865 resultados para CASE-II-DIFFUSION
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Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.
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The aim of this work was to elucidate the oxidative folding mechanism of the macrocyclic cystine knot protein MCoTI-II. We aimed to investigate how the six-cysteine residues distributed on the circular backbone of the reduced unfolded peptide recognize their correct partner and join up to form a complex cystine-knotted topology. To answer this question, we studied the oxidative folding of the naturally occurring peptide using a range of spectroscopic methods. For both oxidative folding and reductive unfolding, the same disulfide intermediate species was prevalent and was characterized to be a native-like two-disulfide intermediate in which the Cys(1)-Cys(18) disulfide bond was absent. Overall, the folding pathway of this head-to-tail cyclized protein was found to be similar to that of linear cystine knot proteins from the squash family of trypsin inhibitors. However, the pathway differs in an important way from that of the cyclotide kalata B1, in that the equivalent two-disulfide intermediate in that case is not a direct precursor of the native protein. The size of the embedded ring within the cystine knot motif appears to play a crucial role in the folding pathway. Larger rings contribute to the independence of disulfides and favor an on-pathway native-like intermediate that has a smaller energy barrier to cross to form the native fold. The fact that macrocyclic proteins are readily able to fold to a complex knotted structure in vitro in the absence of chaperones makes them suitable as protein engineering scaffolds that have remarkable stability.
Spectroscopic characterization of copper(II) binding to the immunosuppressive drug mycophenolic acid
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Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric phospholipids. To combat this interaction we have investigated the potential of MPA to coordinate Cu(II), a metal which has been used to inhibit gastropathy associated with use of the NSAID indomethacin. Using a range of spectroscopic techniques we show that Cu(II) is coordinated to two MPA molecules via carboxylates and, at low pH, water ligands. The copper complex formed is stable in solution as assessed by mass spectrometry and H-1 NMR diffusion experiments. Competition studies with glycine and albumin indicate that the copper-MPA complex will release Cu(II) to amino acids and proteins thereby allowing free MPA to be transported to its site of action. Transfer to serum albumin proceeds via a Cu(MPA)(albumin) ternary complex. These results raise the possibility that copper complexes of MPA may be useful in a therapeutic situation.
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Like any other natural resources, hydro resources that are capable of generating electricity at cheaper cost give rise to economic rent. Nepal possesses huge amount of such cheaper hydro resources which is far in excess of the domestic demand. The existing rents levied by the governments are not found to address the potential value of resources. In this study hydro rent is calculated for two types of hydropower projects: (i) domestic demand oriented project and (ii) large and export oriented project. In doing so, the study uses the concept of hydro rent as a measure of cost savings achievable by the use of hydro resources over the least cost alternatives. The WASP-III+ optimisation software developed by IAEA has been used to derive two least cost generation expansion plans i.e. one with and the other without the nominated hydro resource. The difference in the costs of two plans gives the rent of the hydro resource.
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The occurrence of rockbursts was quite common during active mining periods in the Champion reef mines of Kolar gold fields, India. Among the major rockbursts, the ‘area-rockbursts’ were unique both in regard to their spatio-temporal distribution and the extent of damage caused to the mine workings. A detailed study of the spatial clustering of 3 major area-rockbursts (ARB) was carried out using a multi-fractal technique involving generalized correlation integral functions. The spatial distribution analysis of all 3 area-rockbursts showed that they are heterogeneous. The degree of heterogeneity (D2 – D∞) in the cases of ARB-I, II and III were found to be 0.52, 0.37 and 0.41 respectively. These differences in fractal structure indicate that the ARBs of the present study were fully controlled by different heterogeneous stress fields associated with different mining and geological conditions. The present study clearly showed the advantages of the application of multi-fractals to seismic data and to characterise, analyse and examine the area-rockbursts and their causative factors in the Kolar gold mines.
