Heterodimers and family-B GPCRs:RAMPs, CGRP and adrenomedullin

RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, allowing the generation of six distinct receptors with preferences for CGRP (CT gene-related peptide) adrenomedullin, amylin and CT. There are three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of receptor pharmacology whereas the transmembrane domain contributes to association of the RAMP with the GPCR. The N-terminus of all members of the RAMP family probably contains two disulphide bonds; a potential third disulphide is found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the ligand and plays a key role in its binding, either directly or indirectly. BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very high selectivity for the human CGRP(1) receptor.

The TAP approach to intensive and extensive connectivity systems

The Thouless-Anderson-Palmer (TAP) approach was originally developed for analysing the Sherrington-Kirkpatrick model in the study of spin glass models and has been employed since then mainly in the context of extensively connected systems whereby each dynamical variable interacts weakly with the others. Recently, we extended this method for handling general intensively connected systems where each variable has only O(1) connections characterised by strong couplings. However, the new formulation looks quite different with respect to existing analyses and it is only natural to question whether it actually reproduces known results for systems of extensive connectivity. In this chapter, we apply our formulation of the TAP approach to an extensively connected system, the Hopfield associative memory model, showing that it produces identical results to those obtained by the conventional formulation.

To reveal is to critique:actor-network theory and critical information systems research

It has been suggested that, in order to maintain its relevance, critical research must develop a strong emphasis on empirical work rather than the conceptual emphasis that has typically characterized critical scholarship in management. A critical project of this nature is applicable in the information systems (IS) arena, which has a growing tradition of qualitative inquiry. Despite its relativist ontology, actor–network theory places a strong emphasis on empirical inquiry and this paper argues that actor–network theory, with its careful tracing and recording of heterogeneous networks, is well suited to the generation of detailed and contextual empirical knowledge about IS. The intention in this paper is to explore the relevance of IS research informed by actor–network theory in the pursuit of a broader critical research project as de? ned in earlier work.

Q parameter estimation using numerical simulations for linear and nonlinear transmission systems

We compare the Q parameter obtained from scalar, semi-analytical and full vector models for realistic transmission systems. One set of systems is operated in the linear regime, while another is using solitons at high peak power. We report in detail on the different results obtained for the same system using different models. Polarisation mode dispersion is also taken into account and a novel method to average Q parameters over several independent simulation runs is described. © 2006 Elsevier B.V. All rights reserved.

Semi-analytical Q parameter estimate in linear and nonlinear transmission systems

We compare the Q parameter obtained from the semi-analytical model with scalar and vector models for two realistic transmission systems. First a linear system with a compensated dispersion map and second a soliton transmission system.

Biomass-based small and micro combined heat and power (CHP) systems:application and status in the United Kingdom

This chapter discusses the current state of biomass-based combined heat and power (CHP) production in the UK. It presents an overview of the UK's energy policy and targets which are relevant to the deployment of biomass-based CHP and summarises the current state for renewable, biomass and CHP. A number of small-scale biomass-based CHP projects are described while providing some indicative capital costs for combustion, pyrolysis and gasification technologies. For comparison purposes, it presents an overview of the respective situation in Europe and particularly in Sweden, Finland and Denmark. There is also a brief comment about novel CHP technologies in Austria. Finally it draws some conclusions on the potential of small-scale biomass CHP in the UK. © 2011 Woodhead Publishing Limited All rights reserved.

A systems methodology for analysing and simulating manufacturing systems

The Systems Engineering Group (SEG) at De Montfort University are developing the Boardman Soft Systems Methodology (BSSM) which allows complex human systems to be modelled, this work builds upon Checkland's Soft Systems Methodology (1981). The BSSM has been applied to the modelling of the systems engineering process as used in design and manufacturing companies. The BSSM is used to solicit information from a company and this data is then transformed into systemic diagrams (systemigrams). These systemigrams are posited to be accurate and concise representations of the system which has been modelled. This paper describes the collaboration between SEG and a manufacturing company (MC) in Leicester, England. The purpose of this collaboration was twofold. First, it was to create an objective view of the MC's processes, in the form of systemigrams. It was important to get this modelled by a source outside of the company, as it is difficult for people within a system being modelled to be unbiased. Secondly, it allowed a series of systemigrams to be produced which can then be subjected to simulation, for the purpose of aiding risk management decisions and to reduce the project cycle time

Canonical solution groups of a homomorphism : manipulator kinematics, nonparametric regression and distributed object systems

