934 resultados para Orthogonal polynomials on the real line
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Purpose – This paper seeks to respond to recent calls for more engagement-based studies of corporate social reporting (CSR) practice by examining the views of corporate managers on the current state of, and future prospects for, social reporting in Bangladesh. Design/methodology/approach – The paper uses a series of interviews with senior managers from 23 Bangladeshi companies representing the multinational, domestic private and public sectors. Findings – Key findings are that the main motivation behind current reporting practice lies in a desire on the part of corporate management to manage powerful stakeholder groups, whilst perceived pressure from external forces, notably parent companies' instructions and demands from international buyers, is driving the process forward. In the latter context it appears that adoption of international social accounting standards and codes is likely to become more prevalent in the future. Reservations are expressed as to whether such a passive compliance strategy is likely to achieve much in the way of real changes in corporate behaviour, particularly when Western developed standards and codes are imposed without consideration of local cultural, economic and social factors. Indeed, such imposition could be regarded as little more than an example of the erection of non-tariff trade barriers rather than representing any meaningful move towards empowering indigenous stakeholder groups. Originality/value – The paper contributes to the literature on CSR in developing countries where there is a distinct lack of engagement-based published studies.
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Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic ß-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5-50 µm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100-1000 µm) increased (1.3-1.5-fold; p
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Interpolated data are an important part of the environmental information exchange as many variables can only be measured at situate discrete sampling locations. Spatial interpolation is a complex operation that has traditionally required expert treatment, making automation a serious challenge. This paper presents a few lessons learnt from INTAMAP, a project that is developing an interoperable web processing service (WPS) for the automatic interpolation of environmental data using advanced geostatistics, adopting a Service Oriented Architecture (SOA). The “rainbow box” approach we followed provides access to the functionality at a whole range of different levels. We show here how the integration of open standards, open source and powerful statistical processing capabilities allows us to automate a complex process while offering users a level of access and control that best suits their requirements. This facilitates benchmarking exercises as well as the regular reporting of environmental information without requiring remote users to have specialized skills in geostatistics.
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The assessment of the reliability of systems which learn from data is a key issue to investigate thoroughly before the actual application of information processing techniques to real-world problems. Over the recent years Gaussian processes and Bayesian neural networks have come to the fore and in this thesis their generalisation capabilities are analysed from theoretical and empirical perspectives. Upper and lower bounds on the learning curve of Gaussian processes are investigated in order to estimate the amount of data required to guarantee a certain level of generalisation performance. In this thesis we analyse the effects on the bounds and the learning curve induced by the smoothness of stochastic processes described by four different covariance functions. We also explain the early, linearly-decreasing behaviour of the curves and we investigate the asymptotic behaviour of the upper bounds. The effect of the noise and the characteristic lengthscale of the stochastic process on the tightness of the bounds are also discussed. The analysis is supported by several numerical simulations. The generalisation error of a Gaussian process is affected by the dimension of the input vector and may be decreased by input-variable reduction techniques. In conventional approaches to Gaussian process regression, the positive definite matrix estimating the distance between input points is often taken diagonal. In this thesis we show that a general distance matrix is able to estimate the effective dimensionality of the regression problem as well as to discover the linear transformation from the manifest variables to the hidden-feature space, with a significant reduction of the input dimension. Numerical simulations confirm the significant superiority of the general distance matrix with respect to the diagonal one.In the thesis we also present an empirical investigation of the generalisation errors of neural networks trained by two Bayesian algorithms, the Markov Chain Monte Carlo method and the evidence framework; the neural networks have been trained on the task of labelling segmented outdoor images.
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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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The irnidazotetrazinones are a novel group of anti tumour agents which have demonstrated good activity against a range of murine tumours and human xenografts. They possess a structure activity relationship similar to the anti tumour triazenes, with the chloroethyl (mitozolomide) and methyl (temozolomide) analogues being active antitumour agents, whilst the ethyl (CCRG 82019) and higher homologues are inactive. This thesiS attempts to elucidate the biological mechanisms responsible for the strict structure-activity relationship observed amongst the imidazotetrazinones. Mitozolomide is the only agent chemically capable of cross-linking DNA , which has been suggested to be responsible fo r the cytotoxicity of this group of agents. Only mitozolomide and ternozolornide Exhibit a marked ditferential toxicity towards the 0 -alkylguanine-DNA alkyltransferase deficient GM892A (Mer-) cell line rather than the proficient Raji cell line (Mer+). The rate of uptake of imidazotetrazinones into cells is similar for all three agents in both cell lines, and does not explain the differing sensitivities to these agents. The effect of drug treatment on the incorporation of precursors into macromolecules, and their pool sizes, was examined. Temozolomide administration was found to alter de novo protein synthesis in both GM892A and Raji cells. Flow cytometric analysis revealed that temozolomide and CCRG 82019 block cells in late S/G2/M phase of the cell cycle , similar to that observed with mitozolomide. The extent of reaction of all three drugs with isolated macromolecules and cellular macromolecules was determined, and differences found, with cellular repair processes influencing the number of alkyl lesions remaining bound to macromolecules. The specific bases formed in calf thymus DNA after treatment with either temozolornide and CCRG 82019 was measured, and it was found that the types and relative amounts of lesions formed, differed, as well as the total level of alkylation. Whereas DNA extracted from imidazotetrazinone treated cells is not affected in its ability to support RNA polymerase activity, an effect is observed on the ability to extract DNA polymerase from drug treated cells. This may suggest that the alkylated DNA must be in intact chromatin for the lesion to manifest its effects. Temozolomide and methyl methanesulphonate do got appear to act with a synergistic mode of action. The 0 -position of guanine is suspected to be a critical site for the action of these types of drugs.
