20 resultados para Being towards death

em Aston University Research Archive


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This note explores the regulatory process of UK privatised utilities through the periodic review of prices. It provides a brief history of the privatisation programme in the UK and the theoretical arguments for the price-cap regulation that has been used. It argues that regulatory process appears to involve a covert dialogue and exchange of information between the regulator and regulated and also a second separate review process that consists of an overt dialogue. Using a semiotic analysis the authors suggest that the unfolding of each of these overt reviews follows a very similar pattern that is constantly being re-enacted. It is concluded that further research is required into the relative importance of the two separate review processes in the setting of the price-cap.

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We sought to determine the extent to which colour (and luminance) signals contribute towards the visuomotor localization of targets. To do so we exploited the movement-related illusory displacement a small stationary window undergoes when it has a continuously moving carrier grating behind it. We used drifting (1.0-4.2 Hz) red/green-modulated isoluminant gratings or yellow/black luminance-modulated gratings as carriers, each curtailed in space by a stationary, two-dimensional window. After each trial, the perceived location of the window was recorded with reference to an on-screen ruler (perceptual task) or the on-screen touch of a ballistic pointing movement made without visual feedback (visuomotor task). Our results showed that the perceptual displacement measures were similar for each stimulus type and weakly dependent on stimulus drift rate. However, while the visuomotor displacement measures were similar for each stimulus type at low drift rates (<4 Hz), they were significantly larger for luminance than colour stimuli at high drift rates (>4 Hz). We show that the latter cannot be attributed to differences in perceived speed between stimulus types. We assume, therefore, that our visuomotor localization judgements were more susceptible to the (carrier) motion of luminance patterns than colour patterns. We suggest that, far from being detrimental, this susceptibility may indicate the operation of mechanisms designed to counter the temporal asynchrony between perceptual experiences and the physical changes in the environment that give rise to them. We propose that perceptual localisation is equally supported by both colour and luminance signals but that visuomotor localisation is predominantly supported by luminance signals. We discuss the neural pathways that may be involved with visuomotor localization. © 2007 Springer-Verlag.

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For many decades, the Kingdom of Saudi Arabia has been widely known for being a reliable oil exporter. This fact, however, has not exempted it from facing significant domestic energy challenges. One of the most pressing of these challenges involves bridging the widening electricity supply-demand gap where, currently, the demand is growing at a very fast rate. One crucial means to address this challenge is through delivering power supply projects with maximum efficiency. Project delivery delay, however, is not uncommon in this highly capital-intensive industry, indicating electricity supplies are not coping with the demand increases. To provide a deeper insight into the challenges of project implementation and efficient practice, this research adopts a pragmatic approach by triangulating literature, questionnaires and semi-structured interviews. The research was conducted in the Saudi Arabian power supply industry – Western Operating Area. A total of 105 usable questionnaires were collected, and 28 recorded, semi-structured interviews were conducted, analysed and synthesised to produce a conceptual model of what constitutes the project implementation challenges in the investigated industry. This was achieved by conducting a comprehensive ranking analysis applied to all 58 identified and surveyed factors which, according to project practitioners in the investigated industry, contribute to project delay. 28 of these project delay factors were selected as the "most important" ones. Factor Analysis was employed to structure these 28 most important project delay factors into the following meaningful set of 7 project implementation challenges: Saudi Electricity Company's contractual commitments, Saudi Electricity Company's communication and coordination effectiveness, contractors' project planning and project control effectiveness, consultant-related aspects, manpower challenges and material uncertainties, Saudi Electricity Company's tendering system, and lack of project requirements clarity. The study has implications for industry policy in that it provides a coherent assessment of the key project stakeholders' central problems. From this analysis, pragmatic recommendations are proposed that, if enacted, will minimise the significance of the identified problems on future project outcomes, thus helping to ensure the electricity supply-demand gap is diminished.

