Functional model for catecholase-like activity: A mechanistic approach with manganese(III) complexes of salen type Schiff base ligands

Three new Mn(III) complexes [MnL1(OOCH)(OH2)] (1), [MnL2(OH2)(2)][Mn2L22(NO2)(3)] (2) and [Mn2L21(NO2)(2)] (3) (where H2L1 = H(2)Me(2)Salen = 2,7-bis(2-hydroxyphenyl)-2,6-diazaocta-2,6-diene and H2L2 = H(2)Salpn = 1,7-bis(2-hydroxyphenyl)-2,6-diazahepta-1,6-diene) have been synthesized. X-ray crystal structure analysis reveals that 1 is a mononuclear species whereas 2 contains a mononuclear cationic and a dinuclear nitrite bridged (mu-1 kappa O:2 kappa O') anionic unit. Complex 3 is a phenoxido bridged dimer containing terminally coordinated nitrite. Complexes 1-3 show excellent catecholase-like activity with 3,5-di-tert-butylcatechol (3,5-DTBC) as the substrate. Kinetic measurements suggest that the rate of catechol oxidation follows saturation kinetics with respect to the substrate and first order kinetics with respect to the catalyst. Formation of bis(mu-oxo)dimanganese(III,III) as an intermediate during the course of reaction is identified from ESI-MS spectra. The characteristic six line EPR spectra of complex 2 in the presence of 3,5-DTBC supports the formation of manganese(II)-semiquinonate as an intermediate species during the catalytic oxidation of 3,5-DTBC.

A geomatics-based approach for the derivation of the spatial distribution of sediment transport processes in periglacial mountain environments

Within this paper modern techniques such as satellite image analysis and tools provided by geographic information systems (GIS.) are exploited in order to extend and improve existing techniques for mapping the spatial distribution of sediment transport processes. The processes of interest comprise mass movements such as solifluction, slope wash, dirty avalanches and rock- and boulder falls. They differ considerably in nature and therefore different approaches for the derivation of their spatial extent are required. A major challenge is addressing the differences between the comparably coarse resolution of the available satellite data (Landsat TM/ETM+, 30 in x 30 m) and the actual scale of sediment transport in this environment. A three-stepped approach has been developed which is based on the concept of Geomorphic Process Units (GPUs): parameterization, process area delineation and combination. Parameters include land cover from satellite data and digital elevation model derivatives. Process areas are identified using a hierarchical classification scheme utilizing thresholds and definition of topology. The approach has been developed for the Karkevagge in Sweden and could be successfully transferred to the Rabotsbekken catchment at Okstindan, Norway using similar input data. Copyright (C) 2008 John Wiley & Sons, Ltd.

Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.

Functional disconnection of a prefrontal cortical-dorsal striatal system disrupts choice reaction time performance: implications for attentional function

This series of experiments investigated the role of a prefrontal cortical-dorsal striatal circuit in attention, using a continuous performance task of sustained and spatially divided visual attention. A unilateral excitotoxic lesion of the medial prefrontal cortex and a contralateral lesion of the medial caudate-putamen were used to "disconnect" the circuit. Control groups of rats with unilateral lesions of either structure were tested in the same task. Behavioral controls included testing the effects of the disconnection lesion on Pavlovian discriminated approach behavior. The disconnection lesion produced a significant reduction in the accuracy of performance in the attentional task but did not impair Pavlovian approach behavior or affect locomotor or motivational variables, providing evidence for the involvement of this medial prefrontal corticostriatal system in aspects of visual attentional function.

