Studies on DNA methylation and mechanisms of hypomethylation

The methylation of cytosinc residues in DNA is thought to play an important role in the regulation of gene expression, with active genes generally being hypomethylated. With this in mind peptides were synthcsised to mimic the cytosine-5 methylation activity carried out by DNA mcthylase, which however, showed no ability to carry out this function. The imidazotetrazinoncs are a novel group of antitumour agents which have demonstrated good activity against a range of murinc tumours and human tumour xenografts, and hypomethylation of DNA has been implicated in the mechanism of action. Studies have been conducted on the mechanism by which such agents cause hypomethylation, using DNA methylase partially purified from murine L1210 leukaemia cells. Unmodified calf thymus DNA does not inhibit the transfer of methyl groups from SAM to M.lysodeikticus DNA by partially purified DNA methylase. However, if the calf thymus DNA is modified by alkylating agents such as imida-zotetrazinones or nitrosoureas, the treated DNA becomes an inhibitor of the methylation reaction. This has been correlated with the induction of DNA damage, such as single strand breaks, since X-ray treated DNA and deoxyribonuclease treatment produces a similar effect. The mechanism of inhibition by the drug treated or damaged DNA is thought to occur by binding of the enzyme to an increased concentration of non-substrate DNA, presumably by the occurrence of single strand breaks, since neither sonication nor treatment with the restriction enzyme Mspl caused an inhibition. Attempts were made to elucidate the strict structure activity relationship for antitumour activity observed amongst the imidazotctrazinones. The transfection of a murine colon adcnocarcinoma cell line (MAC 13) with DNA extracted from GM892 or Raji cells previously treated with either the methyl (temozolomide) or ethyl (ethazolastone) imidazotetrazinone was performed. X-irradiated DNA did not cause any suppression of cell growth, suggesting that it was not due to physical damage. Transfection of MAC 13 cells with DNA extracted from GM892 cells, was more effective at inhibiting growth than DNA from Raji cells. Temozolomide treated cellular DNA was a more potent growth inhibitor than that from ethazolastone treated cells. For both agents the growth inhibitory effect was most marked with DNA extracted 6h after drug addition, and after 24h no growth suppression was observed. This suggested that the growth inhibitory effect is due to a repairable lesion. .The methylation of M.lysodeikticus DNA by DNA methylase is inhibited potently and specifically by both hereto and homoribo and dcoxyri-bopolynucleotides containing guanine residues. The inhibitory effect is unaffected by chain length or sugar residue, but is abolished when the O-6 residue of guanine is substituted as in poly d(OGG)2o. Potent inhibition is also shown by polyinosinic and polyxanthylic acids but not by polyadenylic acid or by heteropolymers containing adcnine and thymine. These results suggest that the 6 position of the purine nucleus is important in binding of the DNA methylase to particular regions of the DNA and that the hydrogen bonding properties of this group are important in enzyme recognition. This was confirmed using synthetic oligonucleotides as substrates for DNA methylase. Enzymatic methylation of cytosine is completely suppressed, when O6 methylguanine replaces guanine in CG sites.

Spatial contrast sensitivity and external noise: applications to optical and neural modulation transfer functions

The thesis will show how to equalise the effect of quantal noise across spatial frequencies by keeping the retinal flux (If-2) constant. In addition, quantal noise is used to study the effect of grating area and spatial frequency on contrast sensitivity resulting in the extension of the new contrast detection model describing the human contrast detection system as a simple image processor. According to the model the human contrast detection system comprises low-pass filtering due to ocular optics, addition of light dependent noise at the event of quantal absorption, high-pass filtering due to the neural visual pathways, addition of internal neural noise, after which detection takes place by a local matched filter, whose sampling efficiency decreases as grating area is increased. Furthermore, this work will demonstrate how to extract both the optical and neural modulation transfer functions of the human eye. The neural transfer function is found to be proportional to spatial frequency up to the local cut-off frequency at eccentricities of 0 - 37 deg across the visual field. The optical transfer function of the human eye is proposed to be more affected by the Stiles-Crawford -effect than generally assumed in the literature. Similarly, this work questions the prevailing ideas about the factors limiting peripheral vision by showing that peripheral optical acts as a low-pass filter in normal viewing conditions, and therefore the effect of peripheral optics is worse than generally assumed.