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The imidazotetrazinones are clinically active antitumour agents, temozolomide currently proving successful in the treatment of melanomas and gliomas. The exact nature of the biological processes underlying response are as yet unclear.This thesis attempts to identify the cellular targets important to the cytotoxicity of imidazotetrazinones, to elucidate the pathways by which this damage leads to cell death, and to identify mechanisms by which tumour cells may circumvent this action. The levels of the DNA repair enzymes O6-alkylguanine-DNA-alkyltransferase (O6-AGAT) and 3-methyladenine-DNA-glycosylase (3MAG) have been examined in a range of murine and human cell lines with differential sensitivity to temozolomide. All the cell lines were proficient in 3MAG despite there being 40-fold difference in sensitivity to temozolomide. This suggests that while 3-methyladenine is a major product of temozolomide alkylation of DNA it is unlikely to be a cytotoxic lesion. In contrast, there was a 20-fold variation in O6-AGAT levels and the concentration of this repair enzyme correlated with variations in cytotoxicity. Furthermore, depletion of this enzyme in a resistant, O6-AGAT proficient cell line (Raji), by pre-treatment with the free base O6-methylguanine resulted in 54% sensitisation to the effects of temozolomide. These observations have been extended to 3 glioma cell lines; results that support the view that the cytotoxicity of temozolomide is related to alkylation at the O6-position of guanine and that resistance to this drug is determined by efficient repair of this lesion. It is clear, however, the other factors may influence tumour response since temozolomide showed little differential activity towards 3 established solid murine tumours in vivo, despite different tumour O6-AGAT levels. Unlike mitozolomide, temozolomide is incapable of cross-linking DNA and a mechanism by which O6-methylguanine may exert lethality is unclear. The cytotoxicity of the methyl group may be due to its disruption of DNA-protein interactions, or alternatively cell death may not be a direct result of the alkyl group itself, but manifested by DNA single-strand breaks. Enhanced alkaline elution rates were found for the DNA of Raji cells treated with temozolomide following alkyltransferase depletion, suggesting a relationship between O6-methylguanine and the induction single-strand breaks. Such breaks can activate poly(ADP-ribose) synthetase (ADPRT) an enzyme capable of rapid and lethal depletion of cellular NAD levels. However, at concentrations of temozolomlde relevant in vivo little change in adenine nucleotides was detected in cell lines, although this enzyme would appear important in modulating DNA repair since inhibition of ADPRT potentiated temozolomide cytotoxicity in Raji cells but not O6-AGAT deficient GM892A cells. Cell lines have been reported that are O6-AGAT deficient yet resistant to methylating agents. Thus, resistance to temozolomide may arise not only by removal of the methyl group from the O6-position of guanine, but also from another mechanism involving caffeine-sensitive post-replication repair or mismatch repair activity. A modification of the standard Maxam Gilbert sequencing technique was used to determine the sequence specificity of guanine-N7 alkylation. Temozolomide preferentially alkylated runs of guanines with the intensity of reaction increasing with the number of adjacent guanines in the DNA sequence. Comparable results were obtained with a polymerase-stop assay, although neither technique elucidates the sequence specificity of O6-guanine alkylation. The importance of such specificity to cytotoxicity is uncertain, although guanine-rich sequences are common to the promoter regions of oncogenes. Expression of a plasmid reporter gene under the control of the Ha-ras proto~oncogene promoter was inhibited by alkylation with temozolomide when transfected into cancer cell lines, However, this inhibition did not appear to be related to O6~guanine alkylation and therefore would seem unimportant to the chemotherapeutic activity of temozolomide.

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Future optical networks will require the implementation of very high capacity (and therefore spectral efficient) technologies. Multi-carrier systems, such as Orthogonal Frequency Division Multiplexing (OFDM) and Coherent WDM (CoWDM), are promising candidates. In this paper, we present analytical, numerical, and experimental investigations of the impact of the relative phases between optical subcarriers of CoWDM systems, as well as the effect that the number of independently modulated subcarriers can have on the performance. We numerically demonstrate a five-subcarrier and three-subcarrier 10-GBd CoWDM system with direct detected amplitude shift keying (ASK) and differentially/coherently detected (D) phase shift keying (PSK). The simulation results are compared with experimental measurements of a 32-Gbit/s DPSK CoWDM system in two configurations. The first configuration was a practical 3-modulator array where all three subcarriers were independently modulated, the second configuration being a traditional 2-modulator odd/even configuration, where only odd and even subcarriers were independently modulated. Simulation and experimental results both indicate that the independent modulation implementation has a greater dependency on the relative phases between subcarriers, with a stronger penalty for the center subcarrier than the odd/even modulation scheme.

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The aged population have an increased susceptibility to infection, therefore function of the innate immune system may be impaired as we age. Macrophages, and their precursors monocytes, play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Classically-activated ‘M1’ macrophages are pro-inflammatory, which can be induced by encountering pathogenic material or pro-inflammatory mediators. Alternatively activated ‘M2’ macrophages have a largely reparative role, including clearance of apoptotic bodies and debris from tissues. Despite some innate immune receptors being implicated in the clearance of apoptotic cells, the process has been observed to have a dominant anti-inflammatory phenotype with cytokines such as IL-10 and TGF-ß being implicated. The atherosclerotic plaque contains recruited monocytes and macrophages, and is a highly inflammatory environment despite high levels of apoptosis. At these sites, monocytes differentiate into macrophages and gorge on lipoproteins, resulting in formation of ‘foam cells’ which then undergo apoptosis, recruiting further monocytes. This project seeks to understand why, given high levels of apoptosis, the plaque is a pro-inflammatory environment. This phenomenon may be the result of the aged environment or an inability of foam cells to elicit an anti-inflammatory effect in response to dying cells. Here we demonstrate that lipoprotein treatment of macrophages in culture results in reduced capacity to clear apoptotic cells. The capability of lipoprotein treated macrophages to respond to inflammatory stimuli is also shown. Monocyte recruitment to the plaque is currently under study, as is apoptotic cell-mediated immune modulation of human monocyte-derived macrophages.