PRISM and ENES: a European approach to Earth system modelling

Europe's widely distributed climate modelling expertise, now organized in the European Network for Earth System Modelling (ENES), is both a strength and a challenge. Recognizing this, the European Union's Program for Integrated Earth System Modelling (PRISM) infrastructure project aims at designing a flexible and friendly user environment to assemble, run and post-process Earth System models. PRISM was started in December 2001 with a duration of three years. This paper presents the major stages of PRISM, including: (1) the definition and promotion of scientific and technical standards to increase component modularity; (2) the development of an end-to-end software environment (graphical user interface, coupling and I/O system, diagnostics, visualization) to launch, monitor and analyse complex Earth system models built around state-of-art community component models (atmosphere, ocean, atmospheric chemistry, ocean bio-chemistry, sea-ice, land-surface); and (3) testing and quality standards to ensure high-performance computing performance on a variety of platforms. PRISM is emerging as a core strategic software infrastructure for building the European research area in Earth system sciences. Copyright (c) 2005 John Wiley & Sons, Ltd.

Towards an assessment of multiple ecosystem processes and services via functional traits

Managing ecosystems to ensure the provision of multiple ecosystem services is a key challenge for applied ecology. Functional traits are receiving increasing attention as the main ecological attributes by which different organisms and biological communities influence ecosystem services through their effects on underlying ecosystem processes. Here we synthesize concepts and empirical evidence on linkages between functional traits and ecosystem services across different trophic levels. Most of the 247 studies reviewed considered plants and soil invertebrates, but quantitative trait–service associations have been documented for a range of organisms and ecosystems, illustrating the wide applicability of the trait approach. Within each trophic level, specific processes are affected by a combination of traits while particular key traits are simultaneously involved in the control of multiple processes. These multiple associations between traits and ecosystem processes can help to identify predictable trait–service clusters that depend on several trophic levels, such as clusters of traits of plants and soil organisms that underlie nutrient cycling, herbivory, and fodder and fibre production. We propose that the assessment of trait–service clusters will represent a crucial step in ecosystem service monitoring and in balancing the delivery of multiple, and sometimes conflicting, services in ecosystem management.

A cross-taxonomic index for quantifying the health of farmland biodiversity

P>1. The development of sustainable, multi-functional agricultural systems involves reconciling the needs of agricultural production with the objectives for environmental protection, including biodiversity conservation. However, the definition of sustainability remains ambiguous and it has proven difficult to identify suitable indicators for monitoring progress towards, and the successful achievement of, sustainability. 2. In this study, we show that a trait-based approach can be used to assess the detrimental impacts of agricultural change to a broad range of taxonomic groupings and derive a standardised index of farmland biodiversity health, built around an objective of achieving stable or increasing populations in all species associated with agricultural landscapes. 3. To demonstrate its application, we assess the health of UK farmland biodiversity relative to this goal. Our results suggest that the populations of two-thirds of 333 plant and animal species assessed are unsustainable under current UK agricultural practices. 4. We then explore the potential benefits of an agri-environment scheme, Entry Level Stewardship (ELS), to farmland biodiversity in the UK under differing levels of risk mitigation delivery. We show that ELS has the potential to make a significant contribution to progress towards sustainability targets but that this potential is severely restricted by current patterns of scheme deployment. 5.Synthesis and applications: We have developed a cross-taxonomic sustainability index which can be used to assess both the current health of farmland biodiversity and the impacts of future agricultural changes relative to quantitative biodiversity targets. Although biodiversity conservation is just one of a number of factors that must be considered when defining sustainability, we believe our cross-taxonomic index has the potential to be a valuable tool for guiding the development of sustainable agricultural systems.

Modeling of relationships between weather and Septoria tritici epidemics on winter wheat: A critical approach

Two models for predicting Septoria tritici on winter wheat (cv. Ri-band) were developed using a program based on an iterative search of correlations between disease severity and weather. Data from four consecutive cropping seasons (1993/94 until 1996/97) at nine sites throughout England were used. A qualitative model predicted the presence or absence of Septoria tritici (at a 5% severity threshold within the top three leaf layers) using winter temperature (January/February) and wind speed to about the first node detectable growth stage. For sites above the disease threshold, a quantitative model predicted severity of Septoria tritici using rainfall during stern elongation. A test statistic was derived to test the validity of the iterative search used to obtain both models. This statistic was used in combination with bootstrap analyses in which the search program was rerun using weather data from previous years, therefore uncorrelated with the disease data, to investigate how likely correlations such as the ones found in our models would have been in the absence of genuine relationships.