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A inserção de uma igreja evangélica em um assentamento rural do Movimento dos Trabalhadores Rurais Sem-terra (MST), é objeto de nosso estudo de caso neste presente trabalho. A dissertação pesquisa e analisa a inserção dos evangélicos batistas no assentamento Antonio Conselheiro II na região do Pontal do Paranapanema, no estado de São Paulo, assim como a conseqüente implantação neste da Congregação Batista Monte Sião . Partindo de uma perspectiva teórica e empírica, o objetivo concentra-se em analisar a experiência de vida dos assentados batistas no interior do assentamento, buscando retratar as formas, tanto conceptuais como práticas, que estes vivenciam sua fé, costumes e crenças, sonhos e ideais, sempre procurando tecer relações que nos permitam melhor avaliar a forma como os mesmos compreendiam e comunicavam sua fé enquanto assentados do MST. Da apreciação crítica dos relatos obtidos nas entrevistas e dos dados do questionário, ambos aplicados aos agentes de nossa pesquisa, surge uma história que nos desvela faces de uma relação identitária que mescla ideologia e fé, ser evangélico batista e assentado no MST, bem como uma proposição internalizada de uma metodologia da não-violência nas manifestações do movimento Sem-terra.(AU)
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Public policy becomes managerial practice through a process of implementation. There is an established literature within Implementation Studies which explains the variables and some of the processes involved in implementation, but less attention has been focused upon how public service managers convert new policy initiatives into practice. The research proposes that managers and their organisations have to go through a process of learning in order to achieve the implementation of public policy. Data was collected over a five year period from four case studies of capital investment appraisal in the British National Health Service. Further data was collected from taped interviews by key actors within the case studies. The findings suggest that managers do learn to implement policy and four factors are important in this learning process. These are; (i) the nature of bureaucratic responsibility; (ii) the motivation of actors towards learning; (iii) the passage of time which allows for the development of competence and (iv) the use of project team structures. The research has demonstrated that the conversion of policy into practice occurs through the operationalisation of solutions to policy problems via job tasks. As such it suggests that in understanding how policy is implemented, technical learning is more important than cultural learning, in this context. In conclusion, a "Model of Learned Implementation" is presented, together with a discussion of some of the implications of the research. These are the possible use of more pilot projects for new policy initiatives and the more systematic diffusion of knowledge about implementation solutions.
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The aim of this study was to examine the diffusion of commonly administered analgesics, ibuprofen and paracetamol, through gastric mucus. As ibuprofen and paracetamol are often formulated with alkalising excipients, or are commonly co-administered with antacids that have been demonstrated to alter their absorption, diffusion was also studied in the presence of a range of soluble and insoluble antacids or buffering agents. The effect of pH, which has been demonstrated to modify the properties of mucus, was also studied. Mucus was a significant barrier to diffusion for both drugs, compared to an unstirred aqueous layer with diffusion rates significantly lower in the presence of a mucus barrier for both drugs; ibuprofen diffusion also demonstrated a significant increase in the lag time. Paracetamol diffusion was not significantly affected by addition of any antacid, whereas ibuprofen rates were affected and the diffusion lag time for ibuprofen was significantly reduced in all cases. Isolated increases in pH increased the rate and reduced the lag time for ibuprofen diffusion. It was shown that mucus acts as a passive barrier in the case of paracetamol diffusion, and an interactive barrier to ibuprofen diffusion. Changes in mucus viscosity at different pH values may be responsible for the observed changes in ibuprofen diffusion rate. © 2004 Elsevier B.V. All rights reserved.
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Various hypotheses could explain the relationship between beta-amyloid (Abeta) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of Abeta deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Abeta and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (>10 microm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (<10 microm) capillaries. There were no negative correlations between the density of Abeta deposits and the smaller diameter capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessel profiles. In addition, the density of the classic deposits declined as a negative exponential function with distance from a vertically penetrating arteriole. These results suggest that the classic Abeta deposits cluster around the larger blood vessels in the upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.
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In this contribution, certain aspects of the nonlinear dynamics of magnetic field lines are reviewed. First, the basic facts (known from literature) concerning the Hamiltonian structure are briefly summarized. The paper then concentrates on the following subjects: (i) Transition from the continuous description to discrete maps; (ii) Characteristics of incomplete chaos; (iii) Control of chaos. The presentation is concluded by some remarks on the motion of particles in stochastic magnetic fields.
