Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts: Evolving designer catalysts from polyfunctional cytochrome P450 enzymes

1. Biological catalysts have the advantage of being able to catalyse chemical reactions with an often exquisite degree of regio- and stereospecificity in contrast with traditional methods of organic synthesis. 2. The cytochrome P450 enzymes involved in human drug metabolism are ideal starting materials for the development of designer biocatalysts by virtue of their catalytic versatility and extreme substrate diversity. Applications can be envisaged in fine chemical synthesis, such as in the pharmaceutical industry and bioremediation. 3. A variety of techniques of enzyme engineering are currently being applied to P450 enzymes to explore their catalytic potential. Although most studies to date have been performed with bacterial P450s, reports are now emerging of work with mammalian forms of the enzymes. 4. The present minireview will explore the rationale and general techniques for redesigning P450s, review the results obtained to date with xenobiotic-metabolising forms and discuss strategies to overcome some of the logistic problems limiting the full exploitation of these enzymes as industrial-scale biocatalysts.

Intra- vs intermolecular photoinduced electron transfer reactions of a macrocyclic donor-acceptor dyad

The synthesis, structural characterization, and photophysical behavior of a 14-membered tetraazamacrocycle with pendant 4-dimethylaminobenzyl (DMAB) and 9-anthracenylmethyl groups is reported (L-3, 6-((9-anthracenylmethyl)amino)-trans-6,13-dimethyl-13-((4-dimethylaminobenzyl)amino)-1,4,8,11-tetraaza-cyclotetradecane). In its free base form, this compound displays rapid intramolecular photoinduced electron transfer (PET) quenching of the anthracene emission, with both the secondary amines and the DMAB group capable of acting as electron donors. When complexed with Zn(II), the characteristic fluorescence of the anthracene chromophore is restored as the former of these pathways is deactivated by coordination. Importantly, it is shown that the DMAB group, which remains uncoordinated and PET active, acts only very weakly to quench emission, by comparison to the behavior of a model Zn complex lacking the pendant DMAB group, [ZnL2](2+) (Chart 1). By contrast, Stern-Volmer analysis of intermolecular quenching of [ZnL2](2+) by N,N-dimethylaniline (DMA) has shown that this reaction is diffusion limited. Hence, the pivotal role of the bridge in influencing intramolecular PET is highlighted.

Comparative Analysis of Structural and Morphological Properties of Large-Pore Periodic Mesoporous Organosilicas and Pure Silicas

A systematic study on the structural properties and external morphologies of large-pore mesoporous organosilicas synthesized using triblock copolymer EO20PO70EO20 as a template under low-acid conditions was carried out. By employing the characterization techniques of SAXS, FE-SEM, and physical adsorption of N-2 in combination with alpha(s)-plot method, the structural properties and external morphologies of large-pore mesoporous organosilicas were critically examined and compared with that of their pure-silica counterparts synthesized under similar conditions. It has been observed that unlike mesoporous pure silicas, the structural and morphological properties of mesoporous organosilicas are highly acid-sensitive. High-quality mesoporous organosilicas can only be obtained from synthesis gels with the molar ratios of HCl/H2O between 7.08 x 10(-4) and 6.33 x 10(-3), whereas mesoporous pure silicas with well-ordered structure can be obtained in a wider range of acid concentration. Simply by adjusting the HCl/H2O molar ratios, the micro-, meso-, and macroporosities of the organosilica materials can be finely tuned without obvious effect on their structural order. Such a behavior is closely related to their acid-controlled morphological evolution: from necklacelike fibers to cobweb-supported pearl-like particles and to nanosized particulates.

A complex systems approach to the value of ecological resources

A theory of value sits at the core of every school of economic thought and directs the allocation of resources to competing uses. Ecological resources complicate the modem neoclassical approach to determining value due to their complex nature, considerable non-market values and the difficulty in assigning property rights. Application of the market model through economic valuation only provides analytical solutions based on virtual markets, and neither the demand nor supply-side techniques of valuation can adequately consider the complex set of biophysical and ecological relations that lead to the provision of ecosystem goods and services. This paper sets out a conceptual framework for a complex systems approach to the value of ecological resources. This approach is based on there being both an intrinsic quality of ecological resources and a subjective evaluation by the consumer. Both elements are necessary for economic value. This conceptual framework points the way towards a theory of value that incorporates both elements, so has implications for principles by which ecological resources can be allocated. (c) 2005 Elsevier B.V. All rights reserved.

