Molecular modelling assisted design and synthesis of cyclothialidine derivatives as DNA gyrase inhibitors

Since cyclothialidine was discovered as the most active DNA gyrase inhibitor in 1994, enormous efforts have been devoted to make it into a commercial medicine by a number of pharmaceutical companies and research groups worldwide. However, no serious breakthrough has been made up to now. An essential problem involved with cyclothialidine is that though it demonstrated the potent inhibition of DNA gyrase, it showed little activity against bacteria. This probably is attributable to its inability to penetrate bacterial cell walls and membranes. We applied the TSAR programme to generate a QSAR equation to the gram-negative organisms. In that equation, LogP is profoundly indicated as the key factor influencing the cyclothialidine activity against bacteria. However, the synthesized new analogues have failed to prove that. In the structure based drug design stage, we designed a group of open chain cyclothialidine derivatives by applying the SPROUT programme and completed the syntheses. Improved activity is found in a few analogues and a 3D pharmacophore of the DNA gyrase B is proposed to lead to synthesis of the new derivatives for development of potent antibiotics.

Field experiments on competition between three foliose lichens using the de Wit experimental design

Competition between three foliose, saxicolous lichens common on slate rock in South Gwynedd, Wales, U.K. was studied experimentally using the de Wit design. Fragments of the three species were cut from the edges of large thalli, glued to 5 x 5 cm plots marked out on pieces of slate which were then placed on boards in the field. For each combination of pairs of species, the two species were grown either in monoculture at a density of 24 fragments per plot or together in three mixtures in differing proportions, i.e. species A:B with 16:8, 12:12 and 8:16 fragments per plot; the density remaining constant throughout. Area of the species in the plots after 3 years was used as an estimate of growth. Physcia orbicularis and Parmelia glabratula ssp. fuliginosa grew similarly in monoculture. In mixtures of the two, growth of each species was linearly related to its proportion in a mixture, suggesting little competition had occurred during three years. By contrast, the growth of Parmelia conspersa in monoculture was significantly greater than that of P. orbicularis or P. glabratula. In addition, the growth of both species was substantially reduced in mixtures with P. conspersa; P. glabratula being eliminated in the mixture in which it was the minority species. These results suggest that P. conspersa should predominate in communities with either of the other two species and, in the absence of P. conspersa, communities dominated by P.orbicularis and P. glabratula should be more stable.

Competition between three lichen species using a factorial experimental design

Competition between three foliose lichens common on slate rock in south Gwynedd, Wales was studied in the field using a factorial experimental design. The lichens were grown as fragments glued to pieces of slate in two- and three-species mixtures. In the two-species mixtures, Parmelia conspersa (Ehrh. Ex Ach.) Ach. outcompeted Parmelia glabratula ssp. fuliginosa (Fr. ex Duby) Laund. strongly and Physcia orbicularis (Neck.) Poetsch less strongly, while P. orbicularis outcompeted P. glabratula weakly. Significant two-factor interactions indicated that the results from the three-species mixture could not be predicted from the two-species mixtures. Parmelia glabratula and P. orbicularis grew better in the presence of two competitors than one. This result suggests that the three species may co-occur on well-lit rock surfaces at the site.

Approximately optimal experimental design for heteroscedastic Gaussian process models

This paper presents a greedy Bayesian experimental design criterion for heteroscedastic Gaussian process models. The criterion is based on the Fisher information and is optimal in the sense of minimizing parameter uncertainty for likelihood based estimators. We demonstrate the validity of the criterion under different noise regimes and present experimental results from a rabies simulator to demonstrate the effectiveness of the resulting approximately optimal designs.