Searching efficiency and the functional response of a pause-travel forager

1. The feeding rates of many predators and parasitoids exhibit type II functional responses, with a decelerating rate of increase to reach an asymptotic value as the density of their prey or hosts increases. Holling's disc equation describes such relationships and predicts that the asymptotic feeding rate at high prey densities is set by handling time, while the rate at which feeding rate increases with increased prey density is determined by searching efficiency. Searching efficiency and handling time are also parameters in other models which describe the functional response. Models which incorporate functional responses in order to make predictions of the effects of food shortage thus rely upon a clear understanding and accurate quantification of searching efficiency and handling time. 2. Blackbird Turdus merula exhibit a type II functional response and use pause-travel foraging, a foraging technique in which animals search for prey while stationary and then move to capture prey. Pause-travel foraging allows accurate direct measurement of feeding rate and both searching efficiency and handling time. We use Blackbirds as a model species to: (i) compare observed measures of both searching efficiency and handling time with those estimated by statistically fitting the disc equation to the observed functional response; and (ii) investigate alternative measures of searching efficiency derived by the established method where search area is assumed to be circular and a new method that we propose where it is not. 3. We find that the disc equation can adequately explain the functional response of blackbirds feeding on artificial prey. However, this depends critically upon how searching efficiency is measured. Two variations on the previous method of measuring search area (a component of searching efficiency) overestimated searching efficiency, and hence predicted feeding rates higher than those observed. Two variations of our alternative approach produced lower estimates of searching efficiency, closer to that estimated by fitting the disc equation, and hence more accurately predicted feeding rate. Our study shows the limitations of the previous method of measuring searching efficiency, and describes a new method for measuring searching efficiency more accurately.

A hierarchical Bayesian model for predicting the functional consequences of amino-acid polymorphisms

Genetic polymorphisms in deoxyribonucleic acid coding regions may have a phenotypic effect on the carrier, e.g. by influencing susceptibility to disease. Detection of deleterious mutations via association studies is hampered by the large number of candidate sites; therefore methods are needed to narrow down the search to the most promising sites. For this, a possible approach is to use structural and sequence-based information of the encoded protein to predict whether a mutation at a particular site is likely to disrupt the functionality of the protein itself. We propose a hierarchical Bayesian multivariate adaptive regression spline (BMARS) model for supervised learning in this context and assess its predictive performance by using data from mutagenesis experiments on lac repressor and lysozyme proteins. In these experiments, about 12 amino-acid substitutions were performed at each native amino-acid position and the effect on protein functionality was assessed. The training data thus consist of repeated observations at each position, which the hierarchical framework is needed to account for. The model is trained on the lac repressor data and tested on the lysozyme mutations and vice versa. In particular, we show that the hierarchical BMARS model, by allowing for the clustered nature of the data, yields lower out-of-sample misclassification rates compared with both a BMARS and a frequen-tist MARS model, a support vector machine classifier and an optimally pruned classification tree.

A carbene insertion approach to functionalised poly(ethylene oxide)-based gels

Carbenes photogenerated from the novel bisdiazirine, 1, 3-bis(3-(trifluoromethyl)diazirin-3-yl) benzene 1, have been applied successfully to cross-linking of mono-methyl poly(ethylene oxide) (MePEO5000) in the presence of dichloromethane, leading to the simultaneous incorporation of alkylhalide functionalities. The PEO-based gels swell in a wide range of solvents with polarity index values varying from 3.1 to 9.0. Reaction of the alkylhalide functionalities present in the gels with 4-phenylazophenol provided loading capacities of up to 0.20 mmol g(-1) and demonstrated the potential of these materials for gel-phase synthesis applications. (C) 2008 Elsevier Ltd. All rights reserved.

