Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Application of genomics, proteomics and metabolomics in drug discovery, development and clinic

Genomics, proteomics and metabolomics are three areas that are routinely applied throughout the drug-development process as well as after a product enters the market. This review discusses all three 'omics, reporting on the key applications, techniques, recent advances and expectations of each. Genomics, mainly through the use of novel and next-generation sequencing techniques, has advanced areas of drug discovery and development through the comparative assessment of normal and diseased-state tissues, transcription and/or expression profiling, side-effect profiling, pharmacogenomics and the identification of biomarkers. Proteomics, through techniques including isotope coded affinity tags, stable isotopic labeling by amino acids in cell culture, isobaric tags for relative and absolute quantification, multidirectional protein identification technology, activity-based probes, protein/peptide arrays, phage displays and two-hybrid systems is utilized in multiple areas through the drug development pipeline including target and lead identification, compound optimization, throughout the clinical trials process and after market analysis. Metabolomics, although the most recent and least developed of the three 'omics considered in this review, provides a significant contribution to drug development through systems biology approaches. Already implemented to some degree in the drug-discovery industry and used in applications spanning target identification through to toxicological analysis, metabolic network understanding is essential in generating future discoveries.

Reliability modelling and verification of manufacturing processes based on process knowledge management

Reliability modelling and verification is indispensable in modern manufacturing, especially for product development risk reduction. Based on the discussion of the deficiencies of traditional reliability modelling methods for process reliability, a novel modelling method is presented herein that draws upon a knowledge network of process scenarios based on the analytic network process (ANP). An integration framework of manufacturing process reliability and product quality is presented together with a product development and reliability verification process. According to the roles of key characteristics (KCs) in manufacturing processes, KCs are organised into four clusters, that is, product KCs, material KCs, operation KCs and equipment KCs, which represent the process knowledge network of manufacturing processes. A mathematical model and algorithm is developed for calculating the reliability requirements of KCs with respect to different manufacturing process scenarios. A case study on valve-sleeve component manufacturing is provided as an application example of the new reliability modelling and verification procedure. This methodology is applied in the valve-sleeve component manufacturing processes to manage and deploy production resources.

Decision-making in product quality based on failure knowledge

Decision-making in product quality is an indispensable stage in product development, in order to reduce product development risk. Based on the identification of the deficiencies of quality function deployment (QFD) and failure modes and effects analysis (FMEA), a novel decision-making method is presented that draws upon a knowledge network of failure scenarios. An ontological expression of failure scenarios is presented together with a framework of failure knowledge network (FKN). According to the roles of quality characteristics (QCs) in failure processing, QCs are set into three categories namely perceptible QCs, restrictive QCs, and controllable QCs, which present the monitor targets, control targets and improvement targets respectively for quality management. A mathematical model and algorithms based on the analytic network process (ANP) is introduced for calculating the priority of QCs with respect to different development scenarios. A case study is provided according to the proposed decision-making procedure based on FKN. This methodology is applied in the propeller design process to solve the problem of prioritising QCs. This paper provides a practical approach for decision-making in product quality. Copyright © 2011 Inderscience Enterprises Ltd.

The Japanisation process in Malaysia

This thesis examines the empirical evidence for the transferability of Japanese soft technology (JST) or Japanese work organisation within two government-initiated, Malaysian-Japanese strategic alliances: PROTON and PERNEC. The government, through its Look East Policy (LEP) began in 1982, taking Japan (and South Korea) as models and partners in Malaysian economic and industrial development process, and expected these alliances to learn the good aspects of Japanese work organisations and management styles in order for them to become independent companies, both technologically and economically. The thesis found that the alliances have been successfully taking and utilising Japanese parts, components, tools, robots and machines; i.e. the 'ready-made hard technology'. [Whereas the important element of soft technology has been ignored]. The soft technology has been slowly and marginally transferred because neither local parties nor their Japanese counterparts within the alliances consider the acquisition or transfer of soft technology to be the main concern or a part of business plan. Although many factors influence management transfer, the thesis has focused on the eagerness and the capability of Malaysian managerial teams to acquire and, to a lesser extent, the readiness of the Japanese to transfer the technology. It was found that there is a lack of demand on technology acquisition by Malaysian managers and lack of responsibility to transfer the technology among Japanese experts. However, the political and social pressures on these alliances, the industrial climate and labour market, leaderships and management system of alliances, and Japanese MNCs regional and global corporate strategies have contributed to the high level of transfer of JST at PROTON compared to PERNEC. The research also found that Malaysian industrial and investment policies have favoured foreign investment but there is a lack of strategies for nurturing indigenous technological development.On the other hand the Japanese MNCs and public agencies have been operating in Malaysia and guided by their regional and global corporate strategies and less concerned with Malaysian technological development. In conclusion, empirically, the JST transfer is minimal. The transfer has been influenced by internal contingency factors of organisation; external industrial, political and cultural environmental factors; and last but not least the Japanese MNCs' global and regional corporate strategies. The transfer of Japanese management in this research is inclined towards core-periphery transfer model, it is also related to organisational and national technological capability.