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The effect of stainless steel, glass, zirconium and titanium enamel surfaces on the thermal and photooxidative toughening mechanism of dehydrated castor oil films deposited on these surfaces was investigated using different analytical and spectroscopic methods. The conjugated and non-conjugated double bonds were identified and quantified using both Raman spectroscopy and 1D and 2D NMR spectroscopy. The disappearance of the double bonds in thermally oxidised oil-on-surface films was shown to be concomitant with the formation of hydroperoxides (determined by iodometric titration). The type of the surface had a major effect on the rate of thermal oxidation of the oil, but all of the surfaces examined had resulted in a significantly higher rate of oxidation compared to that of the neat oil. The highest effect was exhibited by the stainless steel surface followed by zirconium enamel, titanium enamel and glass. The rate of thermal oxidation of the oil-on-steel surface (at 100 °C, based on peroxide values) was more than five times faster than that of oil-on-glass and more than 21 times faster than the neat oil when compared under similar thermal oxidative conditions. The rate of photooxidation at 60 °C of oil-on-steel films was found to be about one and half times faster than their rate of thermal oxidation at the same temperature. Results from absorbance reflectance infrared microscopy with line scans taken across the depth of thermally oxidised oil-on-steel films suggest that the thermal oxidative toughening mechanism of the oil occurs by two different reaction pathways with the film outermost layers, i.e. furthest away from the steel surface, oxidising through a traditional free radical oxidation process involving the formation of various oxygenated products formed from the decomposition of allylic hydroperoxides, whereas, in the deeper layers closer to the steel surface, crosslinking reactions predominate.
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Gram-positive bacterial cell wall components including PGN (peptidoglycan) elicit a potent pro-inflammatory response in diverse cell types, including endothelial cells, by activating TLR2 (Toll-like receptor 2) signalling. The functional integrity of the endothelium is under the influence of a network of gap junction intercellular communication channels composed of Cxs (connexins) that also form hemichannels, signalling conduits that are implicated in ATP release and purinergic signalling. PGN modulates Cx expression in a variety of cell types, yet effects in endothelial cells remain unresolved. Using the endothelial cell line b.End5, a 6 h challenge with PGN induced IL-6 (interleukin 6), TLR2 and Cx43 mRNA expression that was associated with enhanced Cx43 protein expression and gap junction coupling. Cx43 hemichannel activity, measured by ATP release from the cells, was induced following 15 min of exposure to PGN. Inhibition of hemichannel activity with carbenoxolone or apyrase prevented induction of IL-6 and TLR2 mRNA expression by PGN, but had no effect on Cx43 mRNA expression levels. In contrast, knockdown of TLR2 expression had no effect on PGN-induced hemichannel activity, but reduced the level of TLR2 and Cx43 mRNA expression following 6 h of PGN challenge. PGN also acutely induced hemichannel activity in HeLa cells transfected to express Cx43, but had no effect in Cx43-deficient HeLa OHIO cells. All ATP responses were blocked with Cx-specific channel blockers. We conclude that acute Cx43 hemichannel signalling plays a role in the initiation of early innate immune responses in the endothelium.
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This thesis begins with a review of the literature on team-based working in organisations, highlighting the variations in research findings, and the need for greater precision in our measurement of teams. It continues with an illustration of the nature and prevalence of real and pseudo team-based working, by presenting results from a large sample of secondary data from the UK National Health Service. Results demonstrate that ‘real teams’ have an important and significant impact on the reduction of many work-related safety outcomes. Based on both theoretical and methodological limitations of existing approaches, the thesis moves on to provide a clarification and extension of the ‘real team’ construct, demarcating this from other (pseudo-like) team typologies on a sliding scale, rather than a simple dichotomy. A conceptual model for defining real teams is presented, providing a theoretical basis for the development of a scale on which teams can be measured for varying extents of ‘realness’. A new twelve-item scale is developed and tested with three samples of data comprising 53 undergraduate teams, 52 postgraduate teams, and 63 public sector teams from a large UK organisation. Evidence for the content, construct and criterion-related validity of the real team scale is examined over seven separate validation studies. Theoretical, methodological and practical implications of the real team scale are then discussed.
