Bioreaction and separation in preparative batch chromatographic columns : the hydrology of lactose to yield glucose,galactose and oligosaccharides

The initial aim of this project was to improve the performance of a chromatographic bioreactor-separator (CBRS). In such a system, a dilute enzyme solution is pumped continuously through a preparative chromatographic column, while pulses of substrate are periodically injected on to the column. Enzymic reaction and separation are therefore performed in a single unit operation. The chromatographic columns used were jacketed glass columns ranging from 1 to 2 metres long with an internal diameter of 1.5 cm. Linking these columns allowed 1, 2, 3 and 4 metre long CBRS systems to be constructed. The hydrolysis of lactose in the presence of β~galactosidase was the reaction of study. From previous work at Aston University, there appeared to be no difficulties in achieving complete lactose hydrolysis in a CBRS. There did, however, appear to be scope for improving the separative performance, so this was adopted as an initial goal. Reducing the particle size of the stationary phase was identified as a way of achieving this improvement. A cation exchange resin was selected which had an average particle size of around half that previously used when studying this reaction. A CBRS system was developed which overcame the operational problems (such as high pressure drop development) associated with use of such a particle size. A significant improvement in separative power was achieved. This was shown by an increase in the number of theoretical plates (N) from about 500 to about 3000 for a 2 metre long CBRS, coupled with higher resolution. A simple experiment with the 1 metre column showed that combined bioreaction and separation was achievable in this system. Having improved the separative performance of the system, the factors affecting enzymic reaction in a CBRS were investigated; including pulse volume and the degree of mixing between enzyme and substrate. The progress of reaction in a CBRS was then studied. This information was related to the interaction of reaction and separation over the reaction zone. The effect of injecting a pulse over a length of time as in CBRS operation was simulated by fed batch experiments. These experiments were performed in parallel with normal batch experiments where the substrate is mixed almost instantly with the enzyme. The batch experiments enabled samples to be taken every minute and revealed that reaction is very rapid. The hydrodynamic characteristics of the two injector configurations used in CBRS construction were studied using Magnetic Resonance Imaging, combined with hydrodynamic calculations. During the optimisation studies, galactooligosaccharides (GOS) were detected as intermediates in the hydrolysis process. GOS are valuable products with potential and existing applications in food manufacture (as nutraceuticals), medicine and drug targeting. The focus of the research was therefore turned to GOS production. A means of controlling reaction to arrest break down of GOS was required. Raising temperature was identified as a possible means of achieving this within a CBRS. Studies were undertaken to optimise the yield of oligosaccharides, culminating in the design, construction and evaluation of a Dithermal Chromatographic Bioreactor-separator.

A post-structural analysis of perceptions and experiences of continuity and change within the UK automotive supplier base

Firms acting as suppliers to the British automotive industry have a long history of so doing, with some evidencing histories that predate even the invention of the motor car. In exploring the challenges faced by the descendants of these firms in the 1990s, a review is undertaken of the bodies of literature surrounding the changes wrought through the increased globalisation of the industry; the impact of new manufacturing technologies and techniques; the rising levels of co-operation between firms; and the growing impact of the automotive 'service sector'. Moreover, an exploration is undertaken of the perceived 'realities' of the automotive industry as constructed through discourse, including the ways in which discourse effects a continual reinterpretation and re-evaluation of the historical evolution of the industry. Attention is focused on the implications of the above for the automotive supply chain, and the means for its rationalisation proposed by the major car manufacturers and their partner-suppliers. Post-structuralist approaches are introduced as part of an attempt to establish and appropriate research methodology that can explore and deconstruct the discourses surrounding 'modernity', 'supply chain rationalisation', 'flexible specialisation' and 'globalisation' within the automotive industry. Analytical research is conducted into the small- to medium-sized business that constitute the majority of the supplier base in the United Kingdom, and the findings of this research are compared with those of a similar study conducted a quarter-century ago. In this way, the relationships of these firms with their customers, suppliers, and peers are investigated, as are their perceptions of a changing marketplace and their reactions to the impact of policies such as the 'supply chain rationalisation' pursued by the major automotive manufacturers. Authoritative discourses of industry form, function, and structure are challenged, with voice being granted to the marginalised: small suppliers, 'service sector' firms, or those only partly involved in the automotive industry.