Mass transfer in fluidized bed drying of moist particulate

Bubbling fluidized bed technology is one of the most effective mean for interaction between solid and gas flow, mainly due to its good mixing and high heat and mass transfer rate. It has been widely used at a commercial scale for drying of grains such as in pharmaceutical, fertilizers and food industries. When applied to drying of non-pours moist solid particles, the water is drawn-off driven by the difference in water concentration between the solid phase and the fluidizing gas. In most cases, the fluidizing gas or drying agent is air. Despite of the simplicity of its operation, the design of a bubbling fluidized bed dryer requires an understanding of the combined complexity in hydrodynamics and the mass transfer mechanism. On the other hand, reliable mass transfer coefficient equations are also required to satisfy the growing interest in mathematical modelling and simulation, for accurate prediction of the process kinetics. This chapter presents an overview of the various mechanisms contributing to particulate drying in a bubbling fluidized bed and the mass transfer coefficient corresponding to each mechanism. In addition, a case study on measuring the overall mass transfer coefficient is discussed. These measurements are then used for the validation of mass transfer coefficient correlations and for assessing the various assumptions used in developing these correlations.

Uncatalysed and potassium-catalysed pyrolysis of the cell-wall constituents of biomass and their model compounds

Cell-wall components (cellulose, hemicellulose (oat spelt xylan), lignin (Organosolv)), and model compounds (levoglucosan (an intermediate product of cellulose decomposition) and chlorogenic acid (structurally similar to lignin polymer units)) have been investigated to probe in detail the influence of potassium on their pyrolysis behaviours as well as their uncatalysed decomposition reaction. Cellulose and lignin were pretreated to remove salts and metals by hydrochloric acid, and this dematerialized sample was impregnated with 1% of potassium as potassium acetate. Levoglucosan, xylan and chlorogenic acid were mixed with CHCOOK to introduce 1% K. Characterisation was performed using thermogravimetric analysis (TGA) and differential thermal analysis (DTA). In addition to the TGA pyrolysis, pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS) analysis was introduced to examine reaction products. Potassium-catalysed pyrolysis has a huge influence on the char formation stage and increases the char yields considerably (from 7.7% for raw cellulose to 27.7% for potassium impregnated cellulose; from 5.7% for raw levoglucosan to 20.8% for levoglucosan with CHCOOK added). Major changes in the pyrolytic decomposition pathways were observed for cellulose, levoglucosan and chlorogenic acid. The results for cellulose and levoglucosan are consistent with a base catalysed route in the presence of the potassium salt which promotes complete decomposition of glucosidic units by a heterolytic mechanism and favours its direct depolymerization and fragmentation to low molecular weight components (e.g. acetic acid, formic acid, glyoxal, hydroxyacetaldehyde and acetol). Base catalysed polymerization reactions increase the char yield. Potassium-catalysed lignin pyrolysis is very significant: the temperature of maximum conversion in pyrolysis shifts to lower temperature by 70 K and catalysed polymerization reactions increase the char yield from 37% to 51%. A similar trend is observed for the model compound, chlorogenic acid. The addition of potassium does not produce a dramatic change in the tar product distribution, although its addition to chlorogenic acid promoted the generation of cyclohexane and phenol derivatives. Postulated thermal decomposition schemes for chlorogenic acid are presented. © 2008 Elsevier B.V. All rights reserved.

Implementing collaborative practices in the healthcare supply chain:insights into hospital-vendor operations

The paper discusses the characteristics of healthcare supply chains, and puts particular emphasis on the implementation of VMI/CMI in this sector specific context. By the means of case study research the paper provides empirical data on the benefits of the above collaborative practices for both the hospital and vendors. The paper contributes to the stream of research on VMI/CMI in the healthcare sector, where limited research attempts have been conducted so far. In contrast to other surveys this case study shows that specific and measurable cost reductions exist, in addition to other improvements such as better control over the inventories, and also in reduction of administrative work. Results obtained may be also relevant to other hospitals and vendors and as they can form a basis for comparisons. Copyright © 2013 Inderscience Enterprises Ltd.