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Considerable attention has been given in the literature to identifying and describing the effective elements which positively affect the improvement of product reliability. These have been perceived by many as the 'state of the art' in the manufacturing industry. The applicability, diffusion and effectiveness of such methods and philosophies, as a means of systematically improving the reliability of a product, come in the main from case studies and single and infra-industry empirical studies. These studies have both been carried out within the wider context of quality assurance and management, and taking reliability as a discipline in its own right. However, it is somewhat of a surprise that there are no recently published findings or research studies on the adoption of these methods by the machine tool industry. This may lead one to construct several hypothesised paradigms: (a) that machine tool manufacturers compared to other industries, are slow to respond to propositions given in the literature by theorists or (b) this may indicate that a large proportion of the manufacturers make little use of the reliability improvement techniques as described in the literature, with the overall perception that they will not lead to any significant improvements? On the other hand, it is evident that hypothetical verification of the operational and engineering methods of reliability achievement and improvement adopted in the machine tool industry is less widely researched. Therefore, research into this area is needed in order to explore the 'state of the art' practice in the machine tool industry. This is in terms of the status, structure and activities of the operation of the reliability function. This paper outlines a research programme being conducted with the co-operation of a leading machine tool manufacturer, whose UK manufacturing plant produces in the main Vertical Machining Centres (VMCs) and is continuously undergoing incremental transitions in product reliability improvement.
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The role of technology management in achieving improved manufacturing performance has been receiving increased attention as enterprises are becoming more exposed to competition from around the world. In the modern market for manufactured goods the demand is now for more product variety, better quality, shorter delivery and greater flexibility, while the financial and environmental cost of resources has become an urgent concern to manufacturing managers. This issue of the International Journal of Technology Management addresses the question of how the diffusion, implementation and management of technology can improve the performance of manufacturing industries. The authors come from a large number of different countries and their contributions cover a wide range of topics within this general theme. Some papers are conceptual, others report on research carried out in a range of different industries including steel production, iron founding, electronics, robotics, machinery, precision engineering, metal working and motor manufacture. In some cases they describe situations in specific countries. Several are based on presentations made at the UK Operations Management Association's Sixth International Conference held at Aston University at which the conference theme was 'Achieving Competitive Edge: Getting Ahead Through Technology and People'. The first two papers deal with questions of advanced manufacturing technology implementation and management. Firstly Beatty describes a three year longitudinal field study carried out in ten Canadian manufacturing companies using CADICAM and CIM systems. Her findings relate to speed of implementation, choice of system type, the role of individuals in implementation, organization and job design. This is followed by a paper by Bessant in which he argues that a more a strategic approach should be taken towards the management of technology in the 1990s and beyond. Also considered in this paper are the capabilities necessary in order to deploy advanced manufacturing technology as a strategic resource and the way such capabilities might be developed within the firm. These two papers, which deal largely with the implementation of hardware, are supplemented by Samson and Sohal's contribution in which they argue that a much wider perspective should be adopted based on a new approach to manufacturing strategy formulation. Technology transfer is the topic of the following two papers. Pohlen again takes the case of advanced manufacturing technology and reports on his research which considers the factors contributing to successful realisation of AMT transfer. The paper by Lee then provides a more detailed account of technology transfer in the foundry industry. Using a case study based on a firm which has implemented a number of transferred innovations a model is illustrated in which the 'performance gap' can be identified and closed. The diffusion of technology is addressed in the next two papers. In the first of these, by Lowe and Sim, the managerial technologies of 'Just in Time' and 'Manufacturing Resource Planning' (or MRP 11) are examined. A study is described from which a number of factors are found to influence the adoption process including, rate of diffusion and size. Dahlin then considers the case of a specific item of hardware technology, the industrial robot. Her paper reviews the history of robot diffusion since the early 1960s and then tries to predict how the industry will develop in the future. The following two papers deal with the future of manufacturing in a more general sense. The future implementation of advanced manufacturing technology is the subject explored by de Haan and Peters who describe the results of their Dutch Delphi forecasting study conducted among a panel of experts including scientists, consultants, users and suppliers of AMT. Busby and Fan then consider a type of organisational model, 'the extended manufacturing enterprise', which would represent a distinct alternative pure market-led and command structures by exploiting the shared knowledge of suppliers and customers. The three country-based papers consider some strategic issues relating manufacturing technology. In a paper based on investigations conducted in China He, Liff and Steward report their findings from strategy analyses carried out in the steel and watch industries with a view to assessing technology needs and organizational change requirements. This is followed by Tang and Nam's paper which examines the case of machinery industry in Korea and its emerging importance as a key sector in the Korean economy. In his paper which focuses on Venezuela, Ernst then considers the particular problem of how this country can address the problem of falling oil revenues. He sees manufacturing as being an important contributor to Venezuela's future economy and proposes a means whereby government and private enterprise can co-operate in development of the manufacturing sector. The last six papers all deal with specific topics relating to the management manufacturing. Firstly Youssef looks at the question of manufacturing flexibility, introducing and testing a conceptual model that relates computer based technologies flexibility. Dangerfield's paper which follows is based on research conducted in the steel industry. He considers the question of scale and proposes a modelling approach determining the plant configuration necessary to meet market demand. Engstrom presents the results of a detailed investigation into the need for reorganising material flow where group assembly of products has been adopted. Sherwood, Guerrier and Dale then report the findings of a study into the effectiveness of Quality Circle implementation. Stillwagon and Burns, consider how manufacturing competitiveness can be improved individual firms by describing how the application of 'human performance engineering' can be used to motivate individual performance as well as to integrate organizational goals. Finally Sohal, Lewis and Samson describe, using a case study example, how just-in-time control can be applied within the context of computer numerically controlled flexible machining lines. The papers in this issue of the International Journal of Technology Management cover a wide range of topics relating to the general question of improving manufacturing performance through the dissemination, implementation and management of technology. Although they differ markedly in content and approach, they have the collective aim addressing the concepts, principles and practices which provide a better understanding the technology of manufacturing and assist in achieving and maintaining a competitive edge.
