21 resultados para Post-convertibility accumulation model
em Aston University Research Archive
Resumo:
Background The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors. Results Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism. Conclusion We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.
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Most prior new product diffusion (NPD) models do not specifically consider the role of the business model in the process. However, the context of NPD in today's market has been changed dramatically by the introduction of new business models. Through reinterpretation and extension, this paper empirically examines the feasibility of applying Bass-type NPD models to products that are commercialized by different business models. More specifically, the results and analysis of this study consider the subscription business model for service products, the freemium business model for digital products, and a pre-paid and post-paid business model that is widely used by mobile network providers. The paper offers new insights derived from implementing the models in real-life cases. It also highlights three themes for future research.
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In this paper we present a simple three-sector model explaining the structural change in employment, which is a modified version of Rowthorn-Wells (1987). We supplement the theoretical analysis with simple econometric tests, which illustrate how the modified Rowthorn-Wells model can be used to (i) motivate empirical estimates of the link between the level of development and structures of employment, (ii) illustrate structural distortions under the command economies, and the structural adjustment that happened during the post-Communist transition. We demonstrate that in the case of these economies, the transition process leads to an adjustment to the employment structures predicted by the model.
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1 Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) have structural similarities, interact with each others receptors (calcitonin receptor-like receptor (CLR)/receptor-activity-modifying proteins (RAMPs)) and show overlapping biological activities. AM and CGRP receptors are chiefly coupled to cAMP production. In this study, a method of primary dissociated cell culture was used to investigate the presence of AM and CGRP receptors and their effects on cAMP production in embryonic spinal cord cells. 2 Both neuronal and non-neuronal CLR immunopositive cells were present in our model. 3 High affinity, specific [ 125I]-AM binding sites (K(d) 79±9 pM and B(max) 571±34 fmol mg -1 protein) were more abundant than specific [ 125I]-CGRP binding sites (K(d) 12±0.7 pM and B(max) 32±2 fmol mg -1 protein) in embryonic spinal cord cells. 4 Specific [ 125I]-AM binding was competed by related molecules with a ligand selectivity profile of rAM>hAM(22-52)>rCGRPα>CGRP(8-37) ≫[r-(r*,s*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1, 4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide (BIBN4096BS). 5 Specific [ 125I]-CGRP binding was competed by rCGRPα>rAM≥ CGRP(8-37)≥BIBN4096BS>hAM(22-52). 6 Cellular levels of cAMP were increased by AM (pEC"5"0 10.2±0.2) and less potently by rCGRPα (pEC"5"0 8.9±0.4). rCGRPα-induced cAMP accumulation was effectively inhibited by CGRP(8-37) (pA"2 7.63±0.44) and hAM(22-52) (pA"2 6.18±0.21) while AM-stimulation of cAMP levels was inhibited by CGRP(8-37) (pA"2 7.41±0.15) and AM(22-52) (pA"2 7.26±0.18). BIBN4096BS only antagonized the effects of CGRP (pA"2 8.40±0.30) on cAMP accumulation. 7 These pharmacological profiles suggest that effects of CGRP are mediated by the CGRP"1 (CLR/RAMP1) receptor in our model while those of AM are related to the activation of the AM"1 (CLR/RAMP2) receptor subtype. © 2006 Nature Publishing Group All rights reserved.
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The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.
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How do signals from the 2 eyes combine and interact? Our recent work has challenged earlier schemes in which monocular contrast signals are subject to square-law transduction followed by summation across eyes and binocular gain control. Much more successful was a new 'two-stage' model in which the initial transducer was almost linear and contrast gain control occurred both pre- and post-binocular summation. Here we extend that work by: (i) exploring the two-dimensional stimulus space (defined by left- and right-eye contrasts) more thoroughly, and (ii) performing contrast discrimination and contrast matching tasks for the same stimuli. Twenty-five base-stimuli made from 1 c/deg patches of horizontal grating, were defined by the factorial combination of 5 contrasts for the left eye (0.3-32%) with five contrasts for the right eye (0.3-32%). Other than in contrast, the gratings in the two eyes were identical. In a 2IFC discrimination task, the base-stimuli were masks (pedestals), where the contrast increment was presented to one eye only. In a matching task, the base-stimuli were standards to which observers matched the contrast of either a monocular or binocular test grating. In the model, discrimination depends on the local gradient of the observer's internal contrast-response function, while matching equates the magnitude (rather than gradient) of response to the test and standard. With all model parameters fixed by previous work, the two-stage model successfully predicted both the discrimination and the matching data and was much more successful than linear or quadratic binocular summation models. These results show that performance measures and perception (contrast discrimination and contrast matching) can be understood in the same theoretical framework for binocular contrast vision. © 2007 VSP.
