Scaling up

Abstract: This article examines the questions of sustaining and extending theory-based educational change, reforms, which are designed laboratories outside of schools and whose motivating theoretical base assumes change elemental aspects of classroom practice. This article defines sustainability of theory-based reform as more than maintaining current implementation, but rather as deepening reforms in ways that allow for flexible response to changes in student, curricular, and school contexts. It draws upon five years of research in schools and classrooms engaged in one of three theory-based reform to discuss five essential factors affecting sustainability: resources, reformers’ learning, knowledge of the first principles of the reform and the support of a community of practice, the principal, and the district. This article then turns to “scaling up.” Rather than merely replicating structures, extending theory-based reform to new sites requires building compatibility between the normative base of the reform with that in the classrooms, schools and districts in which they are growing as well as the capacity of the classroom, school, and district to see it through. This article suggests three main factors that reform founders must focus upon to scale up their reforms—attention to site selection, a proactive stance toward district contexts, and planned transfer of authority. The article concludes that issues of invention, implementation, sustainability, and scale occur simultaneously when going deeper and broader with theory-based change.

1 Effective January 2007, the Discussion Paper series within each division and the Director General's Office of IFPRI were merged into one IFPRI-wide Discussion Paper series. The new series begins with number 00689, reflecting the prior publication of 688 discussion papers within the dispersed series. The earlier series are available on IFPRI's website at Abstract iv

This review is designed to be a comprehensive source for polymer nanocomposite research, including fundamental structure/property relationships, manufacturing techniques, and applications of polymer nanocomposite materials. In addition to presenting the scientific framework for the advances in polymer nanocomposite research, this review focuses on the scientific principles and mechanisms in relation to the methods of processing and manufacturing with a discussion on commercial applications and health/safety concerns (a critical issue for production and scale-up). Hence, this review offers a comprehensive discussion on technology, modeling, characterization, processing, manufacturing, applications, and health/safety concerns for polymer nanocomposites.

Wheat straw is an abundant agricultural residue with low commercial value. An attractive alternative is utilization of wheat straw for bioethanol production. However, production costs based on the current technology are still too high, preventing commercialization of the process. In recent years, progress has been made in developing more effective pretreatment and hydrolysis processes leading to higher yield of sugars. The focus of this paper is to review the most recent advances in pretreatment, hydrolysis and fermentation of wheat straw. Based on the type of pretreatment method applied, a sugar yield of 74-99.6% of maximum theoretical was achieved after enzymatic hydrolysis of wheat straw. Various bacteria, yeasts and fungi have been investigated with the ethanol yield ranging from 65% to 99% of theoretical value. So far, the best results with respect to ethanol yield, final ethanol concentration and productivity were obtained with the native non-adapted Saccharomyses cerevisiae. Some recombinant bacteria and yeasts have shown promising results and are being considered for commercial scale-up. Wheat straw biorefinery could be the near-term solution for clean, efficient and economically-feasible production of bioethanol as well as high value-added products.

Capacitive deionization (CDI) has attracted the interest of the community investigating water treatment technologies since the mid-1960s. The technology is based on the recognition that high-surface-area electrodes, when electrically charged, can quantitatively adsorb ionic components from water, thereby resulting in desalination. The article reviews the theoretical and technological background of CDI, the history of its development, and past and present attempts towards scaling up and commercialization. It also provides a critical review of the advantages and limitations of the technology. In addition, further research approaches necessary to render CDI a mature and competitive technology for the treatment of brackish and surface waters are outlined.

The microbial process of converting organic matter into methane and carbon dioxide is so complex that anaerobic digesters have long been treated as "black boxes." Research into this process during the past few decades has gradually unraveled this complexity, but many questions remain. The major biochemical reactions for forming methane by methanogens are largely understood, and evolutionary studies indicate that these microbes are as different from bacteria as they are from plants and animals. In anaerobic digesters, methanogens are at the terminus of a metabolic web, in which the reactions of myriads of other microbes produce a very limited range of compounds--mainly acetate, hydrogen, and formate--on which the methanogens grow and from which they form methane. "Interspecies hydrogen-transfer" and "interspecies formate-transfer" are major mechanisms by which methanogens obtain their substrates and by which volatile fatty acids are degraded. Our understanding of these reactions and other complex interactions among the bacteria involved in anaerobic digestion is only now to the point where anaerobic digesters need no longer be treated as black boxes.

