Reviews

THE IMPROVEMENT OF LONDON'S GREEN BELT — A SECOND REPORT (SC 860R) Green Belt Working Group, Standing Conference on London and South East Regional Planning

THE SCHOOL OUTDOOR RESOURCE AREA School Council Project Environment 1970-73 (Longmans 1974: Price £2.95) University of Newcastle Upon Tyne Director — R W Coleton, Deputy Director — R F Morgan

URBAN WASTELAND A report on land lying dormant in cities, towns and villages in Britain by Timothy Cantell 1977 56pp. CIVIC TRUST.     

A conceptual design for a space-based solar water heater

A solar water heater is proposed for use aboard manned spacecraft on extended missions such as space stations, lunar bases, or planetary exploration. A mathematical model for designing such a heater and predicting its performance is presented herein. The model uses solar thermal collectors, and accounts for realistic radiant energy incident on the collector as well as realistic demands for hot water. Theoretical development of the model, calculation schemes, and sample results (applicable to NASA's Space Station) are presented in this publication. The model is found to be very efficient and economic design tool considering the high expense of experimenting with scale models.     

Multiplexed p53 mutation detection by free-solution conjugate microchannel electrophoresis with polyamide drag-tags

We report a new, bioconjugate approach to performing highly multiplexed single-base extension (SBE) assays, which we demonstrate by genotyping a large panel of point mutants in exons 5-9 of the p53 gene. A series of monodisperse polyamide "drag-tags" was created using both chemical and biological synthesis and used to achieve the high-resolution separation of genotyping reaction products by microchannel electrophoresis without a polymeric sieving matrix. A highly multiplexed SBE reaction was performed in which 16 unique drag-tagged primers simultaneously probe 16 p53 gene loci, with an abbreviated thermal cycling protocol of only 9 min. The drag-tagged SBE products were rapidly separated by free-solution conjugate electrophoresis (FSCE) in both capillaries and microfluidic chips with genotyping accuracy in excess of 96%. The separation requires less than 70 s in a glass microfluidic chip, or about 20 min in a commercial capillary array sequencing instrument. Compared to gel electrophoresis, FSCE offers greater freedom in the design of SBE primers by essentially decoupling the length of the primer and the electrophoretic mobility of the genotyping products. FSCE also presents new possibilities for the facile implementation of SBE on integrated microfluidic electrophoresis devices for rapid, high-throughput genetic mutation detection or SNP scoring.     

Artesunate and dihydroartemisinin (DHA): unusual decomposition products formed under mild conditions and comments on the fitness of DHA as an antimalarial drug

Artesunate drug substance, for which a rectal capsule formulation is under development for the treatment of severe malaria, when heated at 100 degrees C for 39 h gives beta-artesunate, artesunate dimers, 9,10-anhydrodihydroartemisinin (glycal), a DHA beta-formate ester, and smaller amounts of other products that arise via intermediate formation of dihydroartemisinin (DHA) and subsequent thermal degradation. Solid DHA at 100 degrees C provides an epimeric mixture of a known peroxyhemiacetal, arising via ring opening to a hydroperoxide and re-closure, smaller amounts of a 3:1 mixture of epimers of a known tricarbonyl compound, and a single epimer of a new dicarbonyl compound. The latter arises via homolysis of the peroxide and an ensuing cascade of alpha-cleavage reactions which leads to loss of formic acid incorporating the C10 carbonyl group of DHA exposed by this 'unzipping' cascade. The tricarbonyl compound that arises via peroxide homolysis and extrusion of formic acid from a penultimate hydroxyformate ester incorporating C12 of the original DHA, is epimeric at the exocyclic 1'-aldehyde, and not in the cyclohexanone moiety. It is converted into the dicarbonyl compound by peroxide-induced deformylation. The dicarbonyl compound is not formed during anhydrous ferrous bromide mediated decomposition of DHA at room temperature, which provides the 1'-R epimer of the tricarbonyl compound as the dominant product; this equilibrates at room temperature to the 3:1 mixture of epimers of the tricarbonyl compound obtained from thermolysis. Each of artesunate and DHA decomposes readily under aqueous acidic conditions to provide significant amounts of the peroxyhemiacetal, which, like DHA, decomposes to the inert end product 2-deoxyartemisinin under acidic or basic conditions. DHA and the peroxyhemiacetal are the principal degradants in aged rectal capsule formulations of artesunate. TGA analysis and thermal degradation of DHA reveals a thermal lability which would pose a problem not only in relation to ICH stability testing guidelines, but in the use of DHA in fixed formulations currently under development. This thermolability coupled with the poor physicochemical properties and relative oral bioavailability of DHA suggests that it is inferior to artesunate in application as an antimalarial drug.     

