A synthetic route to fully substituted chiral cyclopentylamine derivatives: precursors of carbanucleosides

Removal of silyl protection from D-glucose derived substrate 6 afforded 7, which upon acetonide deprotection followed by reaction with N-benzylhydroxylamine furnished two isomeric isoxazolidinocyclopentane derivatives via spontaneous cyclization of an in situ generated nitrone. The methyl xanthate derivative of the tertiary hydroxyl group of one isomer was isolated and subjected to radical deoxygenation reaction to form epimeric products, while with the other isomer it underwent spontaneous 1,2-elimination to form a mixture of the two possible endocyclic olefins. Hydrogenolytic cleavage of the isoxazolidine rings of the purified products followed by insertion of 5-amino-4-chloropyrimidine moiety and purine ring construction smoothly afforded structurally unique carbanucleoside analogues. Various spectroscopic methods on the synthesized compounds and X-ray analysis on one important intermediate were used to assign the structures and stereochemistry of the products.

Relative order defines a topology for recurrent networks

This paper uses techniques from control theory in the analysis of trained recurrent neural networks. Differential geometry is used as a framework, which allows the concept of relative order to be applied to neural networks. Any system possessing finite relative order has a left-inverse. Any recurrent network with finite relative order also has an inverse, which is shown to be a recurrent network.

A new approach to reduced-order modelling

An error polynomial is defined, the coefficients of which indicate the difference at any instant between a system and a model of lower order approximating the system. It is shown how Markov parameters and time series proportionals of the model can be matched with those of the system by setting error polynomial coefficients to zero. Also discussed is the way in which the error between system and model can be considered as being a filtered form of an error input function specified by means of model parameter selection.

Electron spin resonance study of puff-resolved free radical formation in mainstream cigarette smoke

Puff-by-puff resolved gas phase free radicals were measured in mainstream smoke from Kentucky 2R4F reference cigarettes using ESR spectroscopy. Three spin-trapping reagents were evaluated: PBN, DMPO and DEPMPO. Two procedures were used to collect gas phase smoke on a puff-resolved basis: i) the accumulative mode, in which all the gas phase smoke up to a particular puff was bubbled into the trap (i.e., the 5th puff corresponded to the total smoke from the 1st to 5th puffs). In this case, after a specified puff, an aliquot of the spin trap was taken and analysed; or, ii) the individual mode, in which the spin trap was analysed and then replaced after each puff. Spin concentrations were determined by double-integration of the first derivative of the ESR signal. This was compared with the integrals of known standards using the TEMPO free radical. The radicals trapped with PBN were mainly carbon-centred, whilst the oxygen-centred radicals were identified with DMPO and DEPMPO. With each spin trap, the puff-resolved radical concentrations showed a characteristic pattern as a function of the puff number. Based on the spin concentrations, the DMPO and DEPMPO spin traps showed better trapping efficiencies than PBN. The implication for gas phase free radical analysis is that a range of different spin traps should be used to probe complex free radical reactions in cigarette smoke.

A stress-controlled mechanism for the intensity of very large magnitude explosive eruptions

Large magnitude explosive eruptions are the result of the rapid and large-scale transport of silicic magma stored in the Earth's crust, but the mechanics of erupting teratonnes of silicic magma remain poorly understood. Here, we demonstrate that the combined effect of local crustal extension and magma chamber overpressure can sustain linear dyke-fed explosive eruptions with mass fluxes in excess of 10^10 kg/s from shallow-seated (4–6 km depth) chambers during moderate extensional stresses. Early eruption column collapse is facilitated with eruption duration of the order of few days with an intensity of at least one order of magnitude greater than the largest eruptions in the 20th century. The conditions explored in this study are one way in which high mass eruption rates can be achieved to feed large explosive eruptions. Our results corroborate geological and volcanological evidences from volcano-tectonic complexes such as the Sierra Madre Occidental (Mexico) and the Taupo Volcanic Zone (New Zealand).