A structural method for the design of fault tolerant distributed control systems

Distributed digital control systems provide alternatives to conventional, centralised digital control systems. Typically, a modern distributed control system will comprise a multi-processor or network of processors, a communications network, an associated set of sensors and actuators, and the systems and applications software. This thesis addresses the problem of how to design robust decentralised control systems, such as those used to control event-driven, real-time processes in time-critical environments. Emphasis is placed on studying the dynamical behaviour of a system and identifying ways of partitioning the system so that it may be controlled in a distributed manner. A structural partitioning technique is adopted which makes use of natural physical sub-processes in the system, which are then mapped into the software processes to control the system. However, communications are required between the processes because of the disjoint nature of the distributed (i.e. partitioned) state of the physical system. The structural partitioning technique, and recent developments in the theory of potential controllability and observability of a system, are the basis for the design of controllers. In particular, the method is used to derive a decentralised estimate of the state vector for a continuous-time system. The work is also extended to derive a distributed estimate for a discrete-time system. Emphasis is also given to the role of communications in the distributed control of processes and to the partitioning technique necessary to design distributed and decentralised systems with resilient structures. A method is presented for the systematic identification of necessary communications for distributed control. It is also shwon that the structural partitions can be used directly in the design of software fault tolerant concurrent controllers. In particular, the structural partition can be used to identify the boundary of the conversation which can be used to protect a specific part of the system. In addition, for certain classes of system, the partitions can be used to identify processes which may be dynamically reconfigured in the event of a fault. These methods should be of use in the design of robust distributed systems.

Data methods in optometry Part 9: experimental design and analysis of variance

The key to the correct application of ANOVA is careful experimental design and matching the correct analysis to that design. The following points should therefore, be considered before designing any experiment: 1. In a single factor design, ensure that the factor is identified as a 'fixed' or 'random effect' factor. 2. In more complex designs, with more than one factor, there may be a mixture of fixed and random effect factors present, so ensure that each factor is clearly identified. 3. Where replicates can be grouped or blocked, the advantages of a randomised blocks design should be considered. There should be evidence, however, that blocking can sufficiently reduce the error variation to counter the loss of DF compared with a randomised design. 4. Where different treatments are applied sequentially to a patient, the advantages of a three-way design in which the different orders of the treatments are included as an 'effect' should be considered. 5. Combining different factors to make a more efficient experiment and to measure possible factor interactions should always be considered. 6. The effect of 'internal replication' should be taken into account in a factorial design in deciding the number of replications to be used. Where possible, each error term of the ANOVA should have at least 15 DF. 7. Consider carefully whether a particular factorial design can be considered to be a split-plot or a repeated measures design. If such a design is appropriate, consider how to continue the analysis bearing in mind the problem of using post hoc tests in this situation.

Teaching our children when to eat:how parental feeding practices inform the development of emotional eating-a longitudinal experimental design

Background: Emotional eating in children has been related to the consumption of energy-dense foods and obesity, but the development of emotional eating in young children is poorly understood. Objectives: We evaluated whether emotional eating can be induced in 5-7-y-old children in the laboratory and assessed whether parental use of overly controlling feeding practices at 3-5 y of age predicts a greater subsequent tendency for children to eat under conditions of mild stress at ages 5-7 y. Design: Forty-one parent-child dyads were recruited to participate in this longitudinal study, which involved parents and children being observed consuming a standard lunch, completing questionnaire measures of parental feeding practices, participating in a research procedure to induce child emotion (or a control procedure), and observing children's consumption of snack foods. Results: Children at ages 5-7 y who were exposed to a mild emotional stressor consumed significantly more calories from snack foods in the absence of hunger than did children in a control group. Parents who reported the use of more food as a reward and restriction of food for health reasons with their children at ages 3-5 y were more likely to have children who ate more under conditions of negative emotion at ages 5-7 y. Conclusions: Parents who overly control children's food intake may unintentionally teach children to rely on palatable foods to cope with negative emotions. Additional research is needed to evaluate the implications of these findings for children's food intake and weight outside of the laboratory setting. This trial was registered at clinicaltrials.gov as NCT01122290.

The definition, theoretical modelling and empirical research of front-line service employee corporate identity within a UK national grocery retailer:determining the FLE corporate brand identification construct

