Synthesis and characterization of copper(II) complexes of pyridine-2-carboxamidrazones as potent antimalarial agents

Copper(II) complexes of some pyridine-2-carboxamidrazones have been prepared and characterized. The crystal structures of the copper complex cis-[dichloro(N1-2-acetylthiophene-pyridine-2-carboxamidrazone) copper(II)] 8a and one of the free ligands, viz. {(p-chloro-2-thioloxy-benzylidine-pyridine-2-carboxamidrazone)} 6, have been determined. The former shows a highly distorted square planar geometry around copper, with weak intermolecular coordination from the thiophenyl sulfur resulting in a stacking arrangement in the crystal lattice. The in vitro activities of the synthesized compounds against the malarial parasite Plasmodium falciparum are reported for the first time, which clearly shows the advantage of copper complexation and the requirement of four coordinate geometry around copper as some of the key structural features for designing such metal-based antimalarials. © 2003 Elsevier Science B.V. All rights reserved.

Selective recognition of cyclic GMP using a fluorescence-based molecularly imprinted polymer

Guanosine 3′,5′-cyclic monophosphate (cGMP) plays a role as a second messenger in many different biological systems. Given the ubiquitous nature of cGMP, a simple method of detecting cGMP is of interest. To that end a fluorescent polymer with recognition sites for cGMP has been prepared. Its selectivity and sensitivity were investigated and a dose-dependant decrease in fluorescence of the polymer in the presence of cGMP was observed. In contrast, virtually no effect was detected upon application of the structurally similar molecules, guanosine 5′-monophosphate (GMP) and adenosine 3′,5′-cyclic monophosphate (cAMP), thus demonstrating the high selectivity of this polymer. The association constant for the binding of cGMP to the imprinted polymer was determined in order of 3 × 10 5 M -1. A fluorescent, molecularly imprinted polymer that selectively recognises cGMP may have a useful application as a fluorescent chemosensor for cGMP detection in biological samples.

Motherhood on ice? A media framing analysis of older mothers in the UK news

Changing gender roles and increased sexual and economic freedom have created opportunities for women to give birth relatively late in life. However, stigma and misplaced fears about physical capacity are often reported as sources of anxiety among older, and in vitro fertilisation-induced mothers. In this study, we apply a specially adapted method for analysing news media content to a week's selection of material in the British media following the dissemination of research at an international medical conference. Our findings suggest, despite some positive commentaries, that much negative discourse is circulated by the media about older mothers, from implied claims of selfishness (older mothers as 'delaying' conception) to violations of the 'natural order'. These latter claims reflect the long-standing ambivalence by the media generally towards scientific advancement, but they also reveal continuing resistance towards unorthodox lifestyles.

Actionable strategy knowledge:a practice perspective

Increasingly the body of knowledge derived from strategy theory has been criticized because it is not actionable in practice, particularly under the conditions of a knowledge economy. Since strategic management is an applied discipline this is a serious criticism. However, we argue that the theory-practice question is too simple. Accordingly, this paper expands this question by outlining first the theoretical criteria under which strategy theory is not actionable, and then outlines an alternative perspective on strategy knowledge in action, based upon a practice epistemology. The paper is in three sections. The first section explains two contextual conditions which impact upon strategy theory within a knowledge economy, environmental velocity and knowledge intensity. The impact of these contextual conditions upon the application of four different streams of strategy theory is examined. The second section suggests that the theoretical validity of these contextual conditions breaks down when we consider the knowledge artifacts, such as strategy tools and frameworks, which arise from strategy research. The third section proposes a practice epistemology for analyzing strategy knowledge in action that stands in contrast to more traditional arguments about actionable knowledge. From a practice perspective, strategy knowledge is argues to be actionable as part of the everyday activities of strategizing. © 2006 Elsevier Ltd. All rights reserved.