The synthesis and evaluation of small organic molecules as cholecystokinin antagonists

Cholecystokinin (CCK) is a peptide hormone, present in the alimentary and the CNS. It is the most abundant peptide in the brain. CCK has been implicated in a number of disorders. The link between CCK and anxiety was the basis for this research. A comprehensive discussion on the many types of CCK receptor antagonists is included. For the drug discovery process, a number of synthetic approaches have been investigated and alternative chemical approaches developed. 1,4-Benzodiazepine analogues were prepared, with substitutents In the 1,2 & 3- position of the benzodiazepine scaffold varied, and substituted 3-anilino benzodiazepines exhibited the greatest in vitro activity towards the CCKA receptor subtype. Through extensive screening, pyrazolinone-ureido derivatives were identified, optimised, SAR studied and re-screened. A comprehensive in vivo study on the most active analogue is included, which has a number of common structural features with L-36S, 260 including activity. Pyrazolinone-amide derivatives, bearing the tryptophan moiety were equally active. A number of existing and novel furan- 2(SH)-one building blocks were prepared, from which a selected mini-library of 4- amino-substituted furan-2(SH)-ones were prepared and evaluated. All synthesised compounds were evaluated in a CCK radiolabelled binding assay (CCKA & CCKB), with compounds demonstrating receptor selectivity and lead structures being discovered. The work in this thesis has identified a number of highly active prime structures, from which further investigations are essential in providing more in vitro & in vivo data and the need to prepare more analogues.

Acoustics of small rooms intended for use as studios

The aims of the work reported in this thesis are: (1) To investigate the application of a Wave Analysis Approach in the study of the acoustics of small rooms where the conditions for a Geometrical Statistical Analysis are not valid.

Elasto-plastic impact of fine particles and fragmentation of small agglomerates

Surface deposition of dense aerosol particles is of major concern in the nuclear industry for safety assessment. This study presents theoretical investigations and computer simulations of single gas-born U3O8 particles impacting with the in-reactor surface and the fragmentation of small agglomerates. A theoretical model for elasto-plastic spheres has been developed and used to analyse the force-displacement and force-time relationships. The impulse equations, based on Newton's second law, are applied to govern the tangential bouncing behaviour. The theoretical model is then incorporated into the Distinct Element Method code TRUBAL in order to perform computer simulated tests of particle collisions. A comparison of simulated results with both theoretical predictions and experimental measurements is provided. For oblique impacts, the results in terms of the force-displacement relationship, coefficients of restitution, trajectory of the impacting particle, and distribution of kinetic energy and work done during the process of impact are presented. The effects of Poisson's ratio, friction, plastic deformation and initial particle rotation on the bouncing behaviour are also discussed. In the presence of adhesion an elasto-plastic collision model, which is an extension to the JKR theory, is developed. Based on an energy balance equation the critical sticking velocity is obtained. For oblique collisions computer simulated results are used to establish a set of criteria determining whether or not the particle bounces off the target plate. For impact velocities above the critical sticking value, computer simulated results for the coefficients of restitution and rebound angles of the particle are presented. Computer simulations of fracture/fragmentation resulting from agglomerate-wall impact have also been performed, where two randomly generated agglomerates (one monodisperse, the other polydisperse), each consisting of 50 primary particles are used. The effects of impact angle, local structural arrangements close to the impact point, and plastic deformation at the contacts on agglomerate damage are examined. The simulated results show a significant difference in agglomerate strength between the two assemblies. The computer data also shows that agglomerate damage resulting from an oblique impact is determined by the normal velocity component rather than the impact speed.

Systematic identification of small molecule adjuvants

Introduction: Adjuvants potentiate immune responses, reducing the amount and dosing frequency of antigen required for inducing protective immunity. Adjuvants are of special importance when considering subunit, epitope-based or more unusual vaccine formulations lacking significant innate immunogenicity. While numerous adjuvants are known, only a few are licensed for human use; principally alum, and squalene-based oil-in-water adjuvants. Alum, the most commonly used, is suboptimal. There are many varieties of adjuvant: proteins, oligonucleotides, drug-like small molecules and liposome-based delivery systems with intrinsic adjuvant activity being perhaps the most prominent. Areas covered: This article focuses on small molecules acting as adjuvants, with the author reviewing their current status while highlighting their potential for systematic discovery and rational optimisation. Known small molecule adjuvants (SMAs) can be synthetically complex natural products, small oligonucleotides or drug-like synthetic molecules. The author provides examples of each class, discussing adjuvant mechanisms relevant to SMAs, and exploring the high-throughput discovery of SMAs. Expert opinion: SMAs, particularly synthetic drug-like adjuvants, are amenable to the plethora of drug-discovery techniques able to optimise the properties of biologically active small molecules. These range from laborious synthetic modifications to modern, rational, effort-efficient computational approaches, such as QSAR and structure-based drug design. In principal, any property or characteristic can thus be designed in or out of compounds, allowing us to tailor SMAs to specific biological functions, such as targeting specific cells or pathways, in turn affording the power to tailor SMAs to better address different diseases.