Over the past forty years the corporate identity literature has developed to a point of maturity where it currently contains many definitions and models of the corporate identity construct at the organisational level. The literature has evolved by developing models of corporate identity or in considering corporate identity in relation to new and developing themes, e.g. corporate social responsibility. It has evolved into a multidisciplinary domain recently incorporating constructs from other literature to further its development. However, the literature has a number of limitations. It remains that an overarching and universally accepted definition of corporate identity is elusive, potentially leaving the construct with a lack of clear definition. Only a few corporate identity definitions and models, at the corporate level, have been empirically tested. The corporate identity construct is overwhelmingly defined and theoretically constructed at the corporate level, leaving the literature without a detailed understanding of its influence at an individual stakeholder level. Front-line service employees (FLEs), form a component in a number of corporate identity models developed at the organisational level. FLEs deliver the services of an organisation to its customers, as well as represent the organisation by communicating and transporting its core defining characteristics to customers through continual customer contact and interaction. This person-to-person contact between an FLE and the customer is termed a service encounter, where service encounters influence a customer’s perception of both the service delivered and the associated level of service quality. Therefore this study for the first time defines, theoretically models and empirically tests corporate identity at the individual FLE level, termed FLE corporate identity. The study uses the services marketing literature to characterise an FLE’s operating environment, arriving at five potential dimensions to the FLE corporate identity construct. These are scrutinised against existing corporate identity definitions and models to arrive at a definition for the construct. In reviewing the corporate identity, services marketing, branding and organisational psychology literature, a theoretical model is developed for FLE corporate identity, which is empirically and quantitatively tested, with FLEs in seven stores of a major national retailer. Following rigorous construct reliability and validity testing, the 601 usable responses are used to estimate a confirmatory factor analysis and structural equation model for the study. The results for the individual hypotheses and the structural model are very encouraging, as they fit the data well and support a definition of FLE corporate identity. This study makes contributions to the branding, services marketing and organisational psychology literature, but its principal contribution is to extend the corporate identity literature into a new area of discourse and research, that of FLE corporate identity

Senior management leadership, social support, job design and stressor-to-strain relationships in hospital practice

Purpose: The purpose of this paper is to examine the effect of the quality of senior management leadership on social support and job design, whose main effects on strains, and moderating effects on work stressors-to-strains relationships were assessed. Design/methodology/approach: A survey involving distribution of questionnaires was carried out on a random sample of health care employees in acute hospital practice in the UK. The sample comprised 65,142 respondents. The work stressors tested were quantitative overload and hostile environment, whereas strains were measured through job satisfaction and turnover intentions. Structural equation modelling and moderated regression analyses were used in the analysis. Findings: Quality of senior management leadership explained 75 per cent and 94 per cent of the variance of social support and job design respectively, whereas work stressors explained 51 per cent of the variance of strains. Social support and job design predicted job satisfaction and turnover intentions, as well as moderated significantly the relationships between quantitative workload/hostility and job satisfaction/turnover intentions. Research limitations/implications: The findings are useful to management and to health employees working in acute/specialist hospitals. Further research could be done in other counties to take into account cultural differences and variations in health systems. The limitations included self-reported data and percept-percept bias due to same source data collection. Practical implications: The quality of senior management leaders in hospitals has an impact on the social environment, the support given to health employees, their job design, as well as work stressors and strains perceived. Originality/value: The study argues in favour of effective senior management leadership of hospitals, as well as ensuring adequate support structures and job design. The findings may be useful to health policy makers and human resources managers. © Emerald Group Publishing Limited.

Entrepreneurial intentions in developing and developed countries

Purpose – This study proposes to use the Theory of Planned Behaviour to predict entrepreneurial intentions among students in five developing and nine developed countries. The purpose is to investigate whether entrepreneurial intention and its antecedents differ between developing and developed countries, and to test the theory in the two groups of countries. Design/methodology/approach – A total of 2,225 students in 13 countries participated in this study by responding to a structured questionnaire in classrooms. Structural equation modelling was used to analyse the data. Findings – The findings indicate that respondents from developing countries have stronger entrepreneurial intentions than those from developed countries. Moreover, the respondents from developing countries also score higher on the theory's antecedents of entrepreneurial intentions – attitudes, subjective norms, and perceived behavioural control – than respondents from developed countries. The findings support the Theory of Planned Behaviour in both developing and developed countries. Research limitations/implications – The findings strongly support the Theory of Planned Behaviour. The measure of subjective norms used, a multiple-item index encompassing the views of other people and motivation to comply with these, seems to have advantages over other measures of this concept. Practical implications – Developing countries need to focus on the development of institutions that can support entrepreneurial efforts. At the same time, developed economies may need to accept that entrepreneurial intentions are dependent on the dynamism of an economic environment and possibly on risk-perceiving behaviours. Originality/value – While multiple-country studies on entrepreneurship in developing and developed countries have been called for, no previous study has compared entrepreneurial intentions between developing and developed countries. The inclusion of developing countries provides a unique quasi-experimental setting in which to test the theory.