Mathematical modelling and optimisation of a water heat pump

The purpose of the work described here has been to seek methods of narrowing the present gap between currently realised heat pump performance and the theoretical limit. The single most important pre-requisite to this objective is the identification and quantitative assessment of the various non-idealities and degradative phenomena responsible for the present shortfall. The use of availability analysis has been introduced as a diagnostic tool, and applied to a few very simple, highly idealised Rankine cycle optimisation problems. From this work, it has been demonstrated that the scope for improvement through optimisation is small in comparison with the extensive potential for improvement by reducing the compressor's losses. A fully instrumented heat pump was assembled and extensively tested. This furnished performance data, and led to an improved understanding of the systems behaviour. From a very simple analysis of the resulting compressor performance data, confirmation of the compressor's low efficiency was obtained. In addition, in order to obtain experimental data concerning specific details of the heat pump's operation, several novel experiments were performed. The experimental work was concluded with a set of tests which attempted to obtain definitive performance data for a small set of discrete operating conditions. These tests included an investigation of the effect of two compressor modifications. The resulting performance data was analysed by a sophisticated calculation which used that measurements to quantify each dagradative phenomenon occurring in that compressor, and so indicate where the greatest potential for improvement lies. Finally, in the light of everything that was learnt, specific technical suggestions have been made, to reduce the losses associated with both the refrigerant circuit and the compressor.

Preliminary in vitro toxicological evaluation of a series of 2-pyridylcarboxamidrazone candidate anti-tuberculosis compounds III

We have evaluated the cytotoxicity of a series of novel anti-tubercular 2-pyridyl carboxamidrazones through incubation with human mononuclear leucocytes (MNL), with and without a rat microsomal metabolising system. Isoniazid (INH), the closest structurally related agent, was used as a positive control. Incubation of the 3-benzyloxy-benzylidene, dimethylpropyl-benzylidene and 4-phenyl-benzylidene with MNL showed no significant toxicity in comparison with either INH or DMSO vehicle control. However, the 4-N,N-dimethylamino-1-naphthylidene derivative exerted more than sevenfold greater toxicity compared with INH, while the 4-N,N-dimethylamino-1-naphthylidene, 2-benzyloxy-3-methoxy-benzylidene, 2-t-butylthio-benzylidene and 4-i-propyl-benzylidene derivatives showed toxicity which ranged from five to fourfold that of INH. In the presence of either rat microsomes with or without NADPH, the 3-benzyloxy-benzylidene, dimethylpropyl-benzylidene and 4-phenyl-benzylidene derivatives showed no metabolically-mediated cytotoxicity. The latter two derivatives showed a combination of low toxicity and considerable efficacy against Mycobacteria tuberculosis in vitro and show promise for future development. © 2001 Elsevier Science B.V.

Task-based annotation and retrieval for image information management

Continuing advances in digital image capture and storage are resulting in a proliferation of imagery and associated problems of information overload in image domains. In this work we present a framework that supports image management using an interactive approach that captures and reuses task-based contextual information. Our framework models the relationship between images and domain tasks they support by monitoring the interactive manipulation and annotation of task-relevant imagery. During image analysis, interactions are captured and a task context is dynamically constructed so that human expertise, proficiency and knowledge can be leveraged to support other users in carrying out similar domain tasks using case-based reasoning techniques. In this article we present our framework for capturing task context and describe how we have implemented the framework as two image retrieval applications in the geo-spatial and medical domains. We present an evaluation that tests the efficiency of our algorithms for retrieving image context information and the effectiveness of the framework for carrying out goal-directed image tasks. © 2010 Springer Science+Business Media, LLC.

Managing the threat of terrorism in British travel and leisure organizations

Purpose - To study how the threats of terrorism are being handled by a variety of UK companies in the travel and leisure sector in the UK in the post 9/11 era. Design/methodology/approach - A review of the literature of risk management in a world that is perceived to be more risky as a result of the terrorist attacks on the US on 11 September 2001 (9/11) is presented. Describes the application of theories of organizational resilience and institutions to frame an understanding of how managers make sense of terrorism risk and comprehend uncertainty. Reports a qualitative analysis of themes in interviews conducted with 25 managers from 6 unnamed organizations in the aviation industry (3 organizations) and the UK travel and leisure industry (3 organizations), representing a catering supplier, an airport, an airline, a tour company, a convention centre, and an arts and entertainment centre. Findings - The results indicated that the three organizations in the aviation industry prioritize threats from terrorism, whilst the three organizations in the leisure and travel sector do not, suggesting that the managers in the travel and leisure industry apply a probabilistic type of thinking and believe the likelihood of terrorism to be low. Reports that they give precedence to economic concerns and numerous other threats to the industry. Concludes that managers fall prey to the 'ludic fallacy', which conceives all odds as being calculable and hence managers conceive the terrorism risk as low while also expecting institutional factors to pre-empt and control terrorism threats, a reaction which the authors believe to be rather complacent and dangerous. Originality/value - Contributes to the research literature on risk management by revealing the gap in the ability of existing management tools and methodologies to deal with current and uncertain threats facing organizations due to terrorism.