The development of a modified dissolution method suitable for investigating powder mixtures

A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.

The effects of external linkages on new product innovativeness:an examination of moderating and mediating influences

Our study of 116 new product development projects in Taiwanese Information Technology (IT) firms show that horizontal linkages more strongly impact on new product innovativeness than vertical linkages. The firm's learning ability or absorptive capacity increases new product innovativeness. It also moderates the impacts of corporate and research institute linkages on new product innovativeness. Moreover, we confirm that knowledge gains mediate the positive impacts of absorptive capacity and external linkages on new product innovativeness.

Evaluating approaches to product design and sourcing decisions in multinational companies

Product design and sourcing decisions are among the most difficult and important of all decisions facing multinational manufacturing companies, yet associated decision support and evaluation systems tend to be myopic in nature. Design for manufacture and assembly techniques, for example, generally focuses on manufacturing capability and ignores capacity although both should be considered. Similarly, most modelling and evaluation tools available to examine the performance of various solution and improvement techniques have a narrower scope than desired. A unique collaboration, funded by the US National Science Foundation, between researchers in the USA and the UK currently addresses these problems. This paper describes a technique known as Design For the Existing Environment (DFEE) and an holistic evaluation system based on enterprise simulation that was used to demonstrate the business benefits of DFEE applied in a simple product development and manufacturing case study. A project that will extend these techniques to evaluate global product sourcing strategies is described along with the practical difficulties of building an enterprise simulation on the scale and detail required.

Go/no-go criteria during grocery brand development

Past research into new product screening criteria have largely centered on industrial new products. This study investigates the criteria that managers use for screening and evaluating new grocery products or brands. Theory suggests that the branding, promotional, and trade needs of grocery brands mean that screening criteria for grocery product development will differ from those applied to industrial goods. Our methodology departs from earlier research in gathering information on the accept/reject criteria during new product development rather than examining the reasons for success and failure after launch. The results endorse many findings from the extant literature on new product development. However, we highlight a set of factors that new product managers regard as important to the go/no-go decision in new grocery product or brand development that differs significantly from previous studies. From a research perspective, our study findings make an important contribution to the field by developing measurement scales for addressing NPD in the grocery sector.

Identifying innovation strategies: insights from the Greek food manufacturing sector

This paper examines the concept of innovation that is widely recognised as very important for all companies across different business sectors. The paper initially provides a review of the innovation literature in terms of types, classifications and sources of innovation that have been proposed over time. Then, the paper examines innovation in the context of the food industry, and in particular, it attempts to identify innovation strategies followed by Greek food manufacturing companies based on a specific model. Evidence from the Greek food manufacturing sector indicates that companies tend to innovate along the dimension of offerings that is more related to the traditional view of innovation (product and process innovation).

The transformational implementation of JSD process specifications via finite automata representation

Conventional structured methods of software engineering are often based on the use of functional decomposition coupled with the Waterfall development process model. This approach is argued to be inadequate for coping with the evolutionary nature of large software systems. Alternative development paradigms, including the operational paradigm and the transformational paradigm, have been proposed to address the inadequacies of this conventional view of software developement, and these are reviewed. JSD is presented as an example of an operational approach to software engineering, and is contrasted with other well documented examples. The thesis shows how aspects of JSD can be characterised with reference to formal language theory and automata theory. In particular, it is noted that Jackson structure diagrams are equivalent to regular expressions and can be thought of as specifying corresponding finite automata. The thesis discusses the automatic transformation of structure diagrams into finite automata using an algorithm adapted from compiler theory, and then extends the technique to deal with areas of JSD which are not strictly formalisable in terms of regular languages. In particular, an elegant and novel method for dealing with so called recognition (or parsing) difficulties is described,. Various applications of the extended technique are described. They include a new method of automatically implementing the dismemberment transformation; an efficient way of implementing inversion in languages lacking a goto-statement; and a new in-the-large implementation strategy.