Growth expectations and financial performance of small businesses:evidence from Latvia

By applying regulatory focus theory, this paper investigates the impact of both initial confidence and of exactness of growth expectations on subsequent financial performance of the small firms. Drawing on the unique data set based on the repeated survey design, we make one of the first attempts to explore the complexity of this relationship empirically. Overall the findings suggest that controlling for other relevant factors, including actual growth, the entrepreneurs having higher growth expectations perform significantly better later on in terms of profitability. In addition, education has a strong modifying effect: the impact of high growth expectations on subsequent profit performance is stronger for entrepreneurs with lower level of education.

Growth expectations of business owners:impact of human capital, firm characteristics and environmental transition

This paper presents an empirical study based on a survey of 399 owners of small and medium size companies in Lithuania. Applying bivariate and ordered probit estimators, we investigate why some business owners expect their firms to expand, while others do not. Our main findings provide evidence that SME owner's generic and specific human capital matter. Those with higher education and 'learning by doing' attributes, either through previous job experience or additional entrepreneurial experience, expect their businesses to expand. The expectations of growth are positively related to exporting and non-monotonically to enterprise size. In addition, we analyse the link between the perceptions of constraints to business activities and growth expectations and find that the factors, which are perceived as main business barriers, are not necessary those which are associated with reduced growth expectations. In particular, perceptions of both corruption and of inadequate tax systems seem to affect growth expectations the most.

A survey of UK selection practices across different organization sizes and industry sectors

This paper presents results of a study examining the methods used to select employees in 579 UK organizations representing a range of different organization sizes and industry sectors. Overall, a smaller proportion of organizations in this sample reported using formalized methods (e.g., assessment centres) than informal methods (e.g., unstructured interviews). The curriculum vitae (CVs) was the most commonly used selection method, followed by the traditional triad of application form, interviews, and references. Findings also indicated that the use of different selection methods was similar in both large organizations and small-to-medium-sized enterprises. Differences were found across industry sector with public and voluntary sectors being more likely to use formalized techniques (e.g., application forms rather than CVs and structured rather than unstructured interviews). The results are discussed in relation to their implications, both in terms of practice and future research.

Decision support for lifecycle planning and risk management of small-scale biomass combined heat and power (bCHP) projects in the UK

Biomass is projected to account for approximately half of the new energy production required to achieve the 2020 primary energy target in the UK. Combined heat and power (CHP) bioenergy systems are not only a highly efficient method of energy conversion, at smaller-scales a significant proportion of the heat produced can be effectively utilised for hot water, space heating or industrial heating purposes. However, there are many barriers to project development and this has greatly inhibited deployment in the UK. Project viability is highly subjective to changes in policy, regulation, the finance market and the low cost incumbent; a high carbon centralised energy system. Unidentified or unmitigated barriers occurring during the project lifecycle may not only negatively impact on the project but could ultimately lead to project failure. The research develops a decision support system (DSS) for small-scale (500 kWe to 10 MWe) biomass combustion CHP project development and risk management in the early stages of a potential project’s lifecycle. By supporting developers in the early stages of project development with financial, scheduling and risk management analysis, the research aims to reduce the barriers identified and streamline decision-making. A fuzzy methodology is also applied throughout the developed DSS to support developers in handling the uncertain or approximate information often held at the early stages of the project lifecycle. The DSS is applied to a case study of a recently failed (2011) small-scale biomass CHP project to demonstrate its applicability and benefits. The application highlights that the proposed development within the case study was not viable. Moreover, further analysis of the possible barriers with the DSS confirmed that some possible modifications to be project could have improved this, such as a possible change of feedstock to a waste or residue, addressing the unnecessary land lease cost or by increasing heat utilisation onsite. This analysis is further supported by a practitioner evaluation survey that confirms the research contribution and objectives are achieved.