Observing a coherent superposition of an atom and a molecule

We demonstrate that it is possible, in principle, to perform a Ramsey-type interference experiment to exhibit a coherent superposition of a single atom and a diatomic molecule. This gedanken experiment, based on the techniques of Aharonov and Susskind [Phys. Rev. 155, 1428 (1967)], explicitly violates the commonly accepted superselection rule that forbids coherent superpositions of eigenstates of differing atom number. A Bose-Einstein condensate plays the role of a reference frame that allows for coherent operations analogous to Ramsey pulses. We also investigate an analogous gedanken experiment to exhibit a coherent superposition of a single boson and a fermion, violating the commonly accepted superselection rule forbidding coherent superpositions of states of differing particle statistics. In this case, the reference frame is realized by a multimode state of many fermions. This latter case reproduces all of the relevant features of Ramsey interferometry, including Ramsey fringes over many repetitions of the experiment. However, the apparent inability of this proposed experiment to produce well-defined relative phases between two distinct systems each described by a coherent superposition of a boson and a fermion demonstrates that there are additional, outstanding requirements to fully lift the univalence superselection rule.

Toxinology in Australia's colonial era: A chronology and perspective of human envenomation in 19th century Australia

The medical management of those envenomed by snakes, spiders and poisonous fish in Australia featured extensively in the writings 19th century doctors, expeditioners and anthropologists. Against the background of this introduced medical doctrine there already existed an extensive tradition of Aboriginal medical lore; techniques of heat treatment, suction, incision and the application of plant-derived pharmacological substances featured extensively in the management of envenomed victims. The application of a hair-string or grass-string ligature, suctioning of the bite-site and incision were practised in a variety of combinations. Such evolved independently of and pre-dated such practices, which were promoted extensively by immigrant European doctors in the late 19th century. Pacific scientific toxinology began in the 17th century with Don Diego de Prado y Tovar's 1606 account of ciguatera. By the end of the 19th century more than 30 papers and books had defined the natural history of Australian elapid poisoning. The medical management of snakebite in Australia was the focus of great controversy from 1860 to 1900. Dogmatic claims of the supposed antidote efficacy of intravenous ammonia by Professor G.B. Halford, and that of strychnine by Dr. Augustus Mueller, claimed mainstream medical attention. This era of potential iatrogenic disaster and dogma was brought to a conclusion by the objective experiments of Joseph Lauterer and Thomas Lane Bancroft in 1890 in Brisbane; and by those of C.J. Martin (from 1893) and Frank Tidswell (from 1898), both of Sydney. The modern era of Australian toxinology developed as a direct consequence of Calmette's discovery, in Paris in 1894, of immune serum, which was protective against snakebite. We review the key contributors and discoveries of toxinology in colonial Australia.

Developing context-aware pervasive computing applications: Models and approach

There is growing interest in the use of context-awareness as a technique for developing pervasive computing applications that are flexible, adaptable, and capable of acting autonomously on behalf of users. However, context-awareness introduces a variety of software engineering challenges. In this paper, we address these challenges by proposing a set of conceptual models designed to support the software engineering process, including context modelling techniques, a preference model for representing context-dependent requirements, and two programming models. We also present a software infrastructure and software engineering process that can be used in conjunction with our models. Finally, we discuss a case study that demonstrates the strengths of our models and software engineering approach with respect to a set of software quality metrics.

