22 resultados para whether magistrate may order that parties be legally represented in QCAT
em Aston University Research Archive
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This thesis examines the possibility of privatising public owned five star hotels in Egypt through its stock market in order to give a boost to the Egyptian privatisation programme and to help activate its stock market. To explore these aspects, two main technical exercises were executed. First the writer constructed, for the first time in Egypt, a daily price index for Cairo Stock Exchange and an index for the tourism sector, in order to analyze the efficiency of the capital market. This technical analysis showed that Cairo stock exchange is inefficient, stagnant and undergoes minimal fluctuations, especially when compared to other developed and emerging markets. Second, given the importance and complexity of the valuation of SOEs prior to their privatisation, a sample of three five star hotels that could be prime candidates for privatisation via the stock market in Egypt were selected and a detailed financial analysis for the three hotels was concluded. The result was a valuation range for the three hotels using various valuation methods. Nevertheless it was found out that the final value of hotels will be determined by the market itself. Depite the inefficiency of Cairo Stock Exchange, the thesis did not rule out privatisation through the stock market. On the contrary it cited several examples of developing countries that were able to successfully privatise some of their SOEs via their rudimentary capital markets. Finally, the thesis recommended that five star hotels could be pefect candidates for privatisation via the stock market in Egypt. This is because five star hotels are profitable, privately managed, non strategic and not highly capital intensive businesses. In addition, they do not suffer from overstaffing and the industry in which they operate i.e. tourism sector, has high growth prospects and is of an international nature. Therefore it is anticipated that privatisation of five star hotels can attract a lot of investors because of the relatively high returns. This in turn will help activate and popularize the capital market in Egypt. At the same time the benefits of privatisation would be more visible which will give more momentum to the privatisation programme and make it more politically acceptable.
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INTRODUCTION: The inappropriate use of antipsychotics in people with dementia for behaviour that challenges is associated with an estimated 1800 deaths annually. However, solely focusing on antipsychotics may transfer prescribing to other equally dangerous psychotropics. Little is known about the role of pharmacists in the management of psychotropics used to treat behaviours that challenge. This research aims to determine whether it is feasible to implement and measure the effectiveness of a combined pharmacy-health psychology intervention incorporating a medication review and staff training package to limit the prescription of psychotropics to manage behaviour that challenges in care home residents with dementia. METHODS/ANALYSIS: 6 care homes within the West Midlands will be recruited. People with dementia receiving medication for behaviour that challenges, or their personal consultee, will be approached regarding participation. Medication used to treat behaviour that challenges will be reviewed by the pharmacist, in collaboration with the general practitioner (GP), person with dementia and carer. The behavioural intervention consists of a training package for care home staff and GPs promoting person-centred care and treating behaviours that challenge as an expression of unmet need. The primary outcome measure is the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Other outcomes include quality of life (EQ-5D and DEMQoL), cognition (sMMSE), health economic (CSRI) and prescribed medication including whether recommendations were implemented. Outcome data will be collected at 6 weeks, and 3 and 6 months. Pretraining and post-training interviews will explore stakeholders' expectations and experiences of the intervention. Data will be used to estimate the sample size for a definitive study. ETHICS/DISSEMINATION: The project has received a favourable opinion from the East Midlands REC (15/EM/3014). If potential participants lack capacity, a personal consultee will be consulted regarding participation in line with the Mental Capacity Act. Results will be published in peer-reviewed journals and presented at conferences.
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Practising engineers frequently seek to understand what the effects of various manufacturing strategies will be on the performance of their production facilities. In this situation a computer model can help to provide insight and form predictions about future manufacturing system performance. Various types of modelling methods exist and each provide models that have distinct characteristics. This paper presents a review of popular modelling techniques and, based on the results of a structured experimental study, summarises their capabilities to support the evaluation of manufacturing strategies.
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Requirements are sensitive to the context in which the system-to-be must operate. Where such context is well-understood and is static or evolves slowly, existing RE techniques can be made to work well. Increasingly, however, development projects are being challenged to build systems to operate in contexts that are volatile over short periods in ways that are imperfectly understood. Such systems need to be able to adapt to new environmental contexts dynamically, but the contextual uncertainty that demands this self-adaptive ability makes it hard to formulate, validate and manage their requirements. Different contexts may demand different requirements trade-offs. Unanticipated contexts may even lead to entirely new requirements. To help counter this uncertainty, we argue that requirements for self-adaptive systems should be run-time entities that can be reasoned over in order to understand the extent to which they are being satisfied and to support adaptation decisions that can take advantage of the systems' self-adaptive machinery. We take our inspiration from the fact that explicit, abstract representations of software architectures used to be considered design-time-only entities but computational reflection showed that architectural concerns could be represented at run-time too, helping systems to dynamically reconfigure themselves according to changing context. We propose to use analogous mechanisms to achieve requirements reflection. In this paper we discuss the ideas that support requirements reflection as a means to articulate some of the outstanding research challenges.