The kinematic mapping of a rigid open-link manipulator is a homomorphism between Lie groups. The homomorphisrn has solution groups that act on an inverse kinematic solution element. A canonical representation of solution group operators that act on a solution element of three and seven degree-of-freedom (do!) dextrous manipulators is determined by geometric analysis. Seven canonical solution groups are determined for the seven do! Robotics Research K-1207 and Hollerbach arms. The solution element of a dextrous manipulator is a collection of trivial fibre bundles with solution fibres homotopic to the Torus. If fibre solutions are parameterised by a scalar, a direct inverse funct.ion that maps the scalar and Cartesian base space coordinates to solution element fibre coordinates may be defined. A direct inverse pararneterisation of a solution element may be approximated by a local linear map generated by an inverse augmented Jacobian correction of a linear interpolation. The action of canonical solution group operators on a local linear approximation of the solution element of inverse kinematics of dextrous manipulators generates cyclical solutions. The solution representation is proposed as a model of inverse kinematic transformations in primate nervous systems. Simultaneous calibration of a composition of stereo-camera and manipulator kinematic models is under-determined by equi-output parameter groups in the composition of stereo-camera and Denavit Hartenberg (DH) rnodels. An error measure for simultaneous calibration of a composition of models is derived and parameter subsets with no equi-output groups are determined by numerical experiments to simultaneously calibrate the composition of homogeneous or pan-tilt stereo-camera with DH models. For acceleration of exact Newton second-order re-calibration of DH parameters after a sequential calibration of stereo-camera and DH parameters, an optimal numerical evaluation of DH matrix first order and second order error derivatives with respect to a re-calibration error function is derived, implemented and tested. A distributed object environment for point and click image-based tele-command of manipulators and stereo-cameras is specified and implemented that supports rapid prototyping of numerical experiments in distributed system control. The environment is validated by a hierarchical k-fold cross validated calibration to Cartesian space of a radial basis function regression correction of an affine stereo model. Basic design and performance requirements are defined for scalable virtual micro-kernels that broker inter-Java-virtual-machine remote method invocations between components of secure manageable fault-tolerant open distributed agile Total Quality Managed ISO 9000+ conformant Just in Time manufacturing systems.

A study of the effect of harmonics in the system on the performance of residual current-operated circuit-breakers and electromechanical overcurrent relays

Residual current-operated circuit-breakers (RCCBs) have proved useful devices for the protection of both human beings against ventricular fibrillation and installations against fire. Although they work well with sinusoidal waveforms, there is little published information on their characteristics. Due to shunt connected non-linear devices, not the least of which is the use of power electronic equipment, the supply is distorted. Consequently, RCCBs as well as other protection relays are subject to non-sinusoidal current waveforms. Recent studies showed that RCCBs are greatly affected by harmonics, however the reasons for this are not clear. A literature search has also shown that there are inconsistencies in the analysis of the effect of harmonics on protection relays. In this work, the way RCCBs operate is examined, then a model is built with the aim of assessing the effect of non-sinusoidal current on RCCBs. Tests are then carried out on a number of RCCBs and these, when compared with the results from the model showed good correlation. In addition, the model also enables us to explain the RCCBs characteristics for pure sinusoidal current. In the model developed, various parameters are evaluated but special attention is paid to the instantaneous value of the current and the tripping mechanism movement. A similar assessment method is then used to assess the effect of harmonics on two types of protection relay, the electromechanical instantaneous relay and time overcurrent relay. A model is built for each of them which is then simulated on the computer. Tests results compare well with the simulation results, and thus the model developed can be used to explain the relays behaviour in a harmonics environment. The author's models, analysis and tests show that RCCBs and protection relays are affected by harmonics in a way determined by the waveform and the relay constants. The method developed provides a useful tool and the basic methodology to analyse the behaviour of RCCBs and protection relays in a harmonics environment. These results have many implications, especially the way RCCBs and relays should be tested if harmonics are taken into account.

Mild wear in dry and lubricated sliding systems

A vertical pin on horizontal disc machine has been used to conduct a series of experiments in air under dry and lubricating sliding conditions. For dry sliding low load and speed combinations were chosen to correspond to the mild wear region below the Welsh T1 transition. Lubricated tests were conducted under flooded conditions using Esso Technical White Oil alone and with a 0.1% stearic acid additive, for load and speed ranges that produced substantial amounts of asperity contact and thus a boundary lubricated regime of wear. The test material in all cases was AISI 52100 steel, for unlubricated sliding subjected to loads from 5 to 50 N and a range of speeds from 10-3 to 1.0 ms-1, and for lubricated sliding loads of 50 to 123 N and for speeds of 10-2 to 1.0 ms-1. Unlubricated wear debris was found to be a mixture of -Fe_2O_3 and -Fe. Unlubricated wear was found to occur via a thin film logarithmic oxide growth followed by agglomeration into thicker oxide plateaux 2 to 10 m in thickness. Lubricated wear occurred via thick film diffusion controlled oxide growth producing homogeneous oxide plateaux 0.1 to 0.2 m in thickness. X-ray photoelectron spectroscopy identified the presence of a surface film on pins worn in White Oil with stearic acid, which is thought to be iron stearate. A model has been developed for unlubricated wear based upon the postulated growth of thin film oxides by a logarithmic rate law. The importance of sliding geometry and environment to the dominant wear mechanism has been illustrated.

