Modulation of certain 5-HT-related behaviours by serotonergic and noradrenergic systems

The modulation of 5-hydroxytryptamine (5-HT)-related head-twitchbehaviour by antimigraine drugs and migraine triggers was examined inmice. The antimigraine drugs examined produced either inhibition or noeffect on 5-HT-related head-twitching. On the basis of these resultsit is suggested that 5-HT-related head-twitching is unlikely to beuseful in the preclinical screening and discovery of systemically-activeantimigraine agents. The migraine triggers examined, tyramineand beta-PEA initially produced a repeatable complex time-relatedeffect on 5-HT-related head-twitching, with both inhibition andpotentiation of this behaviour being observed, however, when furtherexamination of the effect of the migraine triggers on 5-HT-relatedhead-twitching was attempted some time later the effects seeninitially were no longer produced. The effect of (±)-1-<2, 5-dimethoxy-4-iodophenyl)-2-aminopropane,((±)DOl), on on-going behaviour of mice and rats was examined. Shakingbehaviour was observed in both species. In mice, excessive scratchingbehaviour was also present. (±)DOl-induced scratching and shakingbehaviour were found to be differentially modulated by noradrenergicand serotonergic agents, however, the fact that both behaviours wereblocked by ritanserin (5-HT2/5-HT1c receptor antagonist) and inhibitedby FLA-63 (a dopamine-beta-oxidase inhibitor which depletesnoradrenaline), suggests the pathways mediating these behaviours mustbe convergent in some manner, and that both behaviours require intact5-HT receptors, probably 5-HT2 receptors, for their production. Ingeneral, the behavioural profile of (±)DOI was as expected for anagent which exhibits high affinity binding to 5-HT2/5-HT1c receptors.Little sign of the 5-HTl-related '5-HT syndrome' was seen in eithermice or rats. The effect of a variety of noradrenergic agents on head-twitchinginduced by a variety of shake-inducing agents was examined. A patternof modulatory effect was seen whereby the modulatory effect of thenoradrenergic agents on 5-hydroxytryptophan <5-HTP) (and in some cases, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)) was found to be the opposite of that observed with quipazine and (±)DOI. The relationship between these effects, and their implications for understanding the pharmacology of centrally acting drugs is discussed.

Modelling manufacturing planning and control systems:the application of object-oriented principles and discrete-event simulation

Manufacturing planning and control systems are fundamental to the successful operations of a manufacturing organisation. 10 order to improve their business performance, significant investment is made by companies into planning and control systems; however, not all companies realise the benefits sought Many companies continue to suffer from high levels of inventory, shortages, obsolete parts, poor resource utilisation and poor delivery performance. This thesis argues that the fit between the planning and control system and the manufacturing organisation is a crucial element of success. The design of appropriate control systems is, therefore, important. The different approaches to the design of manufacturing planning and control systems are investigated. It is concluded that there is no provision within these design methodologies to properly assess the impact of a proposed design on the manufacturing facility. Consequently, an understanding of how a new (or modified) planning and control system will perform in the context of the complete manufacturing system is unlikely to be gained until after the system has been implemented and is running. There are many modelling techniques available, however discrete-event simulation is unique in its ability to model the complex dynamics inherent in manufacturing systems, of which the planning and control system is an integral component. The existing application of simulation to manufacturing control system issues is limited: although operational issues are addressed, application to the more fundamental design of control systems is rarely, if at all, considered. The lack of a suitable simulation-based modelling tool does not help matters. The requirements of a simulation tool capable of modelling a host of different planning and control systems is presented. It is argued that only through the application of object-oriented principles can these extensive requirements be achieved. This thesis reports on the development of an extensible class library called WBS/Control, which is based on object-oriented principles and discrete-event simulation. The functionality, both current and future, offered by WBS/Control means that different planning and control systems can be modelled: not only the more standard implementations but also hybrid systems and new designs. The flexibility implicit in the development of WBS/Control supports its application to design and operational issues. WBS/Control wholly integrates with an existing manufacturing simulator to provide a more complete modelling environment.

Exploratory data analysis with non-linear and missing data in geochemistry

Exploratory analysis of data seeks to find common patterns to gain insights into the structure and distribution of the data. In geochemistry it is a valuable means to gain insights into the complicated processes making up a petroleum system. Typically linear visualisation methods like principal components analysis, linked plots, or brushing are used. These methods can not directly be employed when dealing with missing data and they struggle to capture global non-linear structures in the data, however they can do so locally. This thesis discusses a complementary approach based on a non-linear probabilistic model. The generative topographic mapping (GTM) enables the visualisation of the effects of very many variables on a single plot, which is able to incorporate more structure than a two dimensional principal components plot. The model can deal with uncertainty, missing data and allows for the exploration of the non-linear structure in the data. In this thesis a novel approach to initialise the GTM with arbitrary projections is developed. This makes it possible to combine GTM with algorithms like Isomap and fit complex non-linear structure like the Swiss-roll. Another novel extension is the incorporation of prior knowledge about the structure of the covariance matrix. This extension greatly enhances the modelling capabilities of the algorithm resulting in better fit to the data and better imputation capabilities for missing data. Additionally an extensive benchmark study of the missing data imputation capabilities of GTM is performed. Further a novel approach, based on missing data, will be introduced to benchmark the fit of probabilistic visualisation algorithms on unlabelled data. Finally the work is complemented by evaluating the algorithms on real-life datasets from geochemical projects.

Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces:state versus trait vulnerability markers of depression in bipolar disorder

Background - Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Methods - Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results - The BD versus HC showed significantly greater right amygdala-OFC FC (p = .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). Conclusions - In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC–FA relationships in BD and HC require further study.

Forecasting the UK/US exchange rate with divisia monetary models and neural networks

This paper compares the UK/US exchange rate forecasting performance of linear and nonlinear models based on monetary fundamentals, to a random walk (RW) model. Structural breaks are identified and taken into account. The exchange rate forecasting framework is also used for assessing the relative merits of the official Simple Sum and the weighted Divisia measures of money. Overall, there are four main findings. First, the majority of the models with fundamentals are able to beat the RW model in forecasting the UK/US exchange rate. Second, the most accurate forecasts of the UK/US exchange rate are obtained with a nonlinear model. Third, taking into account structural breaks reveals that the Divisia aggregate performs better than its Simple Sum counterpart. Finally, Divisia-based models provide more accurate forecasts than Simple Sum-based models provided they are constructed within a nonlinear framework.

Attachment anxiety and friendship group identification under attachment threat:the moderating role of priming support network expectations

We examined the role of priming participants' own network expectations on their subsequent identification with their friendship group. We examined this prime alongside attachment anxiety and attachment threat, as predictors of friendship group identification. Previous research has suggested that attachment anxiety is associated with negative network expectations. In this study, we extended this work to show that when a network expectation prime was absent, higher attachment anxiety was associated with lower group identification under attachment threat, compared to a control condition. However, when expectations of support network were primed, attachment threat no longer affected group identification, so that only attachment anxiety predicted group identification. This suggests that priming participants who are high in attachment anxiety with their own network expectancies (which are negative), results in participants dis-identifying with their friendship group, regardless of whether or not they have experienced attachment threat. © 2012 Elsevier Ltd.

Reliability monitoring, feedback and improvement systems:their application in the machine tool industry

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Compensating for dispersion and nonlinear Kerr effect without phase conjugation

We propose the use of a dispersive medium with a negative nonlinear refractive-index coefficient as a way to compensate for the dispersion and the nonlinear effects resulting from pulse propagation in an optical fiber. The undoing of pulse interaction might allow for increased bit rates.

The analogue computer simulation of integrated chemical plant and controller systems

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Managing enterprises and ERP systems:a contingency model for the enterprization of operations

Purpose: The purpose of this paper is to investigate enterprise resource planning (ERP) systems development and emerging practices in the management of enterprises (i.e. parts of companies working with parts of other companies to deliver a complex product and/or service) and identify any apparent correlations. Suitable a priori contingency frameworks are then used and extended to explain apparent correlations. Discussion is given to provide guidance for researchers and practitioners to deliver better strategic, structural and operational competitive advantage through this approach; coined here as the "enterprization of operations". Design/methodology/approach: Theoretical induction uses a new empirical longitudinal case study from Zoomlion (a Chinese manufacturing company) built using an adapted form of template analysis to produce a new contingency framework. Findings: Three main types of enterprises and the three main types of ERP systems are defined and correlations between them are explained. Two relevant a priori frameworks are used to induct a new contingency model to support the enterprization of operations; known as the dynamic enterprise reference grid for ERP (DERG-ERP). Research limitations/implications: The findings are based on one longitudinal case study. Further case studies are currently being conducted in the UK and China. Practical implications: The new contingency model, the DERG-ERP, serves as a guide for ERP vendors, information systems management and operations managers hoping to grow and sustain their competitive advantage with respect to effective enterprise strategy, enterprise structure and ERP systems. Originality/value: This research explains how ERP systems and the effective management of enterprises should develop in order to sustain competitive advantage with respect to enterprise strategy, enterprise structure and ERP systems use. © Emerald Group Publishing Limited.

Span design for reduced noise and nonlinear impairments in a dispersion-managed Raman amplified system

We study a periodic Raman amplified dispersion-managed system with backward-pumping configuration, considering noise and nonlinear impairments. A general optimization method based on nonlinearity management is applied in order to find the configuration that maximizes the system performance. The system is later tested using a full numerical implementation of the nonlinear Schrödinger equation and shown to effectively deliver its longest propagation distance in the same optimal region.

MEG and complex systems

MEG beamformer algorithms work by making the assumption that correlated and spatially distinct local field potentials do not develop in the human brain. Despite this assumption, images produced by such algorithms concur with those from other non-invasive and invasive estimates of brain function. In this paper we set out to develop a method that could be applied to raw MEG data to explicitly test his assumption. We show that a promax rotation of MEG channel data can be used as an approximate estimator of the number of spatially distinct correlated sources in any frequency band.