In aerobic bioprocesses, oxygen is a key substrate; due to its low solubility in broths (aqueous solutions), a continuous supply is needed. The oxygen transfer rate (OTR) must be known, and if possible predicted to achieve an optimum design operation and scale-up of bioreactors. Many studies have been conducted to enhance the efficiency of oxygen transfer. The dissolved oxygen concentration in a suspension of aerobic microorganisms depends on the rate of oxygen transfer from the gas phase to the liquid, on the rate at which oxygen is transported into the cells (where it is consumed), and on the oxygen uptake rate (OUR) by the microorganism for growth, maintenance and production. The gas-liquid mass transfer in a bioprocess is strongly influenced by the hydrodynamic conditions in the bioreactors. These conditions are known to be a function of energy dissipation that depends on the operational conditions, the physicochemical properties of the culture, the geometrical parameters of the bioreactor and also on the presence of oxygen consuming cells. Stirred tank and bubble column (of various types) bioreactors are widely used in a large variety of bioprocesses (such as aerobic fermentation and biological wastewater treatments, among others). Stirred tanks bioreactors provide high values of mass and heat transfer rates and excellent mixing. In these systems, a high number of variables affect the mass transfer and mixing, but the most important among them are stirrer speed, type and number of stirrers and gas flow rate used. In bubble columns and airlifts, the lowshear environment compared to the stirred tanks has enabled successful cultivation of shear sensitive and filamentous cells. Oxygen transfer is often the rate-limiting step in the aerobic bioprocess due to the low solubility of oxygen in the medium. The correct measurement and/or prediction of the volumetric mass transfer coefficient, (k L a), is a crucial step in the design, operation and scale-up of bioreactors. The present work is aimed at the reviewing of the oxygen transfer rate (OTR) in bioprocesses to provide a better knowledge about the selection, design, scale-up and development of bioreactors. First, the most used measuring methods are revised; then the main empirical equations, including those using dimensionless numbers, are considered. The possible increasing on OTR due to the oxygen consumption by the cells is taken into account through the use of the biological enhancement factor. Theoretical predictions of both the volumetric mass transfer coefficient and the enhancement factor that have been recently proposed are described; finally, different criteria for bioreactor scale-up are considered in the light of the influence of OTR and OUR affecting the dissolved oxygen concentration in real bioprocess.

Solid-state fermentation has emerged as a potential technology for the production of microbial products such as feed, fuel, food, industrial chemicals and pharmaceutical products. Its application in bioprocesses such as bioleaching, biobeneficiation, bioremediation, biopulping, etc. has offered several advantages. Utilisation of agro-industrial residues as substrates in SSF processes provides an alternative avenue and value-addition to these otherwise under-or non-utilised residues. Today with better understanding of biochemical engineering aspects, particularly on mathematical modelling and design of bioreactors (fermenters), it is possible to scale up SSF processes and some designs have been developed for commercialisation. It is hoped that with continuity in current trends, SSF technology would be well developed at par with submerged fermentation technology in times to come.

Nitrogenase a b s t r a c t Biological hydrogen production processes offer a technique through which renewable energy sources like biomass can be utilized for the generation of the cleanest energy carrier for the use of mankind. Hydrogen intensive research work has already been carried out on the advancement of these processes, such as the development of genetically modified microorganism, metabolic engineering, improvement of the reactor designs, use of different solid matrices for the immobilization of whole cells, biochemical assisted bioreactor, development of two-stage processes, etc. for higher H 2 -production rates. Maximum H 2 yield is found to be 7.1 mol H 2 /mol glucose. However, major bottlenecks for the commercialization of these processes are lower H 2 yield and rate of H 2 production. Suitable microbial cultures are required to handle waste materials efficiently, which are usually complex in nature. This will serve dual purposes: clean energy generation and bioremediation. Scale-up studies on fermentative H 2 -production processes have been done successfully. Pilot plant trials of the photo-fermentation processes require more attention.