Development of a light scatter sensor technology for on-line monitoring of milk coagulation and whey separation

The objective of this study was to investigate a novel light backscatter sensor, with a large field of view relative to curd size, for continuous on-line monitoring of coagulation and syneresis to improve curd moisture content control. A three-level, central composite design was employed to study the effects of temperature, cutting time, and CaCl2 addition on cheese making parameters. The sensor signal was recorded and analyzed. The light backscatter ratio followed a sigmoid increase during coagulation and decreased asymptotically after gel cutting. Curd yield and curd moisture content were predicted from the time to the maximum slope of the first derivative of the light backscatter ratio during coagulation and the decrease in the sensor response during syneresis. Whey fat was affected by coagulation kinetics and cutting time, suggesting curd rheological properties at cutting are dominant factors determining fat losses. The proposed technology shows potential for on-line monitoring of coagulation and syneresis. 2007 Elsevier Ltd. All rights reserved..

Side-chain liquid crystalline elastomers: the relationship between the orientational ordering of the polymer backbone and the length of the coupling chain

The influence of cross-linking on the phase behaviour of a series of side-chain liquid crystalline elastomers has been studied. For samples cross-linked in the temperature range corresponding to the nematic phase, the phase transition was shifted compared to that observed when an identical sample was cross-linked in the isotropic phase. This shift represented a stabilisation of the nematic phase in the former case, in line with theoretical expectations. By utilising a novel, slow cross-linking method, which allows the polymer backbone to take up an equilibrium conformation prior to network formation, it proved possible to monitor the shifts in phase transition temperature as a function of the length of the methylene chain coupling the mesogenic units to the polymer backbone. The results obtained are related to the backbone anisotropy and indicate that the level of orientational order of the polymer in the nematic phase backbone increases with a reduction in the length of the coupling chain.

Expectation versus provision in the management and use of urban open space

This paper discusses the implications of the shifting cultural significance of public open space in urban areas. In particular, it focuses on the increasing dysfunction between people's expectations of that space and its actual provision and management. In doing so, the paper applies Lefebvre's ideas of spatiality to the evident paradigm shift from 'public' to 'private' culture, with its associated commodification of previously public space. While developing the construct of paradigm shift, the paper recognises that the former political notions inherent in the provision of public space remain in evidence. So whereas public parks were formerly seen as spaces of confrontation between the 'rationality' of public order as the 'irrationality' of individual leisure pursuits, they are now increasingly seen, particularly 'out of hours', as the domain of the dispossessed, to be defined and policed as 'dangerous'. Where once people were welcomed into public open spaces as a means of 'educating' them in good, acceptable, leisure practices, therefore, they are now increasingly excluded, but for the same ostensible reasons. Building on survey work undertaken in Reading, Berkshire, the paper illustrates how communities can become separated from 'their' space, leaving them with the overriding impression that they have been 'short-changed' in terms of both the provision and the management of urban open space. Rather than the intimacy of local space for local people, therefore, the paper argues that parks have become externalised places, increasingly responding to commercial definitions of culture and what is 'public'. Central urban open spaces are therefore increasingly becoming sites of stratification, signification of a consumer-constructed citizenship and valorisation of public life as a legitimate element of the market surface of town and city centres.

Incorporation of a S-glycosidic linkage into a glyconucleoside changes the conformational preference of both furanose sugars

A glyconucleoside containing a thioglycoside linkage, namely 1-(3-S-beta-D-ribofuranosyl-2,3-dideoxy-3-thio-beta-D-ribofuranosyl)-thy mine, has been prepared through condensation of a suitably protected derivative of 3'-thiothymidine with an activated ribose sugar. NMR has been used to study the conformation of the S-disaccharide and the unmodified O-disaccharide. A full pseudorotational analysis showed that for the S-disaccharide, the ribose and deoxy ribose sugars have a preference for the south and north pucker, respectively; which is the reverse of what is seen for the O-disaccharide. (c) 2006 Elsevier Ltd. All rights reserved.