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The attitudes of 328 British Secondary School children towards computers were examined in a cross-sectional survey. Measures of both general attitudes towards computers and affective reactions towards working with computers were examined in relation to the sex of the subject, courses studied (computer related/noncomputer related) and availability of a home computer. A differential pattern of results was observed. With respect to general attitudes towards computers, main effects were found for all three independent variables indicating that more favourable attitudes increased as a function of being male, doing computer courses and having a home computer. In contrast to this, affective reactions to working with computers was primarily related to doing computer courses, such that those doing computer courses reported more positive and less negative reactions. The practical and theoretical implications of these results are discussed.

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In earlier work we proposed the idea of requirements-aware systems that could introspect about the extent to which their goals were being satisfied at runtime. When combined with requirements monitoring and self adaptive capabilities, requirements awareness should help optimize goal satisfaction even in the presence of changing run-time context. In this paper we describe initial progress towards the realization of requirements-aware systems with REAssuRE. REAssuRE focuses on explicit representation of assumptions made at design time. When such assumptions are shown not to hold, REAssuRE can trigger system adaptations to alternative goal realization strategies.

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The outsourcing industry is now up for a new challenge: to understand how innovation can be realized from outsourcing engagements. While innovation has been explored and prized within businesses for decades, it is a relatively new topic in the context of outsourcing. And, as such, the perceptions regarding what innovation in outsourcing is, what inhibits or enables innovation in outsourcing, and what client firms are willing to do to ensure they benefit from innovation in outsourcing are still being defined. This paper provides insight into some of the critical aspects in innovation in which both client firms and vendors have taken interest in recent years. We go beyond the simplistic approach we have seen in some recent reports that advocates for the development of trust and close relationships between client firms and vendors as the main enablers of innovation in outsourcing. In our view, innovation in outsourcing can be properly understood only when both contractual and relational aspects are examined as well as the nature of the innovation, i.e. incremental or radical, is explored. Further, we posit that the sourcing model applied has also an impact on the ability to innovate. © 2011 Springer-Verlag.

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Drug export from cells is a major factor in the acquisition of cellular resistance to antimicrobial and cancer chemotherapy, and poses a significant threat to future clinical management of disease. Many of the proteins that catalyse drug efflux do so with remarkably low substrate specificity, a phenomenon known as multidrug transport. For these reasons we need a greater understanding of drug recognition and transport in multidrug pumps to inform research that attempts to circumvent their action. Structural and computational studies have been heralded as being great strides towards a full elucidation of multidrug recognition and transport. In this review we summarise these advances and ask how close we are to a molecular understanding of this remarkable phenomenon. © 2013 Elsevier Ltd.

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Although the importance of dataset fitness-for-use evaluation and intercomparison is widely recognised within the GIS community, no practical tools have yet been developed to support such interrogation. GeoViQua aims to develop a GEO label which will visually summarise and allow interrogation of key informational aspects of geospatial datasets upon which users rely when selecting datasets for use. The proposed GEO label will be integrated in the Global Earth Observation System of Systems (GEOSS) and will be used as a value and trust indicator for datasets accessible through the GEO Portal. As envisioned, the GEO label will act as a decision support mechanism for dataset selection and thereby hopefully improve user recognition of the quality of datasets. To date we have conducted 3 user studies to (1) identify the informational aspects of geospatial datasets upon which users rely when assessing dataset quality and trustworthiness, (2) elicit initial user views on a GEO label and its potential role and (3), evaluate prototype label visualisations. Our first study revealed that, when evaluating quality of data, users consider 8 facets: dataset producer information; producer comments on dataset quality; dataset compliance with international standards; community advice; dataset ratings; links to dataset citations; expert value judgements; and quantitative quality information. Our second study confirmed the relevance of these facets in terms of the community-perceived function that a GEO label should fulfil: users and producers of geospatial data supported the concept of a GEO label that provides a drill-down interrogation facility covering all 8 informational aspects. Consequently, we developed three prototype label visualisations and evaluated their comparative effectiveness and user preference via a third user study to arrive at a final graphical GEO label representation. When integrated in the GEOSS, an individual GEO label will be provided for each dataset in the GEOSS clearinghouse (or other data portals and clearinghouses) based on its available quality information. Producer and feedback metadata documents are being used to dynamically assess information availability and generate the GEO labels. The producer metadata document can either be a standard ISO compliant metadata record supplied with the dataset, or an extended version of a GeoViQua-derived metadata record, and is used to assess the availability of a producer profile, producer comments, compliance with standards, citations and quantitative quality information. GeoViQua is also currently developing a feedback server to collect and encode (as metadata records) user and producer feedback on datasets; these metadata records will be used to assess the availability of user comments, ratings, expert reviews and user-supplied citations for a dataset. The GEO label will provide drill-down functionality which will allow a user to navigate to a GEO label page offering detailed quality information for its associated dataset. At this stage, we are developing the GEO label service that will be used to provide GEO labels on demand based on supplied metadata records. In this presentation, we will provide a comprehensive overview of the GEO label development process, with specific emphasis on the GEO label implementation and integration into the GEOSS.