Theoretical perspectives in purchasing and supply chain management:an analysis of the literature

Purpose – This paper attempts to seek answers to four questions. Two of these questions have been borrowed (but adapted) from the work of Defee et al.: RQ1. To what extent is theory used in purchasing and supply chain management (P&SCM) research? RQ2. What are the prevalent theories to be found in P&SCM research? Following on from these questions an additional question is posed: RQ3. Are theory-based papers more highly cited than papers with no theoretical foundation? Finally, drawing on the work of Harland et al., the authors have added a fourth question: RQ4. To what extent does P&SCM meet the tests of coherence, breadth and depth, and quality necessary to make it a scientific discipline? Design/methodology/approach – A systematic literature review was conducted in accordance with the model outlined by Tranfield et al. for three journals within the field of “purchasing and supply chain management”. In total 1,113 articles were reviewed. In addition a citation analysis was completed covering 806 articles in total. Findings – The headline features from the results suggest that nearly a decade-and-a-half on from its development, the field still lacks coherence. There is the absence of theory in much of the work and although theory-based articles achieved on average a higher number of citations than non-theoretical papers, there is no obvious contender as an emergent paradigm for the discipline. Furthermore, it is evident that P&SCM does not meet Fabian's test necessary to make it a scientific discipline and is still some way from being a normal science. Research limitations/implications – This study would have benefited from the analysis of further journals, however the analysis of 1,113 articles from three leading journals in the field of P&SCM was deemed sufficient in scope. In addition, a further significant line of enquiry to follow is the rigour vs relevance debate. Practical implications – This article is of interest to both an academic and practitioner audience as it highlights the use theories in P&SCM. Furthermore, this article raises a number of important questions. Should research in this area draw more heavily on theory and if so which theories are appropriate? Social implications – The broader social implications relate to the discussion of how a scientific discipline develops and builds on the work of Fabian and Amundson. Originality/value – The data set for this study is significant and builds on a number of previous literature reviews. This review is both greater in scope than previous reviews and is broader in its subject focus. In addition, the citation analysis (not previously conducted in any of the reviews) and statistical test highlights that theory-based articles are more highly cited than non-theoretically based papers. This could indicate that researchers are attempting to build on one another's work.

Technology transfer and sustainable industrial development for developing countries

This paper reports on a part of work for the UNIDO initiative on technology transfer for sustainable industrial development. The proposed technology transfer framework, adapted from the East Asian late industrialisers model, identifies two categories of countries requiring support for enhancing their technological capabilities: (a) very late industrialisers (“low income” developing countries), and (b) slow industrialisers (countries with sizeable manufacturing sectors but limited success in gaining international competitiveness) and three technology transfer routes: (a) through trade and aid to strengthen indigenous production for domestic markets (Route 1); (b) through FDI and contracting to develop export oriented firms (Route 2), and (c) through the supply chain of capital equipment and materials to develop local subcontracting capacity (Route 3). Very late industrialisers need support to start with Route 1 in selected sectors and upgrade through imported mature technologies. Appropriate product innovations are also possible. The slow industrialisers have more scope for increased technology transfer through Routes 2 and 3.

Technology transfer and competitive operations:the valuation and collaboration questions

To improve competitiveness and find new markets companies are extending their operations through collaborations involving technology transfer. However, such collaborations have often been based on ad hoc agreements resulting from negotiations in which each side has been inadequately equipped with information about the other’s motivations and expectations. As a result there has been a gap in the ‘value’ attached to the technology, leading to delays or even failure in reaching an agreement. To address this problem a technology valuation and collaboration model has been developed using empirical data gathered from various points along the UK-China value chain for machine tool technology.