Resumo:
In spite of the increasing significance of broadband, many small and medium enterprises (SMEs) are unaware of or unappreciative of its benefits. This is potentially a problem for governments, Internet Service Providers and other supply side institutions. The current study empirically verifies applicability of an extended IS continuance model controlling for organizational variables based on the Technology-Organization-Environment framework to examine factors influencing broadband post-adoption behavior of SMEs in Singapore. Strong support for the model has been manifested by the results, providing insight into influential factors. Results of the study suggest that perceived usefulness is a strong predictor of users’ continuance intention, followed by satisfaction with broadband usage as a significant but weaker predictor. SMEs in a more competitive business environment and whose key executive possesses greater IT knowledge are more likely to use broadband.
Resumo:
Diabetic nephropathy affects 30-40% of diabetics leading to end-stage kidney failure through progressive scarring and fibrosis. Previous evidence suggests that tissue transglutaminase (tTg) and its protein cross-link product epsilon(gamma-glutamyl)lysine contribute to the expanding renal tubulointerstitial and glomerular basement membranes in this disease. Using an in vitro cell culture model of renal proximal tubular epithelial cells we determined the link between elevated glucose levels with changes in expression and activity of tTg and then, by using a highly specific site directed inhibitor of tTg (1,3-dimethyl-2[(oxopropyl)thio]imidazolium), determined the contribution of tTg to glucose-induced matrix accumulation. Exposure of cells to 36 mm glucose over 96 h caused an mRNA-dependent increase in tTg activity with a 25% increase in extracellular matrix (ECM)-associated tTg and a 150% increase in ECM epsilon(gamma-glutamyl)lysine cross-linking. This was paralleled by an elevation in total deposited ECM resulting from higher levels of deposited collagen and fibronectin. These were associated with raised mRNA for collagens III, IV, and fibronectin. The specific site-directed inhibitor of tTg normalized both tTg activity and ECM-associated epsilon(gamma-glutamyl)lysine. Levels of ECM per cell returned to near control levels with non-transcriptional reductions in deposited collagen and fibronectin. No changes in transforming growth factor beta1 (expression or biological activity) occurred that could account for our observations, whereas incubation of tTg with collagen III indicated that cross-linking could directly increase the rate of collagen fibril/gel formation. We conclude that Tg inhibition reduces glucose-induced deposition of ECM proteins independently of changes in ECM and transforming growth factor beta1 synthesis thus opening up its possible application in the treatment other fibrotic and scarring diseases where tTg has been implicated.
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Since 1979, China has embarked on a series of economic reform programmes, leading its socialist economy away from a Soviet planning model towards a much greater reliance on the market. In the course of the last twenty years, the Chinese economy has enjoyed a phenomenally high economic growth rate. However, earlier research suggests that Chinese state-owned enterprises remain a financial 'black hole' for the Chinese economy, in spite of various enterprise reform measures. This thesis tries to assess the impact of the reforms after 1993, especially the so-called Modern Enterprise System, on the behaviour and management practices of state firms. The central research question is whether the new rounds of economic reform have changed state firms into commercial entities operating according to market signals, as intended. In order to explore this question, an institutional approach is employed. More specifically, the thesis examines how the behaviour and management practices of state enterprises have changed with changes in the institutional environmental resulting from the introduction of new reform measures and especially the MES. The main evidence used in this research comes from the Chinese electronics industry (CEI). Non-state firms, namely collectives and joint ventures, are involved in the study to provide a benchmark against which changes in the behaviour of state firms in the mid and late 1990s are compared. A comparative statistical analysis shows that state-owned firms, both traditional and corporatised ones, still lag behind collectives and joint ventures in terms of both labour and total factor productivity. The further empirical work of this research consists of a questionnaire survey and case studies that are based on interviews with senior managers of 17 firms in the CEI. The findings of these analyses suggest that there has been little fundamental change in the behaviour pattern of state firms in the 1990s, despite the introduction of the Modern Enterprise System, and that the economic reforms after 1993 so far seem to have failed to transform the state firms into commercial entities operating according to market signals.