Preparation of N-sulfonyl- and N-carbonyl-11-azaartemisinins with greatly enhanced thermal stabilities: in vitro antimalarial activities

As the clinically used artemisinins do not withstand the thermal stress testing required to evaluate shelf life for storage in tropical countries where malaria is prevalent, there is a need to develop thermally more robust artemisinin derivatives. Herein we describe the attachment of electron-withdrawing arene- and alkanesulfonyl and -carbonyl groups to the nitrogen atom of the readily accessible Ziffer 11-azaartemisinin to provide the corresponding N-sulfonyl- and -carbonylazaartemisinins. Two acylurea analogues were also prepared by treatment of the 11-azaartemisinin with arylisocyanates. Several of the N-sulfonylazaartemisinins have melting points above 200 degrees C and possess substantially greater thermal stabilities than the artemisinins in current clinical use, with the antimalarial activities of several of the arylsulfonyl derivatives being similar to that of artesunate against the drug-sensitive 3D7 clone of the NF54 isolate and the multidrug-resistant K1 strain of P. falciparum. The compounds possess relatively low cytotoxicities. The carbonyl derivatives are less crystalline than the N-sulfonyl derivatives, but are generally more active as antimalarials. The N-nitroarylcarbonyl and arylurea derivatives possess sub-ng ml(-1) activities. Although several of the azaartemisinins possess log P values below 3.5, the compounds have poor aqueous solubility (<1 mg L(-1) at pH 7). The greatly enhanced thermal stability of our artemisinins suggests that strategic incorporation of electron-withdrawing polar groups into both new artemisinin derivatives and totally synthetic trioxanes or trioxolanes may assist in the generation of practical new antimalarial drugs which will be stable to storage conditions in the field, while retaining favorable physicochemical properties.     

Molecular thermodynamics of LNA:LNA base pairs and the hyperstabilizing effect of 5′‐proximal LNA:DNA base pairs

Locked nucleic acids (LNAs) can greatly enhance duplex DNA stability, and are therefore creating opportunities to improve therapeutics, as well as PCR‐based disease and pathogen diagnostics. Realizing the full potential of LNAs will require better understanding of their contributions to duplex stability, and the ability to predict their hydridization thermodynamics. Melting thermodynamics data for a large set of diverse duplexes containing LNAs in one or both strands are presented. Those data reveal that LNAs, when present on both strands, can stabilize a duplex not only through direct interaction with their base‐pair partner, but also through nonlocal hyperstablization effects created by LNA:LNA base pairs and/or specific patterns of oppositely oriented LNA:DNA base pairs. The data are, therefore, used to extend a thermodynamic model previously developed in our lab to permit accurate prediction of melting temperatures for duplexes bearing LNA substitutions within both strands using a classic group‐contribution approach. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2711–2731, 2015     

Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild-type levels of virulence

The conserved family of fungal Ste20 p21-activated serine-threonine protein kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20 is involved in pheromone signalling, invasive growth, the hypertonic stress response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding protein required for polarized morphogenesis. We have cloned the STE20 homologue from the fungal pathogen Candida glabrata and have shown that it is present in a single copy in the genome. Translation of the nucleotide sequence predicts that C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine protein kinase domain, a binding site for G-protein beta subunits and a regulatory Rho-binding domain that enables the kinase to interact with Cdc42 and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58% predicted amino acid similarity to S. cerevisiae Ste20 and can complement both the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C. glabrata Ste20 is required for a fully functional hypertonic stress response and intact cell wall integrity pathway. C. glabrata Ste20 is not required for nitrogen starvation-induced filamentation. Survival analysis revealed that C. glabrata ste20 mutants, while still able to cause disease, are mildly attenuated for virulence compared to reconstituted STE20 cells.     

Parenting knowledge: Experiential and sociodemographic factors in European American mothers of young children.

Knowledge of child rearing and child development is relevant to parenting and the well-being of children. Using a sociodemographically heterogeneous sample of 268 European American mothers of 2-year-olds, we assessed the state of mothers' parenting knowledge; compared parenting knowledge in groups of mothers who varied in terms of parenthood and social status; and identified principal sources of mothers' parenting knowledge in terms of social factors, parenting supports, and formal classes. On the whole, European American mothers demonstrated fair but less than complete basic parenting knowledge; age, education, and rated helpfulness of written materials each uniquely contributed to mothers' knowledge. Adult mothers scored higher than adolescent mothers, and mothers improved in their knowledge of parenting from their first to their second child (and were stable across time). No differences were found between mothers of girls and boys, mothers who varied in employment status, or birth and adoptive mothers. The implications of variation in parenting knowledge and its sources for parenting education and clinical interactions with parents are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of green-colour-emitting pyrotechnics as a core for 3D temperature imaging sensors inside coal boilers

Efficiency in the control operation of the boilers for coal and coal with biomass can be further improved if the flue gas temperature distribution can be better characterized. This is very difficult in these harsh environmental systems, where spatially resolved measurements are nearly impossible with solid-state sensors. In this work, we evaluate the development of pyrotechnic compounds that would serve as the basis for a novel optical mapping of the temperature inside coal boilers. For this purpose, various green-colour-emitting pyrotechnics using BaCl₂ · 2H₂O and Ba(NO₃)₂ as the green light source were prepared, as this colour offers a distinct signal from the combustion-based background in the boiler. These pyrotechnics were characterized using thermogravimetric analysis (TGA) and X-ray diffraction (XRD) and tested using a flat-flame burner. Furthermore, the composition was varied to evaluate the effect of different metal fuels such as Sn, Co, and Mg, as well as various binders such as ethylcellulose, shellac, parlon, and PVC on green light emission. The emission intensity and the apparent ignition temperature were strongly dependent on the metal type, with Mg showing higher intensities. On the other hand, the effect of the binder showed that the ignition behaviour, emission intensity, and spectral purity were influenced by the nature and exothermicity of the binder. The addition of other potential green light-producing materials, such as boric acid, increased the intensity of emission by 17% for a BaCl₂ · 2H₂O-based composition. This study identified prospective compositions with intense and bright green-colour emissions that have high spectral purities.