Scaling up of suspension dosage form is considered a challenge as pharmaceutical suspensions are thermodynamically unstable. During the scale-up process, the effect of operational variables on the dispersion process, and physical properties affecting overall attributes need systematic evaluation. Though the scale up process can be studied using dimensional analysis, mathematical modeling, and computer simulation, most of the work in the field of suspension manufacturing still depends on empirical studies and the principles of geometric similarities. Various aspects of the scale up process, technology transfer, and process analytical technology (PAT) applications in suspension manufacturing are discussed.

Temporary immersion systems for plant micropropagation have been described and grouped into 4 categories according to operation: tilting and rocker machines; complete immersion of plant material and renewal of the nutrient medium; partial immersion and a liquid nutrient renewal mechanism; complete immersion by pneumatic driven transfer of liquid medium and without nutrient medium renewal. The positive effects of temporary immersion on micropropagation are indicated for shoot proliferation and microcuttings, microtuberization and somatic embryogenesis. Immersion time, i.e. duration or frequency, is the most decisive parameter for system efficiency.

In the face of an estimated one billion people living in inadequate housing conditions in developing countries the need for scaling up housing supply has become an urgent focus of policy debate. To this end the expansion of the role of the private markets has formed the central thesis of the ‘enabling strategy’ for developing the housing sector as a whole rather than relying on project based approaches such as sites and services and settlement upgrading programmes. Policy recommendations emanating from such a standpoint concentrate on adjustments to supply and demand through deregulation and institutional development of the land and housing markets in developing countries in order to overcome largely external constraints to a more efficient market mechanism. This conception of the enabling strategy, however, has been subject to much debate and criticism for its over-concentration on the private markets and exclusion of alternative/complementary modes of housing provision from seriou...

Microbial alkaline proteases dominate the worldwide enzyme market, accounting for a two-thirds share of the detergent industry. Although protease production is an inherent property of all organisms, only those microbes that produce a substantial amount of extracellular protease have been exploited commercially. Of these, strains of Bacillus sp. dominate the industrial sector. To develop an efficient enzyme-based process for the industry, prior knowledge of various fermentation parameters, purification strategies and properties of the biocatalyst is of utmost importance. Besides these, the method of measurement of proteolytic potential, the selection of the substrate and the assay protocol depends upon the ultimate industrial application. A large array of assay protocols are available in the literature; however, with the predominance of molecular approaches for the generation of better biocatalysts, the search for newer substrates and assay protocols that can be conducted at micro/nano-scale are becoming important. Fermentation of proteases is regulated by varying the C/N ratio and can be scaled-up using fed-batch, continuous or chemostat approaches by prolonging the stationary phase of the culture. The conventional purification strategy employed, involving e.g., concentration, chromatographic steps, or aqueous two-phase systems, depends on the properties of the protease in question. Alkaline proteases useful for detergent applications are mostly active in the pH range 8-12 and at temperatures between 50 and 70C, with a few exceptions of extreme pH optima up to pH 13 and activity at temperatures up to 80-90C. Alkaline proteases mostly have their isoelectric points near to their pH optimum in the range of 8-11. Several industrially important proteases have been subjected to crystallization to extensively study their molecular homology and threedimensional structures.

