Effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the antibiotic susceptibility of clinical bacterial isolates

This study aimed to determine the effect of sub-lethal challenge with Photodynamic Antimicrobial Chemotherapy (PACT) on the susceptibility of clinical Staphylococcus aureus and Pseudomonas aeruginosa isolates to both PACT and a range of antibiotics used in the treatment of infection caused by these bacteria. Clinical S. aureus and P. aeruginosa isolates were exposed to sub-lethal PACT with meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) and methylene blue (MB) over a 72 h period. After exposure, susceptibility of surviving organisms to a range of antibiotics was determined and compared with the susceptibility of an untreated control. Surviving bacteria were also exposed to previously lethal photosensitizer-light combinations, to determine if susceptibility to PACT was affected by sub-lethal exposure. Exposure to sub-lethal PACT did not decrease susceptibility to antibiotics with the minimum inhibitory concentrations for 95% and 100% of P. aeruginosa and S. aureus isolates, respectively, within two doubling dilutions of the MIC of the untreated control. Similarly, habituation with sub-lethal PACT did not reduce susceptibility of P. aeruginosa isolates to PACT levels previously determined as lethal. A reduction in susceptibility to PACT following habituation was apparent for two S. aureus isolates with MB and for 1 S. aureus isolate with IMP. However, for two of these three isolates, the log reduction for habituated cells was still greater than 4 log(10). PACT remains an attractive potential treatment for infection caused by these bacteria. (C) 2010 Elsevier B.V. All rights reserved.

Synthesis of the alkaloid homaline in ( ) and natural (S,S)-(-) forms, using amination and transamidative ring expansion in liquid ammonia.

Crombie, Leslie; Haigh, David; Jones, Raymond C. F.; Mat-Zin, A.Rasid. Dep. Chem., Univ. Nottingham, Nottingham, UK. Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1993), (17), 2047-54. CODEN: JCPRB4 ISSN: 0300-922X. Journal written in English. CAN 120:164608 AN 1994:164608 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract The alkaloid homaline I was prepd. in (?) and natural (S,S)-(-) forms. Linking of 2-azacyclooctanone units either directly or successively using 1,4-dihalogenobutanes or 1,4-dihalogenobut-2-ynes is examd. (?)-5-Methyl-4-phenyl-1,5-diazacyclooctan-2-one is first made by a 2,2'-dithiodipyridine/triphenylphosphine-mediated cyclization, and then by amination and transamidative ring expansion from N-(3-chloropropyl)-4-phenylazetidin-2-one in liq. ammonia, followed by N-methylation. Coupling through a 1,4-dihalogenobutane of either the N-methylated azalactam, or the unmethylated azalactam followed by methylation, gave homaline in (?) and meso forms. (R)-(-)-phenylglycine was converted via (S)-?-phenyl-?-alanine into an (S)-?-lactam which was then alkylated with 1-bromo-3-chloropropane, and aminated and ring expanded in liq. ammonia. Coupling of the homochiral azalactam (2 mol) so formed with 1,4-dibromobutane, followed by N-methylation, gave (S,S)-(-)-homaline identical with the natural material.

Synthesis and Reactions of Enantiopure Substituted Benzene cis-Hexahydro-1,2-diols

Enantiopure cis-dihydro-1,2-diol metabolites, obtained from toluene dioxygenase-catalysed cis-dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis-hexahydro-12-diol derivatives by catalytic hydrogenation via their cis-tetrahydro-1,2-diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis-dihydro-1,2-diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis-hexahydro-1,2-diol products have been unequivocally established by X-ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis-hexahydro-1,2-diol diastereoisomers, to desymmetrise a meso-cis-hexahydro-1,2-diol and to synthesise 2-substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.

Atomic ordering in nano-layered FePt: Multiscale Monte Carlo simulation

Nano- and meso-scale simulation of chemical ordering kinetics in nano-layered L1(0)-AB binary intermetallics was performed. In the nano- (atomistic) scale Monte Carlo (MC) technique with vacancy mechanism of atomic migration implemented with diverse models for the system energetics was used. The meso-scale microstructure evolution was, in turn, simulated by means of a MC procedure applied to a system built of meso-scale voxels ordered in particular L1(0) variants. The voxels were free to change the L1(0) variant and interacted with antiphase-boundary energies evaluated within the nano-scale simulations. The study addressed FePt thin layers considered as a material for ultra-high-density magnetic storage media and revealed metastability of the L1(0) c-variant superstructure with monoatomic planes parallel to the (001)-oriented layer surface and off-plane easy magnetization. The layers, originally perfectly ordered in the c-variant, showed discontinuous precipitation of a- and b-L1(0)-variant domains running in parallel with homogeneous disordering (i.e. generation of antisite defects). The domains nucleated heterogeneously on the free monoatomic Fe surface of the layer, grew inwards its volume and relaxed towards an equilibrium microstructure of the system. Two