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In the field of mental health risk assessment, there is no standardisation between the data used in different systems. As a first step towards the possible interchange of data between assessment tools, an ontology has been constructed for a particular one, GRiST (Galatean Risk Screening Tool). We briefly introduce GRiST and its data structures, then describe the ontology and the benefits that have already been realised from the construction process. For example, the ontology has been used to check the consistency of the various trees used in the model. We then consider potential uses in integration of data from other sources. © 2009 IEEE.
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Full text: The idea of producing proteins from recombinant DNA hatched almost half a century ago. In his PhD thesis, Peter Lobban foresaw the prospect of inserting foreign DNA (from any source, including mammalian cells) into the genome of a λ phage in order to detect and recover protein products from Escherichia coli [ 1 and 2]. Only a few years later, in 1977, Herbert Boyer and his colleagues succeeded in the first ever expression of a peptide-coding gene in E. coli — they produced recombinant somatostatin [ 3] followed shortly after by human insulin. The field has advanced enormously since those early days and today recombinant proteins have become indispensable in advancing research and development in all fields of the life sciences. Structural biology, in particular, has benefitted tremendously from recombinant protein biotechnology, and an overwhelming proportion of the entries in the Protein Data Bank (PDB) are based on heterologously expressed proteins. Nonetheless, synthesizing, purifying and stabilizing recombinant proteins can still be thoroughly challenging. For example, the soluble proteome is organized to a large part into multicomponent complexes (in humans often comprising ten or more subunits), posing critical challenges for recombinant production. A third of all proteins in cells are located in the membrane, and pose special challenges that require a more bespoke approach. Recent advances may now mean that even these most recalcitrant of proteins could become tenable structural biology targets on a more routine basis. In this special issue, we examine progress in key areas that suggests this is indeed the case. Our first contribution examines the importance of understanding quality control in the host cell during recombinant protein production, and pays particular attention to the synthesis of recombinant membrane proteins. A major challenge faced by any host cell factory is the balance it must strike between its own requirements for growth and the fact that its cellular machinery has essentially been hijacked by an expression construct. In this context, Bill and von der Haar examine emerging insights into the role of the dependent pathways of translation and protein folding in defining high-yielding recombinant membrane protein production experiments for the common prokaryotic and eukaryotic expression hosts. Rather than acting as isolated entities, many membrane proteins form complexes to carry out their functions. To understand their biological mechanisms, it is essential to study the molecular structure of the intact membrane protein assemblies. Recombinant production of membrane protein complexes is still a formidable, at times insurmountable, challenge. In these cases, extraction from natural sources is the only option to prepare samples for structural and functional studies. Zorman and co-workers, in our second contribution, provide an overview of recent advances in the production of multi-subunit membrane protein complexes and highlight recent achievements in membrane protein structural research brought about by state-of-the-art near-atomic resolution cryo-electron microscopy techniques. E. coli has been the dominant host cell for recombinant protein production. Nonetheless, eukaryotic expression systems, including yeasts, insect cells and mammalian cells, are increasingly gaining prominence in the field. The yeast species Pichia pastoris, is a well-established recombinant expression system for a number of applications, including the production of a range of different membrane proteins. Byrne reviews high-resolution structures that have been determined using this methylotroph as an expression host. Although it is not yet clear why P. pastoris is suited to producing such a wide range of membrane proteins, its ease of use and the availability of diverse tools that can be readily implemented in standard bioscience laboratories mean that it is likely to become an increasingly popular option in structural biology pipelines. The contribution by Columbus concludes the membrane protein section of this volume. In her overview of post-expression strategies, Columbus surveys the four most common biochemical approaches for the structural investigation of membrane proteins. Limited proteolysis has successfully aided structure determination of membrane proteins in many cases. Deglycosylation of membrane proteins following production and purification analysis has also facilitated membrane protein structure analysis. Moreover, chemical modifications, such as lysine methylation and cysteine alkylation, have proven their worth to facilitate crystallization of membrane proteins, as well as NMR investigations of membrane protein conformational sampling. Together these approaches have greatly facilitated the structure determination of more than 40 membrane proteins to date. It may be an advantage to produce a target protein in mammalian cells, especially if authentic post-translational modifications such as glycosylation are required for proper activity. Chinese Hamster Ovary (CHO) cells and Human Embryonic Kidney (HEK) 293 cell lines have emerged as excellent hosts for heterologous production. The generation of stable cell-lines is often an aspiration for synthesizing proteins expressed in mammalian cells, in particular if high volumetric yields