Over the past half-century, agricultural production gains have provided a platform for rural and urban economic growth worldwide. In African countries, however, agriculture has been widely assumed to have performed badly. Foresight commissioned analyses of 40 projects and programmes in 20 countries where sustainable intensification has been developed during the 1990s-2000s. The cases included crop improvements, agroforestry and soil conservation, conservation agriculture, integrated pest management, horticulture, livestock and fodder crops, aquaculture and novel policies and partnerships. By early 2010, these projects had documented benefits for 10.39 million farmers and their families and improvements on approximately 12.75 million ha. Food outputs by sustainable intensification have been multiplicative -by which yields per hectare have increased by combining the use of new and improved varieties and new agronomic-agroecological management (crop yields rose on average by 2.13-fold), and additive -by which diversification has resulted in the emergence of a range of new crops, livestock or fish that added to the existing staples or vegetables already being cultivated. The challenge is now to spread effective processes and lessons to many more millions of generally small farmers and pastoralists across the whole continent. These projects had seven common lessons for scaling up and spreading: (i) science and farmer inputs into technologies and practices that combine crops-animals with agroecological and agronomic management; (ii) creation of novel social infrastructure that builds trust among individuals and agencies; (iii) improvement of farmer knowledge and capacity through the use of farmer field schools and modern information and communication technologies; (iv) engagement with the private sector for supply of goods and services; (v) a focus on women's educational, microfinance and agricultural technology needs; (vi) ensuring the availability of microfinance and rural banking; and (vii) ensuring public sector support for agriculture. This research forms part of the UK Government's Foresight Global Food and Farming project.

Data mining systems aim to discover patterns and extract useful information from facts recorded in databases. A widely adopted approach to this objective is to apply various machine learning algorithms to compute descriptive models of the available data. Here, we explore one of the main challenges in this research area, the development of techniques that scale up to large and possibly physically distributed databases.

Wet agglomeration processes have traditionally been considered an empirical art, with great difficulties in predicting and explaining observed behaviour. Industry has faced a range of problems including large recycle ratios, poor product quality control, surging and even the total failure of scale up from laboratory to full scale production. However, in recent years there has been a rapid advancement in our understanding of the fundamental processes that control granulation behaviour and product properties. This review critically evaluates the current understanding of the three key areas of wet granulation processes: wetting and nucleation, consolidation and growth, and breakage and attrition. Particular emphasis is placed on the fact that there now exist theoretical models which predict or explain the majority of experimentally observed behaviour. Provided that the correct material properties and operating parameters are known, it is now possible to make useful predictions about how a material will granulate. The challenge that now faces us is to transfer these theoretical developments into industrial practice. Standard, reliable methods need to be developed to measure the formulation properties that control granulation behaviour, such as contact angle and dynamic yield strength. There also needs to be a better understanding of the flow patterns, mixing behaviour and impact velocities in different types of granulation equipment. q S.M. Iveson . ( ) S.M. IÕeson et al.r Powder Technology 117 2001 3-39 6

Significant lessons can be drawn from grassroots experiences of coping with extreme weather for reducing the vulnerability of the urban poor to climate change. This paper examines the household and community coping strategies used by low-income households living in Korail, the largest informal settlement in Dhaka. This includes how they use physical, economic and social means to reduce risk, reduce losses and facilitate recovery from flooding and high temperatures, and shows how grassroots adaptation differs according to the level of risk from flooding. The paper also discusses how local planning and governance mechanisms aimed at adaptation can support these coping strategies, including mainstreaming them into adaptation plans that can be scaled up to the citywide level.

In the smart grid operation and management, reliable and real-time information and communication networks play a very critical role. By integrating the appropriate information and communication technologies (ICT) infrastructure, automated control, sensing and metering technologies, and energy management techniques, the smart grid has emerged as a solution that empowers utilities and consumers to share the responsibilities of operating and managing the power grid more efficiently. This paper presents a survey on the role of ICT in the Smart Grid and Micro grid evolution from conceptual models to implementations.

Alternative vehicles powered by electricity or hydrogen hold the potential to solve a number of challenges that relate to automobile use, such as climate change, deterioration of local air quality, security of energy supply, and high fuel prices. This article addresses the question as to how a transition to vehicles powered by hydrogen or electricity could take place. Recognizing that transitions result from joint development of technology and society, a co-evolutionary, multi-level perspective is adopted. The perspective is used to analyze the dynamics of the relationship between car manufacturers and consumers and developments that put pressure on this relationship. Building on the analysis, two sets of scenarios for a transition to batteryelectric and fuel cell vehicles are identified. In one set of scenarios, tightening emissions regulation stimulates carmakers to scale up experiments with alternative vehicles, moving them into the commercialization phase. In the other set, rising fuel prices prompt carmakers to first extend their current product line-up with plug-in versions, and later with battery-electric and fuel cell vehicles. The two scenarios have different implications for the actors involved and for the requisite supporting infrastructure.