Chromium nanostructures formed by dewetting of heteroepitaxial films on W(100)

In this paper, we report the surprising formation of square-based facetted islands with linear dimension of the order of 500 nm upon dewetting of a Cr multilayer onW(100).We show that these square islands are composed of inclined facets surrounding a depressed center such that the facet slopes inward with the outer edges of the islands thicker than the centers. The islands’ shapes do not represent traditional equilibrium crystal shapes as expected for a Wulf construction. In situ UV and x-ray photoelectron emission microscopy allied to spatially resolved spectroscopy throws considerable light on the nature of the dewetting and shows that the metal surface between the islands remains covered by a thin pseudomorphic wetting layer of ∼1 ML. Low-energy electron diffraction and scanning tunneling and atomic force microscopies allow quantification of facet slopes, and we identify a predominance of tilted Cr(100) facets ±5◦ off of the substrate normal bound by (210) planes at ∼26◦. The epitaxial Cr islands adopt the bulk Cr lattice constant but are tilted with respect to the surface normal.We suggest that the Cr crystallite tilting creates a vicinal-like interface structure that determines the island morphology

On the strong uniqueness of some finite dimensional Dirichlet operators

We prove essential self-adjointness of a class of Dirichlet operators in ℝn using the hyperbolic equation approach. This method allows one to prove essential self-adjointness under minimal conditions on the logarithmic derivative of the density and a condition of Muckenhoupt type on the density itself.

A study into the accuracy of using meteorological wind data to estimate turbine generation output

Meteorological (met) station data is used as the basis for a number of influential studies into the impacts of the variability of renewable resources. Real turbine output data is not often easy to acquire, whereas meteorological wind data, supplied at a standardised height of 10 m, is widely available. This data can be extrapolated to a standard turbine height using the wind profile power law and used to simulate the hypothetical power output of a turbine. Utilising a number of met sites in such a manner can develop a model of future wind generation output. However, the accuracy of this extrapolation is strongly dependent on the choice of the wind shear exponent alpha. This paper investigates the accuracy of the simulated generation output compared to reality using a wind farm in North Rhins, Scotland and a nearby met station in West Freugh. The results show that while a single annual average value for alpha may be selected to accurately represent the long term energy generation from a simulated wind farm, there are significant differences between simulation and reality on an hourly power generation basis, with implications for understanding the impact of variability of renewables on short timescales, particularly system balancing and the way that conventional generation may be asked to respond to a high level of variable renewable generation on the grid in the future.

The role of fimbriae and flagella in the adherence of avian strains of Escherichia coli O78:K80 to tissue culture cells and tracheal and gut explants

To investigate the role of fimbriae and flagella in the pathogenesis of avian colibacillosis, isogenic insertionally inactivated mutant strains of Escherichia coil O78:K80 strain EC34195 defective in the elaboration of type-1 and curli fimbriae and flagella were constructed by allelic exchange, Single and multiple non-fimbriate and non-flagellate mutant strains were compared to the wild-type in vitro in adherence assays with a HEp-2 cell line, a mucus-secreting cell line HT2916E, a non-mucus-secreting cell line HT2919A, tracheal explant and proximal gut explant, Mutant strains defective in the elaboration of type-1 fimbriae were significantly less adherent - in the order of 90% reduction - than the wild-type strain in all assays. Mutant strains defective in the elaboration of flagella were generally as adherent as the wild-type strain except when assayed with the mucus-secreting cell line HT2916E, for which a significant reduction of adherence - of the order of 90% - compared with the wild-type strain was observed. Mutant strains defective for the elaboration of curb fimbriae adhered as well as the wild-type strain in all assays, except when assayed in tests with gut explant tissue for which a significant reduction of adherence - of the order of 80% - compared with the wild-type strain was observed, Adherence to explants was to epithelial, not serous, surfaces and was 10-fold greater to tracheal than to gut explants, Together, these data support the hypothesis that type-1 fimbriae are significant factors in adherence, aided by flagella for penetration of mucus and curli fimbriae for adherence to the gut.