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The firm is becoming more and more inclusive in its conception. And yet, marketing studies point to the same overwhelming conclusion that marketing, marketing departments and marketers are being increasingly 'pushed out' - excluded. We argue that where and when inclusion-exclusion intersect in the practice of strategic marketing is important, not least because their powerful boundary-setting and spanning roles have a determinant effect on the places and spaces, within which marketing strategists are (counter-) mobilized. This paper provides new insights relating to the contradictory forces existing around inclusion-exclusion in corporate strategizing. A further aim is to present the position of marketing (non-) influence within this context. The paper provides a unique theoretical contribution by illustrating some of the contradictions, struggles and activities that make the theoretical shift towards strategic inclusivity unstable, partial and by no means inevitable. A further contribution is a linking of this broader strategic debate, with anxieties over the influence of marketing in corporate strategizing. This leads to a discussion of the various ways that marketing research can sooth the anxiety of influence on multiple fronts via: understanding agency and strategic action; shaping marketing curriculum development; and, reconsidering the spatial dimensions of marketing influence. © 2010 Taylor & Francis.

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The traditional role of ports in the wider supply chain context is currently being subject to a process of radical review. In broad terms, the traditional model is being replaced by a model which focuses on higher value and more knowledge intensive activities. This trend requires a change in the way in which new knowledge and skills are developed by staff in companies of all kinds within port communities. Traditional models need to be re-evaluated to reflect the increasing importance of knowledge and skills acquisition, particularly in relation to the supply chain management (SCM) concept and the evolving role of information and communications technology (ICT) in improving supply chain capability. This paper describes the case of NITL’s Foundation Certificate Programme (FCP) learning programme with specific reference to its use in addressing some of current shortcomings related to supply chain knowledge and skills in port communities. The FCP rationale is based on the need to move from traditional approaches of supply chain organisation where the various links in the chain were measured and managed in isolation from each other and thus tended to operate at cross purposes, towards more cooperative and integrated approaches.

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When people monitor a visual stream of rapidly presented stimuli for two targets (T1 and T2), they often miss T2 if it falls into a time window of about half a second after T1 onset—the attentional blink (AB). We provide an overview of recent neuroscientific studies devoted to analyze the neural processes underlying the AB and their temporal dynamics. The available evidence points to an attentional network involving temporal, right-parietal and frontal cortex, and suggests that the components of this neural network interact by means of synchronization and stimulus-induced desynchronization in the beta frequency range. We set up a neurocognitive scenario describing how the AB might emerge and why it depends on the presence of masks and the other event(s) the targets are embedded in. The scenario supports the idea that the AB arises from ‘‘biased competition’’, with the top–down bias being generated by parietal–frontal interactions and the competition taking place between stimulus codes in temporal cortex.

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This paper considers the religious practices of Tamil Hindus who have settled in the West Midlands and South West of England in order to explore how devotees of a specific ethno-regional Hindu tradition with a well-established UK infrastructure in the site of its adherents’ population density adapt their religious practices in settlement areas which lack this infrastructure. Unlike the majority of the UK Tamil population who live in the London area, the participants in this study did not have ready access to an ethno-religious infrastructure of Tamil-orientated temples and public rituals. The paper examines two means by which this absence was addressed as well as the intersections and negotiations of religion and ethnicity these entailed: firstly, Tamil Hindus’ attendance of temples in their local area which are orientated towards a broadly imagined Hindu constituency or which cater to a non-Tamil ethno-linguistic or sectarian community; and, secondly, through the ‘DIY’ performance of ethnicised Hindu ritual in non-institutional settings.