert et al., 1999), flavones, for example genistein (Illek et al., 1995), benzoxazolones like chlorzoxazone (Singh et al., 2000) and finally the MPB compounds described by Becq et al. (1999). The purpose of this study was to further investigate the actions of 1,10 phenanthroline on chloride secretion in the mouse colon following the observations made by Duszyk et al. (1999) that 1,10 phenanthroline, a powerful inhibitor of matrix metalloproteases (MMPs) activated a chloride conductance, measured as whole cell current, in human airway epithelial cells, Calu-3. No effect was found in airway cells lacking CFTR, namely A549 cells. Furthermore, an antibody to MMP2 caused a similar effect in Calu-3 cells as did 1,10 phenanthroline, suggesting metalloproteinase inhibition was responsible. A further aim was to explore structure activity relations in the phenanthroline isomers and to ask if both heterocyclic nitrogens in the tricyclic aromatic molecules were necessary for the effect. From various experimental approaches we conclude that the phenanthrolines and related structures constitute a new class of agents that stimulate chloride secretion.

Colored paper from magazines and newsprint was fed as 23% of a ration to sheep for 124 days. Among 44 elements determined in the paper and selected sheep tissues, marked accumulation of lead in animal organs was found reaching 22 ppm in bone. Barium and bromine was higher in kidney and fluorine was higher in bone of sheep fed the paper vs. the control ration. Histological examination of animal tissue revealed no apparent lesions which could be attributed to consumption of the paper diet. The sheep on the paper ration consumed more and gained weight at a faster rate than the control animals. The paper rations showed a higher in vivo digestibility than the control diet. 31 references.