The O-antigen of Salmonella enterica serotype Enteritidis PT4: a significant factor in gastrointestinal colonisation of young but not newly hatched chicks

The lipopolysaccharide of Salmonella and other Gram negative pathogenic species has been implicated as a major virulence determinant and in this study we report the role of LPS of S. Enteritidis in the colonisation and persistent gastrointestinal infection of young poultry. The gene encoding the unique O-antigen ligase, waaL, was mutated by insertional inactivation in a well characterised S. Enteritidis strain, S1400/94. The waaL mutant, designated PCP, produced rough colonies on agar medium, did not agglutinate O9 antiserum, did not produce an LPS ladder on silver stained gels and was serum sensitive. PCP and a nalidixic acid marked derivative of S1400/94 (S1400/94 Nal(r)) were used to orally challenge young chicks, separately and together in competitive index experiments. At post-mortem examination of 1-day-old chicks challenged S1400/94 Nal(r) and PCP separately there were no significant differences in the numbers of S1400/94 Nal(r) and PCP bacteria in tissues sampled on days 1, 2. and 5. By day 42 after challenge S1400/94 Nal(r) bacteria were recovered in significantly higher numbers than PCP from the caecal contents (P < 0.001). In competitive index studies in the 1-day-old chick PCP colonised, invaded and persisted in lower numbers than S1400/94 Nal(r). In 4-week-old chicks challenged separately, PCP bacteria were recovered from all tissues examined in significantly lower numbers than S1400/94 Nal(r). In competitive index experiments in 4-week-old chicks, PCP was not detected at any site and at any time point. Therefore, the O-antigen of S. Enteritidis plays art important role in poultry infections although this role is less important in the newly hatched chick. Crown Copyright (C) 2004 Published by Elsevier B.V. All rights reserved.

Fluoroquinolone treatment of experimental Salmonella enterica serovar Typhimurium DT104 infections in chickens selects for both gyrA mutations and changes in efflux pump gene expression

Objectives: To determine the efficacy of enrofloxacin (Baytril) in chickens in eradicating three different resistance phenotypes of Salmonella enterica and to examine the resistance mechanisms of resulting mutants. Methods: In two separate replicate experiments (I and 11), three strains of Salmonella enterica serovar Typhimurium DT104 [strain A, fully antibiotic-sensitive strain; strain B, isogenic multiple antibiotic-resistant (MAR) derivative of A; strain C, veterinary penta-resistant phenotype strain containing GyrA Phe-83], were inoculated into day-old chicks at similar to 10(3) Cfu/bird. At day 10, groups of chicks (n =10) were given either enrofloxacin at 50 ppm in their drinking water for 5 days or water alone (control). Caecal contents were monitored for presence of Salmonella and colonies were replica plated to media containing antibiotics or overlaid with cyclohexane to determine the proportion of isolates with reduced susceptibility. The MICs of antibiotics and cyclohexane tolerance were determined for selected isolates from the chicks. Mutations in topoisomerase genes were examined by DHPLC and expression of marA, soxS, acrB, acrD and acrF by RT-PCR. Results: In experiment 1, but not 11, enrofloxacin significantly reduced the numbers of strain A compared with the untreated control group. In experiment 11, but not 1, enrofloxacin significantly reduced the numbers of strain B. Shedding of strain C was unaffected by enrofloxacin treatment. Birds infected with strains A and B gave rise to isolates with decreased fluoroquinolone susceptibility. Isolates derived from strain A or B requiring > 128 mg/L nalidixic acid for inhibition contained GyrA Asn-82 or Phe-83. Isolates inhibited by 16 mg/L nalidixic acid were also less susceptible to antibiotics of other chemical classes and became cyclohexane-tolerant (e.g. MAR). Conclusions: These studies demonstrate that recommended enrofloxacin treatment of chicks rapidly selects for strains with reduced fluoroquinolone susceptibility from fully sensitive and MAR strains. It can also select for MAR isolates.