White-rot fungi produce various isoforms of extracellular oxidases including laccase, Mn peroxidase and lignin peroxidase (LiP), which are involved in the degradation of lignin in their natural lignocellulosic substrates. This ligninolytic system of white-rot fungi (WRF) is directly involved in the degradation of various xenobiotic compounds and dyes. This review summarizes the state of the art in the research and prospective use of WRF and their enzymes (lignin-modifying enzymes, LME) for the treatment of industrial effluents, particularly dye containing effluents. The textile industry, by far the most avid user of synthetic dyes, is in need of ecoefficient solutions for its colored effluents. The decolorization and detoxification potential of WRF can be harnessed thanks to emerging knowledge of the physiology of these organisms as well as of the biocatalysis and stability characteristics of their enzymes. This knowledge will need to be transformed into reliable and robust waste treatment processes. D

This report provides a summary of the work performed in this 3-year project sponsored by DOE. The overall objective of this project is to identify new, potentially more costeffective surfactant formulations for improved oil recovery (IOR). The general approach is to use an integrated experimental and computational chemistry effort to improve our understanding of the link between surfactant structure and performance, and from this knowledge, develop improved IOR surfactant formulations.

Hydrodynamic cavitation has been increasingly used as a substitute to conventional acoustic (or ultrasonic) cavitation for process intensification owing to its easy and efficient operation. In this paper, we have put forth conceptual design of a new kind of hydrodynamic cavitation reactor that uses a converging-diverging nozzle for generating pressure variation required for driving radial motion of cavitation bubbles. Moreover, the reactor uses externally introduced bubbles of a suitable gas (argon or air) for cavitation nucleation. This design differs from earlier designs used by researchers where an orifice plate is used for creating cavitating flow. The new design offers a good control over two crucial parameters that affect the cavitation intensity produced, viz. rate of nucleation and nature of pressure variation driving bubble motion. Using numerical simulations of bubble dynamics and associated heat and mass transfer, trends in cavitation intensity produced in the reactor are assessed with varying design parameters. The results of simulation show that the externally introduced bubbles undergo transient motion in the flow through the nozzle generating moderate cavitation intensity. On the basis of results of simulation, some recommendations have been made for the effective design and scale up of the new kind of hydrodynamic cavitation reactors using concept introduced in this paper. ᭧

Environmentally friendlier preparations of chemical compounds and organic or inorganic materials are generally accompanied by the concept of saving resources by optimizing reaction conditions and/or introducing new process technologies. The use of ionic liquids and a solvent-free approach are among these technologies, but in terms of the minimisation of energy and optimization of reaction control both microwave and ultrasound irradiation have now proved to be real options. This review starts from the basic considerations on the separate interaction of microwaves and ultrasound with matter and goes on to explore some laboratory and industrial applications of each type of activation. It is also possible to enhance the effects of high frequency electromagnetic fields, typical of microwaves, or the cavitational energy associated with sonochemistry by combining them with other extreme conditions such as plasmas, high pressure and UV. Finally the simultaneous use of microwaves and ultrasound in a single reactor is described. This novel mixing of technologies has been implemented in order to combine the effects of enhanced energy with improved matter transportation.

In a number of recent guidance documents, the FDA has placed more emphasis on the meaningful comparison of dissolution profile data. For example, the FDA scale-up and post-approval changes–modified release (SUPAC–MR) guidance indicates that similar dissolution profiles for approved and modified formulations is acceptable justification for certain levels of change without prior FDA approval or the need to perform bioequivalence studies. As a result, interest among pharmaceutical scientists has focused on the methodology that is available for the comparison of dissolution profile data. The authors review the literature on the methods that are currently available.