Extreme events, organizations and the politics of decision making

Purpose – Threats of extreme events, such as terrorist attacks or infrastructure breakdown, are potentially highly disruptive events for all types of organizations. This paper seeks to take a political perspective to power in strategic decision making and how this influences planning for extreme events. Design/methodology/approach – A sample of 160 informants drawn from 135 organizations, which are part of the critical national infrastructure in the UK, forms the empirical basis of the paper. Most of these organizations had publicly placed business continuity and preparedness as a strategic priority. The paper adopts a qualitative approach, coding data from focus groups. Findings – In nearly all cases there is a pre-existing dominant coalition which keeps business continuity decisions off the strategic agenda. The only exceptions to this are a handful of organizations which provide continuous production, such as some utilities, where disruption to business as usual can be readily quantified. The data reveal structural and decisional elements of the exercise of power. Structurally, the dominant coalition centralizes control by ensuring that only a few functional interests participate in decision making. Research limitations/implications – Decisional elements of power emphasize the dominance of calculative rationality where decisions are primarily made on information and arguments which can be quantified. Finally, the paper notes the recursive aspect of power relations whereby agency and structure are mutually constitutive over time. Organizational structures of control are maintained, despite the involvement of managers charged with organizational preparedness and resilience, who remain outside the dominant coalition. Originality/value – The paper constitutes a first attempt to show how planning for emergencies fits within the strategy-making process and how politically controlled this process is.

Humanism and instrumentalism in management ethics across seven countries

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Effect of catechol derivatives on cell growth and lipoxygenase activity

Derivatives of salicylic acid have been synthesized as potential lipoxygenase inhibitors. Agents containing a phenolic dihydroxy moiety showed potent (IC 5010 -6-10 -7 M) inhibition of the growth of murine colonic tumour cells in vitro, and were effective inhibitors of 5-, 12- and 15-lipoxygenase in intact cells. The catechols were also potent inhibitors of rabbit reticulocyte 15-lipoxygenase (IC 50 ∼1 μM). © 2003 Elsevier Ltd. All rights reserved.

Mobile case-based decision support for intelligent patient knowledge management

Hospitals everywhere are integrating health data using electronic health record (EHR) systems, and disparate and multimedia patient data can be input by different caregivers at different locations as encapsulated patient profiles. Healthcare institutions are also using the flexibility and speed of wireless computing to improve quality and reduce costs. We are developing a mobile application that allows doctors to efficiently record and access complete and accurate real-time patient information. The system integrates medical imagery with textual patient profiles as well as expert interactions by healthcare personnel using knowledge management and case-based reasoning techniques. The application can assist other caregivers in searching large repositories of previous patient cases. Patients' symptoms can be input to a portable device and the application can quickly retrieve similar profiles which can be used to support effective diagnoses and prognoses by comparing symptoms, treatments, diagnosis, test results and other patient information. © 2007 Sage Publications.

Novel anti-bacterials against MRSA:Synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones

Mucobromic and mucochloric acid were used as building blocks for the construction of a chemical combinatorial library of 3,4,5-trisubstituted 2(5H)-furanones. With these 2 butenolide building blocks, and eight alcohols a sublibrary of 16 dihalogenated 5-alkoxy-2(5H)-furanones was prepared. This sublibrary of 5-alkoxylated furanones was reacted with 16 amines generating a full size focussed combinatorial library of 256 individual compounds. This three dimensional combinatorial library of 3-halogen-4-amino-5-alkoxy-2(5H)-furanones was prepared around the benzimidazolyl furanone lead structure by applying a solution phase combinatorial chemistry concept. Typical representatives of the library were purified and fully characterized and one x-ray structures was recorded, additionally. The 3-bromo-4-benzimizazolyl-5-methoxy-2(5H)furanone, Br-A-l, showed an MIC of 8 μg/ml against the multiresistant Staphylococcus aureus ( MRSA). © 2006 Bentham Science Publishers Ltd.