On the numerical solution of a Cauchy problem in an elastostatic half-plane with a bounded inclusion
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We propose an iterative procedure for the inverse problem of determining the displacement vector on the boundary of a bounded planar inclusion given the displacement and stress fields on an infinite (planar) line-segment. At each iteration step mixed boundary value problems in an elastostatic half-plane containing the bounded inclusion are solved. For efficient numerical implementation of the procedure these mixed problems are reduced to integral equations over the bounded inclusion. Well-posedness and numerical solution of these boundary integral equations are presented, and a proof of convergence of the procedure for the inverse problem to the original solution is given. Numerical investigations are presented both for the direct and inverse problems, and these results show in particular that the displacement vector on the boundary of the inclusion can be found in an accurate and stable way with small computational cost.
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EEG Hyperscanning is a method for studying two or more individuals simultaneously with the objective of elucidating how co-variations in their neural activity (i.e., hyperconnectivity) are influenced by their behavioral and social interactions. The aim of this study was to compare the performance of different hyper-connectivity measures using (i) simulated data, where the degree of coupling could be systematically manipulated, and (ii) individually recorded human EEG combined into pseudo-pairs of participants where no hyper-connections could exist. With simulated data we found that each of the most widely used measures of hyperconnectivity were biased and detected hyper-connections where none existed. With pseudo-pairs of human data we found spurious hyper-connections that arose because there were genuine similarities between the EEG recorded from different people independently but under the same experimental conditions. Specifically, there were systematic differences between experimental conditions in terms of the rhythmicity of the EEG that were common across participants. As any imbalance between experimental conditions in terms of stimulus presentation or movement may affect the rhythmicity of the EEG, this problem could apply in many hyperscanning contexts. Furthermore, as these spurious hyper-connections reflected real similarities between the EEGs, they were not Type-1 errors that could be overcome by some appropriate statistical control. However, some measures that have not previously been used in hyperconnectivity studies, notably the circular correlation co-efficient (CCorr), were less susceptible to detecting spurious hyper-connections of this type. The reason for this advantage in performance is discussed and the use of the CCorr as an alternative measure of hyperconnectivity is advocated. © 2013 Burgess.
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In the current global economic climate, international HRM is facing unprecedented pressure to become more innovative, effective and efficient. New discourses are emerging around the application of information technology, with 'e-HR' (electronic-enablement of Human Resources), self-service portals and promises of improved services couched as various HR 'value propositions'. This study explores these issues through our engagement with the emergent stream of 'critical' HRM, the broader study of organizational discourse and ethical management theories. We have found that while there is growing research into the take-up of e-HR applications, there is a dearth of investigation into the impact of e-HR on the people involved; in particular, the (re)structuring of social relations between HR functions and line managers in the move away from face-to-face HR support services, to more technology-mediated 'self-service' relationships. We undertake a close reading of personal narratives from a multinational organization, deploying a critical discourse lens to examine different dimensions of e-HR and raise questions about the strong technocratic framing of the international language of people management, shaping line manager enactment of e-HR duties. We argue for a more reflexive stance in the conceptualization e-HR, and conclude with a discussion about the theoretical and practical implications of our study, limitations and suggestions for future research. © 2014 © 2014 Taylor & Francis.
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We examine the impact of the fiber type and dispersion management on the performance of a 16 × 40 Gb/s dense wavelength-division-multiplexing nonreturn-to-zero transmission system. The transmission line is composed of G.652 or G.655 fiber with periodic dispersion compensation and hybrid Raman erbium-doped fiber amplifier amplification.
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A series of propylsulfonic (MCM-SOH) and octyl co-functionalised propylsulfonic (MCM-Oc-SOH) catalysts have been prepared by post modification of MCM-41 with mercaptopropyltrimethoxysilane (MPTS) to achieve SOH surface coverages spanning the range 0.12-1 monolayer. Within the MCM-Oc-SOH series, samples with submonolayer MPTS coverages were further grafted with octyltrimethoxysilane to cap bare hydroxyl sites and tune the hydrophobicity of the support. For the MCM-SO H series NH calorimetry revealed acid strength increases as a function of sulfonic acid loading, with -ΔH(NH ) increasing from 87 to 118 kJ mol. In contrast, MCM-Oc-SOH exhibits a dramatic enhancement of acid strength for submonolayer SOH coverages, with -ΔH(NH ) found to increase to 103 kJ mol. In line with these acid strength measurements the per-site activity of the MCM-SOH series in the esterification of butanol with acetic acid was found to increase with SOH content. Incorporation of octyl groups further promotes esterification activity of all the samples within the MCM-Oc-SOH series, such that the turn over frequency of the sample with the lowest loading of SOH more than doubles. Molecular dynamic simulations indicate that the interaction of isolated sulfonic acid groups with the pore walls is the primary cause of the decrease in acid strength and activity of submonolayer samples within the MCM-SOH series. Incorporation of octyl groups results in a combination of increased hydrophobicity and lateral interactions between adjacent sulfonic acid head groups, resulting in a striking enhancement of acid strength and esterification activity. © 2010 The Royal Society of Chemistry.