Upcycling is the creation or modification of a product from used materials, components and products which is of equal or higher quality or value than the original. Scaling-up upcycling, in theory, contributes ultimately to reducing carbon emissions by extending lifetimes of used materials, components and products, and thereby decreasing embodied energy. This PhD focuses on the emerging household behaviour of upcycling as niche environmentally significant behaviour. It aims to understand the current upcycling behaviour and factors that influence behaviour in order to develop design and policy interventions to influence behaviour in order to upscale upcycling.

Interviews, a short questionnaire study, a survey and use of a ‘semi-Delphi’ method (a questionnaire study followed by a workshop with experts) were employed. The interviews provided insights into current upcycling behaviour (e.g. approaches to and context for upcycling), behavioural factors influencing upcycling, and potential differences arising from demographic characteristics. The short questionnaire study showed that upcycling has potential to create high attachment leading to product longevity. The survey revealed UK-specific key behavioural factors of upcycling (intention, attitude and subjective norm) and the potential target groups for scaling- up (people in art and design aged 30 years or older) based on group differences. Synthesising the data from the interviews and surveys, 15 promising design and policy interventions for upscaling upcycling were formulated. These interventions were subsequently explored and evaluated through the semi-Delphi study. The outcome pinpointed the suitable actor(s) for each intervention and sets of important and feasible interventions for short-term and long-term success in scaling-up.

This research contributes further to knowledge in design for sustainable behaviour by suggesting interventions beyond product and communication design to influence behaviour, and demonstrating novel use of mixed methods consumer research based on a behaviour model and an existing framework for behaviour understanding and intervention. The research also contributes to knowledge in upcycling theory and practice by providing behavioural insights, factors influencing upcycling and promising interventions for upscaling upcycling in the UK. Finally, a contribution was made to consumer behaviour theory by suggesting and testing a new combination model to understand behaviour.

RIS is a New Delhi-based autonomous policy think-tank supported by the Government of India and devoted to trade and development issues. Its work programme focuses on policy research and capacity building on multilateral trade and financial negotiations, regional economic cooperation in Asia, South-South cooperation, new technologies and development, and strategic policy responses of developing countries to globalization, among other issues. The work of RIS is published in the form of research reports, books, discussion papers, policy briefs and journals.

The International Centre for Research in Agroforestry (ICRAF) initiated in 1987 the Southern Africa Regional Agroforestry Programme in partnership with the national research systems in Malawi, Zambia, Zimbabwe and Tanzania to address the problems of low soil fertility and consequent low crop and livestock production, low cash income, and shortages of fuelwood and timber that are common to most rural households in the region. This paper synthesizes agroforestry research and development during the 1990s from a regional perspective and emphasizes scaling-up of promising technologies. The problem of nutrient-depletion can be overcome using nitrogen-fixing and fast growing tree/shrub species, such as Sesbania sesban, Tephrosia vogelii and Gliricidia sepium, as shortduration planted fallows in rotation with crops. Intercropping of food crops with coppicing trees, annual relay intercropping and biomass transfer technologies were found to be appropriate for soil fertility improvement under specific conditions. Tree fodder banks greatly increase fodder production and enrich livestock diets with protein supplements. Rotational woodlots were developed to meet fuelwood and timber demand and reduce pressure on natural woodlands. Research has identified the potential for a number of indigenous fruits in the region to supplement the food needs of rural families, improve their nutritional status and generate cash income. Achieving the ultimate goals of ensuring food security, alleviating poverty and sustaining the environment will require a massive scaling up of adoption of these agroforestry technologies. Key strategies to accomplish this include: increasing the benefits and targeting of agroforestry technologies (for example, through providing substitutes for costly inputs, improving diversification, marketing and processing of agroforestry products, and employing GIS-based targeting techniques) and information-sharing, training and collaborative partnerships in implementation and dissemination of agroforestry options with all major stakeholders (farmers, non-government organizations, extension services, educational institutions, and policy-makers).

Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-ofconcept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful introduction of a dengue vaccine into immunization programs. (B. Guy). efforts are focused on a tetravalent dengue vaccine (TDV) comprising four recombinant, live, attenuated dengue viruses (CYD-1-4) based on the yellow fever 17D vaccine strain (YFV 17D). This technology originated at the US National Institutes of Health and St Louis University and was further developed at Acambis, now part of Sanofi Pasteur . The live-attenuated and chimeric nature of these vaccine viruses necessitated extensive preclinical and clinical characterization, from the early stages of research through to the ongoing phase III clinical program and industrial development, taking into consideration the specific regulations pertaining to genetically modified organisms (GMO). Of note, a chimeric vaccine against Japanese encephalitis virus (JEV), which is similarly based on the YFV17D vaccine, has recently been licensed (IMOJEV TM , Sanofi Pasteur, Lyon France).

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms (like P-gp efflux). These formidable obstacles often impede drug delivery to the brain. As a result several promising molecules (showing a good potential in in vitro evaluation) are lost from the market for a mere consequence of lack of in vivo response probably because the molecule cannot reach the brain in a sufficient concentration. The options to tailor make molecules for brain, though open to the medical chemist, are a costly proposition in terms of money, manpower and time (almost 50 years). The premedial existing approaches for brain delivery like superficial and ventricular application of chemical or the application of chemicals to brain parenchyma are invasive and hence are less patient friendly, more laborious and require skill and could also damage the brain permanently. In view of these considerations novel drug delivery systems such as the nanoparticles are presently being explored for their suitability for targeted brain delivery.

A method is derived for the design of stirred tank reactors for homogeneous reactions. A simple mixing model proposed previously by Curl (4) is used to compute the effects of finite mixing time on complex chemical reactions. It is also shown how the parameters of the model can be obtained by tracer experiments, or estimated theoretically by the assumption of isotropic turbulence. It is shown that in many practical cases the assumption of ideal mixing is a good approximation. However, the effects of imperfect mixing are more likely to be felt in a large reactor than in a pilot plant. Some quantitative examples are discussed. Methods are derived to compute the average outlet concentration for complex systems such as autothermic reactions, polymerization, crystallization, etc.

The goal of this article is to chart and analyse the development and economical performance of fluidized bed combustion (FBC) and its derivates circulating fluidized bed (CFB) and bubbling fluidized bed (BFB). A descriptive overview is given of the technology and the market penetration is discussed. To make further analysis possible a database is constructed. This database comprises technological and economical data on 491 FBC projects. Analysis of these projects shows that the technology variants (CFB and BFB) diffused differently over time. Drivers, which influenced the market diffusion and technological development are market regulation, environmental legislation and RD&D programs. Important drivers for FBC technology are fuel availability, required applications in the market, innovation spill over and competing technologies. In this article technical characteristics are charted, which show improvements in fuel diversification, technical availability, efficiency and emissions. In terms of economical performance the results show a decline in specific investment cost. Finally, the effect of technological learning and experience on the economical performance of FBC technology is analysed using the experience curve method and theory on economies of scale. A problem with applying the experience curve method is that it is not used often for large power plants like FBC plants and with it lacking a methodological standard. A method is therefore suggested. The analyses yielded progress ratios (PR) from 0.42 to 0.93 for different groups of projects (new plant, repower, retrofit, add-on and conversion) and different parts of the capital breakdown (total project price, engineering, procurement and construction price and boiler price). This means that the specific investment prices (in $/kWe) decline with, respectively, 58% and 7% with every doubling of cumulative installed capacity (in MWe). The progress ratio found for new FBC plants lies between 0.90 and 0.93. These values correspond with the average PR of 0.90 found for power plants in the literature. Further results show that economies of scale have a significant influence on the investment price. Scale factors are found in the range of 0.62-0.81 for different groups of projects. According to these scale factors specific investment price decreases, respectively, between 25% and 12% with every doubling of plant capacity (in MWe).