Knowledge acquisition in international strategic alliances among Malaysian manufacturing firms

This thesis examines the process of knowledge acquisition by Malaysian manufacturing firms through their involvement in international strategic alliances. The strategic alliances can be with or without equity involvement. Firms involved with a foreign partner with equity involvement are joint venture firms while non-equity involvement are firms that engaged in contractual agreements. Using empirical evidence from 65 international alliances gathered through a survey conducted in high-technology manufacturing sectors, several factors that influence the process of knowledge acquisition are examined. The factors are: learning capacity, experience, goals, active involvement and accessibility to the foreign knowledge. Censored regression analysis and ordered probit analysis are used to analyse the effects of these factors on knowledge acquisition and its determinant parts, and the effects of knowledge acquisition and its determinants on the performance of the alliances. A second questionnaire gathered evidence relating to the factors, which encouraged tacit knowledge transfer between the foreign and Malaysian partners in international alliances. The key findings of the study are: knowledge acquisition in international strategic alliances is influenced by five determining factors; learning capacity, experience, articulated goals, active involvement and accessibility; new technology knowledge, product development knowledge and manufacturing process knowledge are influenced differently by the determining factors; knowledge acquisition and its determinant factors have a significant impact on the firm’s performance; cultural differences tend to moderate the effect on the firm’s performance; acquiring tacit knowledge is not only influenced by the five determinant factors but also by other factors, such as dependency, accessibility, trust, manufacturing control, learning methods and organisational systems; Malaysian firms involved in joint ventures tend to acquire more knowledge than those involved in contractual agreements, but joint ventures also exhibit higher degrees of dependency than contractual agreements; and the presence of R&D activity in the Malaysian partner encourages knowledge acquisition, but the amount of R&D expenditure has no effect on knowledge acquisition.

Vision2020 and the English language : a study of the role of language in national development.

The research reported here is an investigation into the problems of social and economic development of a multiethic and multicultural country which has the added challenge of adopting a non-indigenous code to facilitate the development process. Malaysia's power to negotiate outcomes favourable to the interest of the country is critical for the successful attainment of the goals and objectives of VISION2020. Therefore the mechanisms of the human resource development programme have to be efficacious. The three hypotheses of this study are as follows: 1. there is a fear that the problems and challenges posed by the development plans, have been conceptually trivialised; 2. based on (1) above there is a concern that solutions proposed are inadequate and inappropriate and 3. the outcome of both (1) and (2) can lead to the potential underachievement of national goals and objectives. The study proposes a complex model for conceptualising the problem which looks at the relationship between society and language, which any solutions proposed must take into proper consideration. The study looks at the mechanisms available for the smooth absorption of new Malaysian members to new and international communities. A large scale investigation was undertaken with the researcher functioning as a participant observer. An in-depth study of one particular educational ecology yielded approximately 38 hours of interviews and 100 questionnaires. These data were analysed both for explicit information and implicit implications. By some criteria national policies appear to be having the desired effect, and can be given a clean bill of health. By others it is clear that major adjustments would be necessary if the nation is to achieve its objectives in full. Based on the evidence gathered, thr study proposes an apprenticeship approach to training programmes for effective participation of new members in the new ecologies.

The development of heat recovery equipment from conception to commercialisation

A comprehensive survey of industrial sites and heat recovery products revealed gaps between equipment that was required and that which was available. Two heat recovery products were developed to fill those gaps: a gas-to-gas modular heat recovery unit; a gas-to-liquid exhaust gas heat exchanger. The former provided an entire heat recovery system in one unit. It was specifically designed to overcome the problems associated with existing component system of large design commitment, extensive installation and incompatibility between parts. The unit was intended to recover heat from multiple waste gas sources and, in particular, from baking ovens. A survey of the baking industry defined typical waste gas temperatures and flow rates, around which the unit was designed. The second unit was designed to recover heat from the exhaust gases of small diesel engines. The developed unit differed from existing designs by having a negligible effect on engine performance. In marketing terms these products are conceptual opposites. The first, a 'product-push' product generated from site and product surveys, required marketing following design. The second, a 'market-pull' product, resulted from a specific user need; this had a captive market and did not require marketing. Here marketing was replaced by commercial aspects including the protection of ideas, contracting, tendering and insurance requirements. These two product development routes are compared and contrasted. As a general conclusion this work suggests that it can be beneficial for small companies (as was the sponsor of this project) to undertake projects of the market-pull type. Generally they have a higher probability of success and are less capital intensive than their product-push counterparts. Development revealed shortcomings in three other fields: British Standards governing heat exchangers; financial assessment of energy saving schemes; degree day procedure of calculating energy savings. Methods are proposed to overcome these shortcomings.