Scaling of Superdomain Bands in Ferroelectric Dots

Bundles of 90° stripe domains have been observed to form into distinct groups, or bands, in mesoscale BaTiO3 single crystal dots. Vector piezoresponse force microscopy (PFM) shows that each band region, when considered as a single entity, possesses a resolved polarization that lies approximately along the pseudocubic direction; antiparallel alignment of this resultant polarization in adjacent bands means that these regions can be considered as 180° “superdomains.” For dots with sidewall dimensions below ~2 microns, Landau–Kittel like scaling in the width of these superdomains was observed, strongly suggesting that they form in response to lateral depolarizing fields. In larger dot structures, scaling laws break down. We have rationalized these observations by considering changes in the driving force for the adoption of equilibrium superdomain periodicities implied by Landau–Kittel-free energy models; we conclude that the formation of ordered bands of superdomains is a uniquely meso/nanoscale phenomenon. We also note that the superdomain bands found by PFM imaging in air contrast with the quadrant arrangements seen previously by Schilling et al. (Nano Lett., 9, 3359 (2009)) through transmission electron microscopy imaging in vacuum. The importance of the exact nature of the boundary conditions in determining the domain patterns that spontaneously form in nanostructures is therefore clearly implied.

SURFACE-ENHANCED RAMAN-SCATTERING STUDIES OF METALLOPORPHYRINS ON SILVER SOLS, MELLFS, AND ELECTRODES - EVIDENCE FOR REVERSIBLE PHOTOINDUCED DEMETALATION OF A SILVER(II) PORPHYRIN

A series of metalloporphyrins of the type M(TMPyP) (where M = Ag(II), Zn(II), Cu(II) and TMPyP = meso-tetrakis(4-N-methylpyridyl)porphyrin) have been investigated in solution and on the surface of silver sols, electrodes, and MELLFs (metal liquidlike films). Similar spectra were recorded on all three surfaces but significant differences in detailed behavior were found. In particular, a novel, reversible, and rapid photoinduced demetalation reaction has been observed for the AgII(TMPyP)/MELLF system. An apparently similar demetalation reaction for the same metalloporphyrin was observed on Ag electrodes but this reversed at a very much slower rate. No demetalation of Ag(II)(TMPyP) was observed with Ag sols nor with any of the other metalloporphyrins at any of the surfaces investigated. The implications of the findings in relation to the nature of the MELLF environment are briefly considered.

The typology of Irish hard rock aquifers based on an integrated hydrogeological and geophysical approach

Groundwater flow in hard-rock aquifers is strongly controlled by the characteristics and distribution of structural heterogeneity. A methodology for catchment-scale characterisation is presented, based on the integration of complementary, multi-scale hydrogeological, geophysical and geological approaches. This was applied to three contrasting catchments underlain by metamorphic rocks in the northern parts of Ireland (Republic of Ireland and Northern Ireland, UK). Cross-validated surface and borehole geophysical investigations confirm the discontinuous overburden, lithological compartmentalisation of the bedrock and important spatial variations of the weathered bedrock profiles at macro-scale. Fracture analysis suggests that the recent (Alpine) tectonic fabric exerts strong control on the internal aquifer structure at meso-scale, which is likely to impact on the anisotropy of aquifer properties. The combination of the interpretation of depth-specific hydraulic-test data with the structural information provided by geophysical tests allows characterisation of the hydrodynamic properties of the identified aquifer units. Regionally, the distribution of hydraulic conductivities can be described by inverse power laws specific to the aquifer litho-type. Observed groundwater flow directions reflect this multi-scale structure. The proposed integrated approach applies widely available investigative tools to identify key dominant structures controlling groundwater flow, characterising the aquifer type for each catchment and resolving the spatial distribution of relevant aquifer units and associated hydrodynamic parameters.

An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid

Nucleotide-binding oligomerization domain protein 1 (NOD1) belongs to a family that includes multiple members with NOD and leucine-rich repeats in vertebrates and plants. NOD1 has been suggested to have a role in innate immune responses, but the mechanism involved remains unknown. Here we report that NOD1 mediates the recognition of peptidoglycan derived primarily from Gram-negative bacteria. Biochemical and functional analyses using highly purified and synthetic compounds indicate that the core structure recognized by NOD1 is a dipeptide, gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Murine macrophages deficient in NOD1 did not secrete cytokines in response to synthetic iE-DAP and did not prime the lipopolysaccharide response. Thus, NOD1 mediates selective recognition of bacteria through detection of iE-DAP-containing peptidoglycan.