A composite leading indicator of the inflation cycle for the Euro area

We evaluate the performance of composite leading indicators of turning points of inflation in the Euro area, constructed by combining the techniques of Fourier analysis and Kalman filters with the National Bureau of Economic Research methodology. In addition, the study compares the empirical performance of Euro Simple Sum and Divisia monetary aggregates and provides a tentative answer to the issue of whether or not the UK should join the Euro area. Our findings suggest that, first, the cyclical pattern of the different composite leading indicators very closely reflect that of the inflation cycle for the Euro area; second, the empirical performance of the Euro Divisia is better than its Simple Sum counterpart and third, the UK is better out of the Euro area. © 2005 Taylor & Francis Group Ltd.

Statistical study of talk spurts and silence lengths with relation to various languages and speakers for advanced silence suppression in Next Generation Wireless Communication Devices

As wireless network technologies evolve towards an All-IP framework, Next Generation Wireless Communication Devices demand better use of spectral resources by employing advanced techniques of silence suppression. This paper presents an analysis of VoIP call data and compares the statistical results based on observed patterns of talk spurts and silence lengths to those achieved by a modified on-off voice model for silence suppression in wireless networks. As talk spurts and silence lengths are sensitive to varying word lengths, temporal structure and other prosodic aspects of speech, the impact of the use of various languages, dialects and gender of speakers on these results is also assessed.

Evaluating corporate performance:a critique of economic value added

There has been a revival of interest in economic techniques to measure the value of a firm through the use of economic value added as a technique for measuring such value to shareholders. This technique, based upon the concept of economic value equating to total value, is founded upon the assumptions of classical liberal economic theory. Such techniques have been subject to criticism both from the point of view of the level of adjustment to published accounts needed to make the technique work and from the point of view of the validity of such techniques in actually measuring value in a meaningful context. This paper critiques economic value added techniques as a means of calculating changes in shareholder value, contrasting such techniques with more traditional techniques of measuring value added. It uses the company Severn Trent plc as an actual example in order to evaluate and contrast the techniques in action. The paper demonstrates discrepancies between the calculated results from using economic value added analysis and those reported using conventional accounting measures. It considers the merits of the respective techniques in explaining shareholder and managerial behaviour and the problems with using such techniques in considering the wider stakeholder concept of value. It concludes that this economic value added technique has merits when compared with traditional accounting measures of performance but that it does not provide the universal panacea claimed by its proponents.

Source coded image data in the presence of channel errors

The growth and advances made in computer technology have led to the present interest in picture processing techniques. When considering image data compression the tendency is towards trans-form source coding of the image data. This method of source coding has reached a stage where very high reductions in the number of bits representing the data can be made while still preserving image fidelity. The point has thus been reached where channel errors need to be considered, as these will be inherent in any image comnunication system. The thesis first describes general source coding of images with the emphasis almost totally on transform coding. The transform technique adopted is the Discrete Cosine Transform (DCT) which becomes common to both transform coders. Hereafter the techniques of source coding differ substantially i.e. one tech­nique involves zonal coding, the other involves threshold coding. Having outlined the theory and methods of implementation of the two source coders, their performances are then assessed first in the absence, and then in the presence, of channel errors. These tests provide a foundation on which to base methods of protection against channel errors. Six different protection schemes are then proposed. Results obtained, from each particular, combined, source and channel error protection scheme, which are described in full are then presented. Comparisons are made between each scheme and indicate the best one to use given a particular channel error rate.

Fabrication and applications of fibre Bragg gratings

The consequences of fabricating Bragg gratings in various fibres, with or without hydrogen loading, and with varying laser power levels are explored. Three new techniques for fabricating chirped gratings are presented. Beams with dissimilar wavefront curvatures are interfered to give chirped gratings. With the same aim techniques of writing gratings on tapered fibres and on deformed fibres are also covered. With these techniques, a wide variety of gratings has been fabricated from the 'superbroad' (with bandwidths of up to 180 nm), small to medium bandwidth gratings with linear chirp profiles and quadratic chirped gratings. It is demonstrated that chirped grating can be concatenated to form all-fibre Fabry-Perot and Moiré resonators. These are further concatenated with chirped gratings to produce filters with narrow passbands and very broad stopbands. A number of other applications are also addressed. The use of chirped fibre gratings for dispersion compensation and femtosecond chirped pulse amplification is demonstrated. Chirped gratings are used as dispersive elements in modelocked fibre lasers producing ultrashort pulses. A chirped fibre grating Fabry-Perot transmission filter is used in a continuous wave laser that exhibits eleven simultaneously lasing wavelengths. Finally, the use of grating-coupler devices as variable reflectivity mirrors for laser optimisation and gain clamping is considered.