Resumo:
The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.
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Using panel data for twenty-seven post-communist economies between 1987-2003, we examine the nexus of relationships between inequality, fiscal capacity (defined as the ability to raise taxes efficiently) and the political regime. Investigating the impact of political reform we find that full political freedom is associated with lower levels of income inequality. Under more oligarchic (authoritarian) regimes, the level of inequality is conditioned by the state’s fiscal capacity. Specifically, oligarchic regimes with more developed fiscal systems are able to defend the prevailing vested interests at a lower cost in terms of social injustice. This empirical finding is consistent with the model developed by Acemoglu (2006). We also find that transition countries undertaking early macroeconomic stabilisation now enjoy lower levels of inequality; we confirm that education fosters equality and the suggestion of Commander et al (1999) that larger countries are prone to higher levels of inequality.
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Although event-related potentials (ERPs) are widely used to study sensory, perceptual and cognitive processes, it remains unknown whether they are phase-locked signals superimposed upon the ongoing electroencephalogram (EEG) or result from phase-alignment of the EEG. Previous attempts to discriminate between these hypotheses have been unsuccessful but here a new test is presented based on the prediction that ERPs generated by phase-alignment will be associated with event-related changes in frequency whereas evoked-ERPs will not. Using empirical mode decomposition (EMD), which allows measurement of narrow-band changes in the EEG without predefining frequency bands, evidence was found for transient frequency slowing in recognition memory ERPs but not in simulated data derived from the evoked model. Furthermore, the timing of phase-alignment was frequency dependent with the earliest alignment occurring at high frequencies. Based on these findings, the Firefly model was developed, which proposes that both evoked and induced power changes derive from frequency-dependent phase-alignment of the ongoing EEG. Simulated data derived from the Firefly model provided a close match with empirical data and the model was able to account for i) the shape and timing of ERPs at different scalp sites, ii) the event-related desynchronization in alpha and synchronization in theta, and iii) changes in the power density spectrum from the pre-stimulus baseline to the post-stimulus period. The Firefly Model, therefore, provides not only a unifying account of event-related changes in the EEG but also a possible mechanism for cross-frequency information processing.
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Theoretical and empirical studies show that deindustrialisation, broadly observed in developed countries, is an inherent part of the economic development pattern. However, post-communist countries, while being only middle-income economies, have also experienced deindustrialisation. Building on the model developed by Rowthorn and Wells (1987) we explain this phenomenon and show that there is a strong negative relationship between the magnitude of deindustrialisation and the efficiency and consistency of market reforms. We also demonstrate that reforms of the agricultural sector play a significant role in placing a transition country on a development path that guarantees convergence to EU employment structures.
Resumo:
The aim of this paper is to model the evolution of employment structure in post-communist economies in the broader context of deindustrialisation. The paper builds on the model of structural change developed by Rowthorn and Wells (1987). We show that the starting point of high industry sector share in total employment and its direct fall when productivity of sectors changes in favour of services can be explained in terms of this framework. Moreover, the model can also describe the phenomenon of a further expansion of the agriculture, observed in countries classified as "less consistent" in the reforms implementation. Hence, we distinguish two development paths, the efficient one, called "horizontal", and the inefficient one called "vertical". We illustrate it with empirical data, using alternative measures of structural change and patterns of structural evolutions during transition. Finally, we discuss the link between the EBRD indicators of reforms and structural change. We show that the "quality" of reforms, not the initial GDP level determines a country's development path.
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Many papers claim that a Log Periodic Power Law (LPPL) model fitted to financial market bubbles that precede large market falls or 'crashes', contains parameters that are confined within certain ranges. Further, it is claimed that the underlying model is based on influence percolation and a martingale condition. This paper examines these claims and their validity for capturing large price falls in the Hang Seng stock market index over the period 1970 to 2008. The fitted LPPLs have parameter values within the ranges specified post hoc by Johansen and Sornette (2001) for only seven of these 11 crashes. Interestingly, the LPPL fit could have predicted the substantial fall in the Hang Seng index during the recent global downturn. Overall, the mechanism posited as underlying the LPPL model does not do so, and the data used to support the fit of the LPPL model to bubbles does so only partially. © 2013.