Photodynamic Antimicrobial Chemotherapy (PACT) in combination with antibiotics for treatment of Burkholderia cepacia complex infection

This study aimed to determine if Photodynamic Antimicrobial Chemotherapy (PACT) was effective in the treatment of Burkholderia cepacia complex infection and whether a synergistic effect was evident if PACT was used in combination with antibiotics. The susceptibility of both planktonic and biofilm cultures of B. cepacia complex strains to methylene blue (MB) and meso-tetra(n-methyl-4-pyridyl)porphine tetra-tosylate (TMP)-mediated PACT was determined alone and in combination with antibiotics used in the treatment of Cystic Fibrosis pulmonary infection caused by these bacteria. When B. cepacia complex strains were grown planktonically, high levels of kill of were achieved with both TMP and MB-mediated PACT with strain and photosensitizer specific differences apparent. When strains were grown in biofilm, antibiotic treatment alone was bactericidal in 17/36 (47%) strain/antibiotic combinations tested. When antibiotic treatment was combined with PACT, bactericidal activity was apparent for 33/36 (92%) strain/antibiotic combinations. No antagonism was detected between PACT and antibiotic treatment with the combination synergistic for 6/36 (17%) and indifferent for 30/36 (83%) strain/antibiotic combinations. PACT could be a viable treatment option, either alone or in combination with antibiotics for treatment of B. cepacia complex pulmonary infection.

Multilevel election timing - A comparative overview

This article investigates the link between regionalization of the structure of government, regional elections and regionalism on the one hand, and the organization of state-wide political parties in Spain and the UK on the other. It particularly looks at two aspects of the relations between the central and regional levels of party organization: integration of the regional branches in central decision making and autonomy of the regional branches. It argues that the party factors are the most crucial elements explaining party change and that party leaders mediate between environmental changes and party organization. The parties' history and beliefs and the strength of the central leadership condition their ability or willingness to facilitate the emergence of meso-level elites. The institutional and electoral factors are facilitating factors that constitute additional motives for or against internal party decentralization.

Devolution and party organizational change: The British and Spanish and state-wide parties compared

This article investigates the link between regionalization of the structure of government, regional elections and regionalism on the one hand, and the organization of state-wide political parties in Spain and the UK on the other. It particularly looks at two aspects of the relations between the central and regional levels of party organization: integration of the regional branches in central decision making and autonomy of the regional branches. It argues that the party factors are the most crucial elements explaining party change and that party leaders mediate between environmental changes and party organization. The parties' history and beliefs and the strength of the central leadership condition their ability or willingness to facilitate the emergence of meso-level elites. The institutional and electoral factors are facilitating factors that constitute additional motives for or against internal party decentralization

Party organisation in a multi-level system: Party organisational change in Spain and the UK

This article investigates the link between regionalization of the structure of government, regional elections and regionalism on the one hand, and the organization of state-wide political parties in Spain and the UK on the other. It particularly looks at two aspects of the relations between the central and regional levels of party organization: integration of the regional branches in central decision making and autonomy of the regional branches. It argues that the party factors are the most crucial elements explaining party change and that party leaders mediate between environmental changes and party organization. The parties' history and beliefs and the strength of the central leadership condition their ability or willingness to facilitate the emergence of meso-level elites. The institutional and electoral factors are facilitating factors that constitute additional motives for or against internal party decentralization.

Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy

The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and IMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS.

The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 mu gml(-1), 6.37-4.59 mu gml(-1) and 11.73-36.57 mu gml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of IMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds. (c) 2012 Elsevier B.V. All rights reserved.

Buckling and Postbuckling Structures: Experimental, Analytical and Numerical Studies

This book provides an in-depth treatment of the study of the stability of engineering structures. Contributions from internationally recognized leaders in the field ensure a wide coverage of engineering disciplines in which structural stability is of importance, in particular the analytical and numerical modelling of structural stability applied to aeronautical, civil, marine and offshore structures. The results from a number of comprehensive experimental test programs are also presented, thus enhancing our understanding of stability phenomena as well as validating the analytical and computational solution schemes presented. A variety of structural materials are investigated with special emphasis on carbon-fibre composites, which are being increasingly utilized in weight-critical structures. Instabilities at the meso- and micro-scales are also discussed. This book will be particularly relevant to professional engineers, graduate students and researchers interested in structural stability.

Textbook (non-) adoption motives, legitimizing strategies and academic field configuration

Textbooks are an integral part of structured syllabus coverage in higher education. The argument advanced in this article is that textbooks are not simply products of inscription and embodied scholarly labour for pedagogical purposes, but embedded institutional artefacts that configure entire academic subject fields. Empirically, this article shows the various ways that motives of the (non-) adoption of textbooks have field institutional configuration effects. The research contribution of our study is threefold. First, we re-theorise the textbook as an artefact that is part of the institutional work and epistemic culture of academia. Second, we empirically show that the vocabularies of motive of textbook (non-) adoption and rhetorical strategies form the basis for social action and configuration across micro, meso and macro field levels. Our final contribution is a conceptualization of the ways that textbook (non-) adoption motives ascribe meaning to the legitimating processes in the configuration of whole subject fields.