Settlement policies for small and medium-sized towns in an African context

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Techonology usage in the supply chain:the case of small 3PLs

In today's supply chain management practices, a successful strategy depends increasingly on the performance of third party logistics (3PLs) providers as they play a key integrative role linking the different supply chain elements more effectively. Information and communications technology (ICT) has become an important element of 3PL competitive capability as it enables higher levels of supply chain integration. Recent industry developments have widened the technological gap between large and small 3PLs. This is critical particularly for those markets populated by a large number of small 3PLs such as the Italian logistics industry. The purpose of this paper is to provide an overview of ICT adoption in small logistics service providers. The focus of the study is the Italian 3PL market. The methodology adopted in this paper is based on the action research framework and it is a combination of theoretical analysis and empirical findings (focus groups and surveys). Firstly, a literature review on ICT dissemination in the international and Italian 3PL industry has been carried out. Then, a field survey has been developed preceded by two focus groups. The empirical investigation examined a sample of 153 small Italian 3PLs on the base of a definition and taxonomy proposed by the authors. The results provide a useful technological profile of the surveyed companies, as well as an analysis of the role of ICT in customising services and of the factors influencing ICT adoption. To give a more robust scientific justification of the survey results, it would be useful to carry out an additional large-scale analysis including other countries with a high presence of small logistics service companies. Furthermore, a complementary case-study analysis would be of help in defining the role of specific factors in different types of 3PL. Further investigations in this field are needed to better understand innovation paths, and how ICT can improve the competitive capabilities of 3PLs and of the wider supply chain. Managers of small 3PLs can use the findings to set-up guidelines for improving a company's technology innovation. Technology vendors can use the findings to better market their service/product into the small logistics service provider segment. Despite the fact that much has been written about the dissemination of ICT, there is still a shortage of research in the field of small 3PLs with little empirical investigation into the usage of ICT by small 3PLs. This paper provides a contribution to filling this void and suggests some possible research directions.

A barrier and techno-economic analysis of small-scale bCHP (biomass combined heat and power) schemes in the UK

bCHP (Biomass combined heat and power) systems are highly efficient at smaller-scales when a significant proportion of the heat produced can be effectively utilised for hot water, space heating or industrial heating purposes. However, there are many barriers to project development and this has greatly inhibited deployment in the UK. Project viability is highly subjective to changes in policy, regulation, the finance market and the low cost fossil fuel incumbent. The paper reviews the barriers to small-scale bCHP project development in the UK along with a case study of a failed 1.5MWel bCHP scheme. The paper offers possible explanations for the project's failure and suggests adaptations to improve the project resilience. Analysis of the project's: capital structuring contract length and bankability; feedstock type and price uncertainty, and plant oversizing highlight the negative impact of the existing project barriers on project development. The research paper concludes with a discussion on the effects of these barriers on the case study project and this industry more generally. A greater understanding of the techno-economic effects of some barriers for small-scale bCHP schemes is demonstrated within this paper, along with some methods for improving the attractiveness and resilience of projects of this kind. © 2014 Elsevier Ltd.

Small business performance:business, strategy and owner-manager characteristics

Purpose: This paper aims to contribute to the understanding of the factors that influence small to medium-sized enterprise (SME) performance and particularly, growth. Design/methodology/approach: This paper utilises an original data set of 360 SMEs employing 5-249 people to run logit regression models of employment growth, turnover growth and profitability. The models include characteristics of the businesses, the owner-managers and their strategies. Findings: The results suggest that size and age of enterprise dominate performance and are more important than strategy and the entrepreneurial characteristics of the owner. Having a business plan was also found to be important. Research limitations/implications: The results contribute to the development of theoretical and knowledge bases, as well as offering results that will be of interest to research and policy communities. The results are limited to a single survey, using cross-sectional data. Practical implications: The findings have a bearing on business growth strategy for policy makers. The results suggest that policy measures that promote the take-up of business plans and are targeted at younger, larger-sized businesses may have the greatest impact in terms of helping to facilitate business growth. Originality/value: A novel feature of the models is the incorporation of entrepreneurial traits and whether there were any collaborative joint venture arrangements. © Emerald Group Publishing Limited.