Strategic development process and complex adaptive systems

The two areas of theory upon which this research was based were „strategy development process?(SDP) and „complex adaptive systems? (CAS), as part of complexity theory, focused on human social organisations. The literature reviewed showed that there is a paucity of empirical work and theory in the overlap of the two areas, providing an opportunity for contributions to knowledge in each area of theory, and for practitioners. An inductive approach was adopted for this research, in an effort to discover new insights to the focus area of study. It was undertaken from within an interpretivist paradigm, and based on a novel conceptual framework. The organisationally intimate nature of the research topic, and the researcher?s circumstances required a research design that was both in-depth and long term. The result was a single, exploratory, case study, which included use of data from 44 in-depth, semi-structured interviews, from 36 people, involving all the top management team members and significant other staff members; observations, rumour and grapevine (ORG) data; and archive data, over a 5½ year period (2005 – 2010). Findings confirm the validity of the conceptual framework, and that complex adaptive systems theory has potential to extend strategy development process theory. It has shown how and why the strategy process developed in the case study organisation by providing deeper insights to the behaviour of the people, their backgrounds, and interactions. Broad predictions of the „latent strategy development? process and some elements of the strategy content are also possible. Based on this research, it is possible to extend the utility of the SDP model by including peoples? behavioural characteristics within the organisation, via complex adaptive systems theory. Further research is recommended to test limits of the application of the conceptual framework and improve its efficacy with more organisations across a variety of sectors.

A comparison of U.S. and Japanese management systems and their transferability to Singapore industry

This research compares U.S. and Japanese management systems and evaluates their transferability to the Singaporean manufacturing industry. The objectives were:- a) To determine the effectiveness of U.S. and Japanese management systems when applied to Singapore. b) Determine the extent of transferability of U.S. and Japanese management systems to Singapore. c) Survey general problems ecountered in the application of U.S. and Japanese management systems to the Singapore industry. The study using questionnaire survey and interviews covered a total of eighty companies from four groups of firms in four industrial sectors comprising of U.S. and Japanese subsidiaries based in Singapore and their respective parent companies. Data from the questionnaires and interviews were used to investigate environmental conditions, management philosophy, management functions/practices, management effectiveness, and firm productivity. Two-way analysis of variance was used to analyse the questionnaire data. The analysis of the perceptual data from the questionnaire survey and interviews suggested that both U.S. and Japanese parent companies performed better in almost all the management variables studied when compared to their subsidiaries in Singapore. U.S. subsidiaries have less difficulty in adjusting to the Singapore environmental conditions and obtained better results than the Japanese subsidiaries in management functions/practices and management philosophy than the U.S. subsidiaries. In addition, the firm productivity (in terms of labour and capital productivity) of U.S. subsidiaries in Singapore was found to be higher than those of the Japanese subsidiaries. It was found that the Japanese parent companies returned the highest score among the four groups of firms in all the four industrial sectors for all the four management variables (i.e. environmental conditions, management philosophy, management functions/practices, and management effectiveness) surveyed using questionnaires. In contrast, the average score for Japanese subsidiaries in Singapore was generally the lowest among the four groups of firms. Thus the results of this study suggest that the transfer of U.S. management system into the Singapore industry is more successful than the Japanese management system. The problems encountered in the application of U.S. and Japanese management in Singapore were identified and discussed by the study. General recommendations for the Singaporean manufacturing industry were then made based on the findings of the questionnaire survey and interview analysis.

Alginates as therapeutic and drug delivery systems

Alginate is widely used as a viscosity enhancer in many different pharmaceutical formulations. The aim of this thesis is to quantitatively describe the functions of this polyelectrolyte in pharmaceutical systems. To do this the techniques used were Viscometry, Light Scattering, Continuous and Oscillatory Shear Rheometry, Numerical Analysis and Diffusion. Molecular characterization of the Alginate was carried out using Viscometry and Light Scattering to determine the molecular weight, the radius of gyration, the second virial coefficient and the Kuhn statistical segment length. The results showed good agreement with similar parameters obtained in previous studies. By blending Alginate with other polyelectrolytes, Xanthan Gum and 'Carbopol', in various proportions and with various methods of low and high shear preparation, a very wide range of dynamic rheological properties was found. Using oscillatory testing, the parameters often varied over several decades of magnitude. It was shown that the determination of the viscous and elastic components is particularly useful in describing the rheological 'profiles' of suspending agent blends and provides a step towards the non-empirical formulation of pharmaceutical disperse systems. Using numerical analysis of equations describing planar diffusion, it was shown that the analysis of drug release profiles alone does not provide unambiguous information about the mechanism of rate control. These principles were applied to the diffusion of Ibuprofen in Calcium Alginate gels. For diffusion in such non-Newtonian systems, emphasis was placed on the use of the elastic as well as the viscous component of viscoelasticity. It was found that the diffusion coefficients were relatively unaffected by increases in polymer concentration up to 5 per cent, yet the elasticities measured by oscillatory shear rheometry were increased. This was interpreted in the light of several theories of diffusion in gels.