Transfer of patients from health care centres to special care services:analysis of travel distances in Nordic countries

Objectives: This paper highlights the importance of analysing patient transportation in Nordic circumpolar areas. The research questions we asked are as follows: How many Finnish patients have been transferred to special care intra-country and inter-country in 2009? Does it make any difference to health care policymakers if patients are transferred inter-country? Study design: We analysed the differences in distances from health care centres to special care services within Finland, Sweden and Norway and considered the health care policy implica tions. Methods: An analysis of the time required to drive between service providers using the "Google distance meter" (http://maps.google.com/); conducting interviews with key Finnish stakeholders; and undertaking a quantitative analyses of referral data from the Lapland Hospital District. Results: Finnish patients are generally not transferred for health care services across national borders even if the distances are shorter. Conclusion: Finnish patients have limited access to health care services in circumpolar are as across the Nordic countries for 2 reasons. First, health professionals in Norway and Sweden do not speak Finnish, which presents a language problem. Second, The Social Insurance Institution of Finland does not cover the expenditures of travel or the costs of medicine. In addition, it seems that in circumpolar areas the density of Finnish service providers is greater than Swedish ones, causing many Swedish citizens to transfer to Finnish health care providers every year. However, future research is needed to determine the precise reasons for this.

Mass transfer and chemical reaction on a distillation plate

A multistage distillation column in which mass transfer and a reversible chemical reaction occurred simultaneously, has been investigated to formulate a technique by which this process can be analysed or predicted. A transesterification reaction between ethyl alcohol and butyl acetate, catalysed by concentrated sulphuric acid, was selected for the investigation and all the components were analysed on a gas liquid chromatograph. The transesterification reaction kinetics have been studied in a batch reactor for catalyst concentrations of 0.1 - 1.0 weight percent and temperatures between 21.4 and 85.0 °C. The reaction was found to be second order and dependent on the catalyst concentration at a given temperature. The vapour liquid equilibrium data for six binary, four ternary and one quaternary systems are measured at atmospheric pressure using a modified Cathala dynamic equilibrium still. The systems with the exception of ethyl alcohol - butyl alcohol mixtures, were found to be non-ideal. Multicomponent vapour liquid equilibrium compositions were predicted by a computer programme which utilised the Van Laar constants obtained from the binary data sets. Good agreement was obtained between the predicted and experimental quaternary equilibrium vapour compositions. Continuous transesterification experiments were carried out in a six stage sieve plate distillation column. The column was 3" in internal diameter and of unit construction in glass. The plates were 8" apart and had a free area of 7.7%. Both the liquid and vapour streams were analysed. The component conversion was dependent on the boilup rate and the reflux ratio. Because of the presence of the reaction, the concentration of one of the lighter components increased below the feed plate. In the same region a highly developed foam was formed due to the presence of the catalyst. The experimental results were analysed by the solution of a series of simultaneous enthalpy and mass equations. Good agreement was obtained between the experimental and calculated results.

The need for wider supply chain management adoption:empirical results from Ireland

Purpose - This paper aims to provide empirical results which suggest that there is a need for more widespread adoption of supply chain management among Irish firms. Design/methodology/approach - The Republic of Ireland is a small, open, trade-dependent economy and is one of the fastest growing economies in the developed world. However, due to rising costs, there is an increasing trend in Ireland to outsource lower function manufacturing processes to lower-cost locations but to retain high-skill functions (such as R&D). This trend, together with other factors such as its peripheral location, suggests that supply chain management is critical from an Irish perspective. In order to gain unique insights of current levels of awareness/adoption of SCM and the potential impact SCM could have on competitiveness, a survey was conducted among 776 Irish firms. Findings - Overall, the findings suggest that many firms in Ireland pay lip-service to the importance of SCM elements and objectives but the majority of firms, about two thirds, have only a passing understanding of what constitutes SCM. Only 25 per cent adopt SCM programmes and only 9 per cent of Irish companies have a specialised SCM or logistics manager. The gaps in their understanding of SCM are matched by the gaps in their awareness of key costs (e.g. 59 per cent of companies do not know their total supply chain costs). While there are supply chain management adopters in Ireland that are already well up the s-curve of innovation transfer, it is the larger group of less aware companies that must become better at how they manage their supply chains. Originality/value - The paper offers a useful insight into supply chain management and its role in Irish industry. © Emerald Group Publishing Limited.