Sales manager and sales team determinants of salesperson ethical behaviour

Purpose – The purpose of this paper is to develop and test a model of the role managers and peers play in shaping salespeople's ethical behaviour. The model specifies that sales manager personal moral philosophies, whether sales managers themselves are rewarded according to the outcomes or behaviours of their salespeople, sales team job security, intra-team cooperation, and sales team tactical performance all influence sales team ethical standards. In turn, ethical standards influence the probability that sales team members will behave (un)ethically when faced with ethical dilemmas. Design/methodology/approach – The model is tested on a sample of 154 Finnish sales managers. Data were collected via mail survey. Analysis was undertaken using structural equation modelling. Findings – Ethical standards appear to be shaped by several factors; behaviour-based management controls increase ethical standards, relativist managers tend to manage less ethically-minded sales teams, job insecurity impedes the development of ethical standards, and sales teams' cooperation activity increases ethical standards. Sales teams are less likely to engage in unethical behaviour when the teams have strong ethical standards. Research limitations/implications – Cross-sectional data limits generalisability; single country data may limit the ability to generalise to different sales environments; additional measure development is needed; identification of additional antecedent factors would be beneficial. Practical implications – Sales managers should consciously develop high ethical standards in sales teams if they wish to reduce unethical behaviour. Ethical standards can be improved if sales managers change their own outward behaviour (exhibit a less relativistic ethical philosophy), foster cooperation amongst salespeople, and develop perceptions of job security. How sales managers are rewarded may shape how they approach the management of ethical behaviour in their sales teams. Originality/value – This paper appears to be the first to simultaneously examine both sales manager-specific and sales team-specific antecedents to sales team ethical standards and behaviours. As such, it provides an important base for research in this critical area.

Individual spirit at work and its relationship with employee work attitudes and organisational outcomes:An empirical examination in corporate Thailand

The purpose of this thesis is to conduct empirical research in corporate Thailand in order to (1) validate the Spirit at Work Scale (2) investigate the relationships between individual spirit at work and three employee work attitudinal variables (job satisfaction, organisational identification and psychological well-being) and three organisational outcomes (in-role performance, organisational citizenship behaviours (OCB), and turnover intentions) (3) further examine causal relations among these organisational behaviour variables with a longitudinal design (4) examine three employee work attitudes as mediator variables between individual spirit at work and three organisational outcomes and (5) explore the potential antecedents of organisational conditions that foster employee experienced individual spirit at work. The two pilot studies with 155 UK and 175, 715 Thai samples were conducted for validation testing of the main measure used in this study: Spirit at Work Scale (Kinjerski & Skrypnek, 2006a). The results of the two studies including discriminant validity analyses strongly provided supportive evidence that Spirit at Work Scale (SAWS) is a sound psychometric measure and also a distinct construct from the three work attitude constructs. The final model of SAWS contains a total of twelve items; a three factor structure (meaning in work, sense of community, and spiritual connection) in which the sub-factors loaded on higher order factors and also had very acceptable reliability. In line with these results it was decided to use the second-order of SAWS model for Thai samples in the main study and subsequent analysis. The 715 completed questionnaires were received from the first wave of data collection during July - August 2008 and the second wave was conducted again within the same organisations and 501 completed questionnaires were received during March - April 2009. Data were obtained through 49 organisations which were from three types of organisations within Thailand: public organisations, for-profit organisations, and notfor-profit organisations. Confirmatory factor analysis of all measures used in the study and hypothesised model were tested with structural equation modelling techniques. The results were greatly supportive for the direct structural model and partially supportive for the fully mediated model. Moreover, there were different findings across self report and supervisor rating on performance and OCB models. Additionally, the antecedent conditions that fostered employees experienced individual spirit at work and the implications of these findings for research and practice are discussed.

The impacts of market orientation and corporate social responsibility on firm performance:evidence from China

Purpose – The purpose of this paper is to investigate the joint effects of market orientation (MO) and corporate social responsibility (CSR) on firm performance. Design/methodology/approach – Data were collected via a questionnaire survey of star-rated hotels in China and a total of 143 valid responses were received. The hypotheses were tested by employing structural equation modelling with a maximum likelihood estimation option. Findings – It was found that although both MO and CSR could enhance performance, once the effects of CSR are accounted for, the direct effects of MO on performance diminish considerably to almost non-existent. Although this result may be due to the fact that the research is conducted in China, a country where CSR might be crucially important to performance given the country's socialist legacy, it nonetheless provides strong evidence that MO's impact on organizational performance is mediated by CSR. Research limitations/implications – The main limitations include the use of cross-sectional data, the subjective measurement of performance and the uniqueness of the research setting (China). The findings provide an additional important insight into the processes by which a market oriented culture is transformed into superior organizational performance. Originality/value – This paper is one of the first to examine the joint effects of MO and CSR on business performance. The empirical evidence from China adds to the existing literature on the respective importance of MO and CSR.