Contextualist research: Iterating between methods while following an empirically grounded approach

An alternative approach to research is described that has been developed through a succession of significant construction management research projects. The approach follows the principles of iterative grounded theory, whereby researchers iterate between alternative theoretical frameworks and emergent empirical data. Of particular importance is an orientation toward mixing methods, thereby overcoming the existing tendency to dichotomize quantitative and qualitative approaches. The approach is positioned against the existing contested literature on grounded theory, and the possibility of engaging with empirical data in a “theory free” manner is discounted. Emphasis instead is given to the way in which researchers must be theoretically sensitive as a result of being steeped in relevant literatures. Knowledge of existing literatures therefore shapes the initial research design; but emergent empirical findings cause fresh theoretical perspectives to be mobilized. The advocated approach is further aligned with notions of knowledge coproduction and the underlying principles of contextualist research. It is this unique combination of ideas which characterizes the paper's contribution to the research methodology literature within the field of construction management. Examples are provided and consideration is given to the extent to which the emergent findings are generalizable beyond the specific context from which they are derived.

Innovative approach to building systems integration problems: Using systems theory, technological forecasting and scenario planning

Building services are worth about 2% GDP and are essential for the effective and efficient operations of the building. It is increasingly recognised that the value of a building is related to the way it supports the client organisation’s ongoing business operations. Building services are central to the functional performance of buildings and provide the necessary conditions for health, well-being, safety and security of the occupants. They frequently comprise several technologically distinct sub-systems and their design and construction requires the involvement of numerous disciplines and trades. Designers and contractors working on the same project are frequently employed by different companies. Materials and equipment is supplied by a diverse range of manufacturers. Facilities managers are responsible for operation of the building service in use. The coordination between these participants is crucially important to achieve optimum performance, but too often is neglected. This leaves room for serious faults. The need for effective integration is important. Modern technology offers increasing opportunities for integrated personal-control systems for lighting, ventilation and security as well as interoperability between systems. Opportunities for a new mode of systems integration are provided by the emergence of PFI/PPP procurements frameworks. This paper attempts to establish how systems integration can be achieved in the process of designing, constructing and operating building services. The essence of the paper therefore is to envisage the emergent organisational responses to the realisation of building services as an interactive systems network.

Probing a biomimetic approach to Mycaperoxide B: hydroperoxidation studies

Hydroperoxidation studies on a series of alkene substrates demonstrate the introduction of the hydroperoxide functional group into the required position for a biosynthetically inspired synthesis of mycaperoxide B.

Induced-fit binding of π-electron donor substrates to macrocyclic aromatic ether-imide-sulfones: a versatile approach to molecular assembly

Novel macrocyclic receptors which bind electron-donor aromatic substrates via π-stacking donor- acceptor interactions are obtained by cyclo-imidization of an amine-functionalized arylether-sulfone with pyromellitic- and 1,4,5,8-naphthalene-tetracarboxylic dianhydrides. These macrocycles complex with a wide variety of π-donor substrates including tetrathiafulvalene, naphthalene, anthracene, pyrene, perylene, and functional derivatives of these polycyclic hydrocarbons. The resulting supramolecular assemblies range from simple 1:1 complexes, to [2]- and [3]-pseudorotaxanes, and even (as a result of crystallographic disorder) an apparent polyrotaxane. Direct, five-component self-assembly of a metal-centred [3]pseudorotaxane is also observed, on complexation of a macrocyclic ether-imide with 8-hydroxyquinoline in the presence of palladium(II) ions. Binding studies in solution were carried out by 1H NMR and UV-visible spectroscopy, and the stoichiometries of binding were confirmed by Job plots based on charge-transfer absorption bands. The highest association constants are found for strong π-donor guests with large surface-areas, notably perylene and 1-hydroxypyrene, for which Ka values of 1.4 x 103 and 2.3 x 103 M-1 respectively are found. Single crystal X-ray analyses of the receptors and their derived complexes reveal large, induced-fit distortions of the macrocyclic frameworks as a result of complexation. These structures provide compelling evidence for the existence of strong, attractive forces between the electronically-complementary aromatic π-systems of host and guest.