Spatial arrangement patterns of senile plaques in post-mortem senile dementia of the Alzheimer type brains

We have studied the spatial distribution of plaques in coronal and tangential sections of the parahippocampal gyrus (PHG), the hippocampus, the frontal lobe and the temporal lobe of five SDAT patients. Sections were stained with cresyl violet and examined at two magnifications (x100 and x400). in all cases (and at both magnifications) statistical analysis using the Poisson distribution showed that the plaques were arranged in clumps (x100: V/M = 1.48 - 4.49; x400 V/M = 1.17 - 1.95). this indicates that both large scale and small scale clumping occurs. Application of the statistical techniques of pattern analysis to coronal sections of frontal and temporal cortex and PHG showed. furthermore, that both large (3200-6400 micron) and small scale (100 - 400 micron) clumps were arranged with a high degree of regularity in the tissue. This suggests that the clumps of plaques reflect underlying neural structure.

Odour pollution problems within the district of the Wrekin council

This thesis is concerned with various aspects of Air Pollution due to smell, the impact it has on communities exposed to it, the means by which it may be controlled and the manner in which a local authority may investigate the problems it causes. The approach is a practical one drawing on examples occurring within a Local Authority's experience and for that reason the research is anecdotal and is not a comprehensive treatise on the full range of options available. Odour Pollution is not yet a well organised discipline and might be considered esoteric as it is necessary to incorporate elements of science and the humanities. It has been necessary to range widely across a number of aspects of the subject so that discussion is often restricted but many references have been included to enable a reader to pursue a particular point in greater depth. In a `fuzzy' subject there is often a yawning gap separating theory and practice, thus case studies have been used to illustrate the interplay of various disciplines in resolution of a problem. The essence of any science is observation and measurement. Observation has been made of the spread of odour pollution through a community and also of relevant meterological data so that a mathematical model could be constructed and its predictions checked. It has been used to explore the results of some options for odour control. Measurements of odour perception and human behaviour seldom have the precision and accuracy of the physical sciences. However methods of social research enabled individual perception of odour pollution to be quantified and an insight gained into reaction of a community exposed to it. Odours have four attributes that can be measured and together provide a complete description of its perception. No objective techniques of measurement have yet been developed but in this thesis simple, structured procedures of subjective assessment have been improvised and their use enabled the functioning of the components of an odour control system to be assessed. Such data enabled the action of the system to be communicated using terms that are understood by a non specialist audience.

A composite framework for the strategic alignment of information systems development

Information systems are corporate resources, therefore information systems development must be aligned with corporate strategy. This thesis proposes that effective strategic alignment of information systems requires information systems development, information systems planning and strategic management to be united. Literature in these areas is examined, breaching the academic boundaries which separate these areas, to contribute a synthesised approach to the strategic alignment of information systems development. Previous work in information systems planning has extended information systems development techniques, such as data modelling, into strategic planning activities, neglecting techniques of strategic management. Examination of strategic management in this thesis, identifies parallel trends in strategic management and information systems development; the premises of the learning school of strategic management are similar to those of soft systems approaches to information systems development. It is therefore proposed that strategic management can be supported by a soft systems approach. Strategic management tools and techniques frame individual views of a strategic situation; soft systems approaches can integrate these diverse views to explore the internal and external environments of an organisation. The information derived from strategic analysis justifies the need for an information system and provides a starting point for information systems development. This is demonstrated by a composite framework which enables each information system to be justified according to its direct contribution to corporate strategy. The proposed framework was developed through action research conducted in a number of organisations of varying types. This suggests that the framework can be widely used to support the strategic alignment of information systems development, thereby contributing to organisational success.