are to be achieved. In his report, Buessow surveys recent structures of proteins produced using stable mammalian cells and summarizes both well-established and novel approaches to facilitate stable cell-line generation for structural biology applications. The ambition of many biologists is to observe a protein's structure in the native environment of the cell itself. Until recently, this seemed to be more of a dream than a reality. Advances in nuclear magnetic resonance (NMR) spectroscopy techniques, however, have now made possible the observation of mechanistic events at the molecular level of protein structure. Smith and colleagues, in an exciting contribution, review emerging ‘in-cell NMR’ techniques that demonstrate the potential to monitor biological activities by NMR in real time in native physiological environments. A current drawback of NMR as a structure determination tool derives from size limitations of the molecule under investigation and the structures of large proteins and their complexes are therefore typically intractable by NMR. A solution to this challenge is the use of selective isotope labeling of the target protein, which results in a marked reduction of the complexity of NMR spectra and allows dynamic processes even in very large proteins and even ribosomes to be investigated. Kerfah and co-workers introduce methyl-specific isotopic labeling as a molecular tool-box, and review its applications to the solution NMR analysis of large proteins. Tyagi and Lemke next examine single-molecule FRET and crosslinking following the co-translational incorporation of non-canonical amino acids (ncAAs); the goal here is to move beyond static snap-shots of proteins and their complexes and to observe them as dynamic entities. The encoding of ncAAs through codon-suppression technology allows biomolecules to be investigated with diverse structural biology methods. In their article, Tyagi and Lemke discuss these approaches and speculate on the design of improved host organisms for ‘integrative structural biology research’. Our volume concludes with two contributions that resolve particular bottlenecks in the protein structure determination pipeline. The contribution by Crepin and co-workers introduces the concept of polyproteins in contemporary structural biology. Polyproteins are widespread in nature. They represent long polypeptide chains in which individual smaller proteins with different biological function are covalently linked together. Highly specific proteases then tailor the polyprotein into its constituent proteins. Many viruses use polyproteins as a means of organizing their proteome. The concept of polyproteins has now been exploited successfully to produce hitherto inaccessible recombinant protein complexes. For instance, by means of a self-processing synthetic polyprotein, the influenza polymerase, a high-value drug target that had remained elusive for decades, has been produced, and its high-resolution structure determined. In the contribution by Desmyter and co-workers, a further, often imposing, bottleneck in high-resolution protein structure determination is addressed: The requirement to form stable three-dimensional crystal lattices that diffract incident X-ray radiation to high resolution. Nanobodies have proven to be uniquely useful as crystallization chaperones, to coax challenging targets into suitable crystal lattices. Desmyter and co-workers review the generation of nanobodies by immunization, and highlight the application of this powerful technology to the crystallography of important protein specimens including G protein-coupled receptors (GPCRs). Recombinant protein production has come a long way since Peter Lobban's hypothesis in the late 1960s, with recombinant proteins now a dominant force in structural biology. The contributions in this volume showcase an impressive array of inventive approaches that are being developed and implemented, ever increasing the scope of recombinant technology to facilitate the determination of elusive protein structures. Powerful new methods from synthetic biology are further accelerating progress. Structure determination is now reaching into the living cell with the ultimate goal of observing functional molecular architectures in action in their native physiological environment. We anticipate that even the most challenging protein assemblies will be tackled by recombinant technology in the near future.
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Trade unions in Poland have not built the stable and long-term relations with political parties as are observed in Western democracies. By analysing the historical and symbolic background of the transformation to a democratic civil society and free market economy, political preferences of working class, trade union membership rates, and public opinion polls, we argue that, in case of Poland, the initial links between political parties and trade unions weakened over time. Polish trade unions never had a chance to become a long-term intermediary between society and political parties, making the Polish case study a double exception from the traditional models.
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The paper investigates the relationships between registrations, de-registrations and population density at county level in the UK using VAT data for 20 years over the period 1980–1999. The rationale for this is based on the need to understand how the extent to which, in different parts of the UK, differences in the relationship between birth rates and death rates combine to produce an interpretable pattern in net birth rates. The analysis of the net birth rate shows that a strategy aimed at the net birth rate might, in principle, just as well aim at reducing business failure, rather than raising the birth rate. Indeed this might be more efficient, since it implies that less start-ups are ‘‘wasted’’ as it would avoid the necessity, if targets are to be reached, of encouraging those individuals who are patently unsuited to running their own business into business ownership.