Green supply chain performance measurement using fuzzy ANP-based balanced scorecard:a collaborative decision-making approach

The purpose of this paper is to delineate a green supply chain (GSC) performance measurement framework using an intra-organisational collaborative decision-making (CDM) approach. A fuzzy analytic network process (ANP)-based green-balanced scorecard (GrBSc) has been used within the CDM approach to assist in arriving at a consistent, accurate and timely data flow across all cross-functional areas of a business. A green causal relationship is established and linked to the fuzzy ANP approach. The causal relationship involves organisational commitment, eco-design, GSC process, social performance and sustainable performance constructs. Sub-constructs and sub-sub-constructs are also identified and linked to the causal relationship to form a network. The fuzzy ANP approach suitably handles the vagueness of the linguistics information of the CDM approach. The CDM approach is implemented in a UK-based carpet-manufacturing firm. The performance measurement approach, in addition to the traditional financial performance and accounting measures, aids in firms decision-making with regard to the overall organisational goals. The implemented approach assists the firm in identifying further requirements of the collaborative data across the supply-cain and information about customers and markets. Overall, the CDM-based GrBSc approach assists managers in deciding if the suppliers performances meet the industry and environment standards with effective human resource. © 2013 Taylor & Francis.

An Investigation into Outsourcing Practice in Ireland:A New Direction in Logistics and Supply Chain Management

Companies are increasingly focusing on the development of core competencies as an integral part of their overall strategy development and implementation. The corollary of this is that functions regarded as being non-core are being outsourced. This paper investigates the case for and against outsourcing and in addition what is happening in Ireland regards outsourcing. Furthermore to analysis of current literature in the field, an Irish-wide postal and e-mail survey, as well as three case studies revealed many interesting facts. The key findings of the work are manufacturing outsourcing is now the most popular function to be outsourced for both small to medium sized enterprises (SMEs) and large enterprises. Large enterprises (LEs) do not prepare or examine hidden costs more than SMEs, nor do they differ much in relation to the use of consultants. Furthermore, the importance of time spent on preparing or producing contract, and the impact the contract can have on the supplier-buyer relation do not differ significantly. It was found that most companies outsourced within Ireland, which led to further investigation in that area. In relation to logistics outsourcing specifically, this has become very important in the supply chain over the last 20 years as an activity that was traditionally handled by firms as a support function. At that time logistics activities such as warehousing, distribution, transportation and inventory management were given low priority compared with other business functions within the organisation. However, since the customer has become more demanding, the logistics function has now become a source of competitive advantage and there has been a growing emphasis on providing good customer service.

A conceptual framework for supply chain collaboration:empirical evidence from the agri-food industry

Purpose - The purpose of this paper is to analyse the concept of supply chain collaboration and to provide an overall framework that can be used as a conceptual landmark for further empirical research. In addition, the concept is explored in the context of agri-food industry and particularities are identified. Finally, the paper submits empirical evidence from an exploratory case study in the agri-food industry, at the grower-processor interface, and information regarding the way the concept is actually applied in small medium-sized enterprises (SMEs) is presented. Design/methodology/approach - The paper employed case study research by conducting in-depth interviews in the two companies. Findings - Supply chain collaboration concept is of significant importance for the agri-food industry however, some constraints arise due to the nature of industry's products, and the specific structure of the sector. Subsequently, collaboration in the supply chain is often limited to operational issues and to logistics-related activities. Research limitations/implications - Research is limited to a single case study and further qualitative testing of the conceptual model is needed in order to adjust the model before large scale testing. Practical implications - Case study findings may be transferable to other similar dual relationships at the grower-processor interface. Weaker parts in asymmetric relationships have opportunities to improve their position, altering the dependence balance, by achieving product/process excellence. Originality/value - The paper provides evidence regarding the applicability of the supply chain collaboration concept in the agri-food industry. It takes into consideration not relationships between big multinational companies, but SMEs. © Emerald Group Publishing Limited.

Exploring chain, network and cluster collaborative practices:implications for SMEs

Collaboration among enterprises has been rendered as one of the most important issues in the business agenda, either as a result of the globalisation and deregulation of markets or as a result of the Information and Communication Technology (ICT) revolution. Both factors have created a business reality where success in the collaboration practices followed, may result in improvements in the competitive position of enterprises. This paper starts from the basic business activity of the individual enterprise, looks into the chain, network and cluster collaborative practices and analyses their characteristics and the implications for Small-Medium Enterprises (SMEs). In addition, it provides insights regarding the opportunities, benefits, requirements and risks related to each collaborative practice. This paper finally argues that different collaboration practices are required, as enterprises and the industrial sectors where they operate, present distinctive characteristics.