Gas distribution in shallow packed beds

Packed beds have many industrial applications and are increasingly used in the process industries due to their low pressure drop. With the introduction of more efficient packings, novel packing materials (i.e. adsorbents) and new applications (i.e. flue gas desulphurisation); the aspect ratio (height to diameter) of such beds is decreasing. Obtaining uniform gas distribution in such beds is of crucial importance in minimising operating costs and optimising plant performance. Since to some extent a packed bed acts as its own distributor the importance of obtaining uniform gas distribution has increased as aspect ratios (bed height to diameter) decrease. There is no rigorous design method for distributors due to a limited understanding of the fluid flow phenomena and in particular of the effect of the bed base / free fluid interface. This study is based on a combined theoretical and modelling approach. The starting point is the Ergun Equation which is used to determine the pressure drop over a bed where the flow is uni-directional. This equation has been applied in a vectorial form so it can be applied to maldistributed and multi-directional flows and has been realised in the Computational Fluid Dynamics code PHOENICS. The use of this equation and its application has been verified by modelling experimental measurements of maldistributed gas flows, where there is no free fluid / bed base interface. A novel, two-dimensional experiment has been designed to investigate the fluid mechanics of maldistributed gas flows in shallow packed beds. The flow through the outlet of the duct below the bed can be controlled, permitting a rigorous investigation. The results from this apparatus provide useful insights into the fluid mechanics of flow in and around a shallow packed bed and show the critical effect of the bed base. The PHOENICS/vectorial Ergun Equation model has been adapted to model this situation. The model has been improved by the inclusion of spatial voidage variations in the bed and the prescription of a novel bed base boundary condition. This boundary condition is based on the logarithmic law for velocities near walls without restricting the velocity at the bed base to zero and is applied within a turbulence model. The flow in a curved bed section, which is three-dimensional in nature, is examined experimentally. The effect of the walls and the changes in gas direction on the gas flow are shown to be particularly significant. As before, the relative amounts of gas flowing through the bed and duct outlet can be controlled. The model and improved understanding of the underlying physical phenomena form the basis for the development of new distributors and rigorous design methods for them.

Drying processess in the United Kingdom:assessment of industrial energy utilisation and efficiency of drying systems and the modelling of drying characters using neural networks (BL)

Drying is an important unit operation in process industry. Results have suggested that the energy used for drying has increased from 12% in 1978 to 18% of the total energy used in 1990. A literature survey of previous studies regarding overall drying energy consumption has demonstrated that there is little continuity of methods and energy trends could not be established. In the ceramics, timber and paper industrial sectors specific energy consumption and energy trends have been investigated by auditing drying equipment. Ceramic products examined have included tableware, tiles, sanitaryware, electrical ceramics, plasterboard, refractories, bricks and abrasives. Data from industry has shown that drying energy has not varied significantly in the ceramics sector over the last decade, representing about 31% of the total energy consumed. Information from the timber industry has established that radical changes have occurred over the last 20 years, both in terms of equipment and energy utilisation. The energy efficiency of hardwood drying has improved by 15% since the 1970s, although no significant savings have been realised for softwood. A survey estimating the energy efficiency and operating characteristics of 192 paper dryer sections has been conducted. Drying energy was found to increase to nearly 60% of the total energy used in the early 1980s, but has fallen over the last decade, representing 23% of the total in 1993. These results have demonstrated that effective energy saving measures, such as improved pressing and heat recovery, have been successfully implemented since the 1970s. Artificial neural networks have successfully been applied to model process characteristics of microwave and convective drying of paper coated gypsum cove. Parameters modelled have included product moisture loss, core gypsum temperature and quality factors relating to paper burning and bubbling defects. Evaluation of thermal and dielectric properties have highlighted gypsum's heat sensitive characteristics in convective and electromagnetic regimes. Modelling experimental data has shown that the networks were capable of simulating drying process characteristics to a high degree of accuracy. Product weight and temperature were predicted to within 0.5% and 5C of the target data respectively. Furthermore, it was demonstrated that the underlying properties of the data could be predicted through a high level of input noise.