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Diffusion processes are a family of continuous-time continuous-state stochastic processes that are in general only partially observed. The joint estimation of the forcing parameters and the system noise (volatility) in these dynamical systems is a crucial, but non-trivial task, especially when the system is nonlinear and multimodal. We propose a variational treatment of diffusion processes, which allows us to compute type II maximum likelihood estimates of the parameters by simple gradient techniques and which is computationally less demanding than most MCMC approaches. We also show how a cheap estimate of the posterior over the parameters can be constructed based on the variational free energy.
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The IRDS standard is an international standard produced by the International Organisation for Standardisation (ISO). In this work the process for producing standards in formal standards organisations, for example the ISO, and in more informal bodies, for example the Object Management Group (OMG), is examined. This thesis examines previous models and classifications of standards. The previous models and classifications are then combined to produce a new classification. The IRDS standard is then placed in a class in the new model as a reference anticipatory standard. Anticipatory standards are standards which are developed ahead of the technology in order to attempt to guide the market. The diffusion of the IRDS is traced over a period of eleven years. The economic conditions which affect the diffusion of standards are examined, particularly the economic conditions which prevail in compatibility markets such as the IT and ICT markets. Additionally the consequences of the introduction of gateway or converter devices into a market where a standard has not yet been established is examined. The IRDS standard did not have an installed base and this hindered its diffusion. The thesis concludes that the IRDS standard was overtaken by new developments such as object oriented technologies and middleware. This was partly because of the slow development process of developing standards in traditional organisations which operate on a consensus basis and partly because the IRDS standard did not have an installed base. Also the rise and proliferation of middleware products resulted in exchange mechanisms becoming dominant rather than repository solutions. The research method used in this work is a longitudinal study of the development and diffusion of the ISO/EEC IRDS standard. The research is regarded as a single case study and follows the interpretative epistemological point of view.
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This study aims to explore the position of diffusion oriented support mechanisms in European Community (EC) innovation policy. With the shift from the traditional linear model towards an integrative approach to innovation, the role of diffusion of technologies and knowledge, achieved greater weight. This shift in both the thinking of academic experts, and of national policy makers, induced EC policy makers to appeal for similar changes in Community innovation policy. From the mid-1980s, the Commission of the European Communities, the key actor in EC policy making, thought to move its innovation policy away from the traditional science push approach. This study shows that in the implementation of programmes for research, technology and innovation, the traditional linear model is still dominant. The core research and technological development programmes still operate from a science push concept of innovation, mainly due to their pre-competitive nature. The case of SPRINT illustrates that policy programmes with an integrated innovation perspective can be successful at Community level. However the programme operates in a relatively isolated position from overall research and technological development policy. The case of BRITE-EURAM illustrates the difficulties of collaborative research programmes, the bulk of EC support mechanisms, to move away from the traditional model. The study shows how conflicting policy objectives arising from the different policy networks that shape EC policy making, in combination with a lack of co-ordination in those policy domains, hinder the emergence of the integrated approach. Consequently EC diffusion policy, implemented from the perspective of the linear model, will have a sub-optimal impact on the competitiveness of European industries.