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This research project examined the feasibility of using a cavity transfer mixer (CTM) as a continuous reactor to perform reactions between either solid or liquid reagents and polymer melt; reactions which have previously been typically carried out in batch reactor systems. Equipment has been developed to allow uniform and reproducible introduction of reagents into the polymer melt. Reactions have also been performed using batch processing equipment to enable comparison with the performance of the CTM. It was concluded that: a) there are certain reactions which cannot be carried out in a CTM, but which can be performed in a batch system such as a mill or a sigma blade mixer. This was found to be the case for some neutralisation reactions where the product was quasi crosslinked. b) the reactions that can be carried out in a CTM are performed more efficiently in a CTM than on a batch process. For example, when monomers were to be grafted onto polymers, this was more safely and efficiently performed in the CTM than in a mill or a sigma blade mixer. Residence time distributions (RTDs) for three CTMs were studied in order to gain an insight into the effect of CTM geometry on RTD, polymer melt flow pattern and reactor performance. A mathematical model has been developed to predict the influence of process parameters on RTD and the results compared with experimentally observed trends. The comparison was good. A programme of research has been drawn up to form the basis of an industrially based sponsored development project of the CTM reactor. This work programme was successfully marketed to companies with commercial interest in modified rubber and plastics as an integral part of the research programme of this thesis and the sponsored research programme has paralleled the work reported here.
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The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.
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Purpose – This paper reports the study of key success factors (KSFs) in the project management of the implementation of strategic manufacturing initiatives (SMIs). Design/methodology/approach – In order to gather the experience and knowledge of many industries, from different geographic locations, in a broad range of types and sizes of SMIs, a questionnaire-based survey of practitioners worldwide was selected as the most appropriate research method among those available. Findings – The identification of those tasks and activities that must be done well in order to succeed in the implementation of a SMI in practice. Practical implications – Practitioners focusing their attention on the KSFs identified are more likely to succeed. Once these factors have been identified, the value of benchmarking project management methodologies then comes from drawing attention to those tasks that are key to the success of the implementation of SMIs. Originality/value – The paper presents new thinking by bringing project management into the operations strategy implementation literature as an important mediating factor for success. In this context the factors that are required for successful implementation are identified.
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This paper provides a preliminary comparative longitudinal analysis of the impact on workers made redundant due to the closure of the Mitsubishi plant in Adelaide and the MG Rover plant in Birmingham. Longitudinal surveys of ex-workers from both firms were undertaken over a 12-month period in order to assess the process of labour market adjustment. In the Mitsubishi case, given the skills shortage the state of Adelaide was facing, together with the considerable growth in mining and defence industries, it would have been more appropriate if policy intervention had been redirected to further training or re-skilling opportunities for redundant workers. This opportunity was effectively missed and as a result more workers left the workforce, most notably for retirement, than could have otherwise been the case. The MG Rover case was seen as a more successful example of policy intervention, with greater funding assistance available and targeted support available, and with more emphasis on re-training needs to assist adjustment. However, despite the assistance offered and the rhetoric of successful adjustment in both cases, the majority of workers have nevertheless experienced deterioration in their circumstances particularly in the Australian case where casual and part-time work were often the only work that could be obtained. Even in the UK case, where more funding assistance was offered, a majority of workers reported a decline in earnings and a rise in job insecurity. This suggests that a reliance on the flexible labour market is insufficient to promote adjustment, and that more active policy intervention is needed especially in regard to further up-skilling.
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Objectives. Emotional dysregulation in bipolar disorder is thought to arise from dysfunction within prefrontal cortical regions involved in cognitive control coupled with increased or aberrant activation within regions engaged in emotional processing. The aim of this study was to determine the common and distinct patterns of functional brain abnormalities during reward and working memory processing in patients with bipolar disorder. Methods. Participants were 36 euthymic bipolar disorder patients and 37 healthy comparison subjects matched for age, sex and IQ. Functional magnetic resonance imaging (fMRI) was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task. Results. During both tasks, patients with bipolar disorder demonstrated a pattern of inefficient engagement within the ventral frontopolar prefrontal cortex with evidence of segregation along the medial-lateral dimension for reward and working memory processing, respectively. Moreover, patients also showed greater activation in the anterior cingulate cortex during the Iowa Gambling Task and in the insula during the n-back task. Conclusions. Our data implicate ventral frontopolar dysfunction as a core abnormality underpinning bipolar disorder and confirm that overactivation in regions involved in emotional arousal is present even in tasks that do not typically engage emotional systems. © 2012 Informa Healthcare.
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It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. Word reading and spelling were retested 6 months later, and text reading accuracy and reading comprehension were tested 3 years later. The children with FRD were at increased risk of developing difficulties in reading accuracy, but not reading comprehension. Four groups were compared: good and poor readers with and without FRD. In most cases good readers outperformed poor readers regardless of family history, but there was an effect of family history on naming and nonword repetition regardless of literacy outcome, suggesting a role for speech production skills as an endophenotype of dyslexia. Phonological processing predicted spelling, while language predicted text reading accuracy and comprehension. FRD was a significant additional predictor of reading and spelling after controlling for speech production, language and phonological processing, suggesting that children with FRD show additional difficulties in literacy that cannot be fully explained in terms of their language and phonological skills. It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. © 2014 John Wiley & Sons Ltd.