Computational methods for the analysis of protein structure and function

The vast majority of known proteins have not yet been experimentally characterized and little is known about their function. The design and implementation of computational tools can provide insight into the function of proteins based on their sequence, their structure, their evolutionary history and their association with other proteins. Knowledge of the three-dimensional (3D) structure of a protein can lead to a deep understanding of its mode of action and interaction, but currently the structures of <1% of sequences have been experimentally solved. For this reason, it became urgent to develop new methods that are able to computationally extract relevant information from protein sequence and structure. The starting point of my work has been the study of the properties of contacts between protein residues, since they constrain protein folding and characterize different protein structures. Prediction of residue contacts in proteins is an interesting problem whose solution may be useful in protein folding recognition and de novo design. The prediction of these contacts requires the study of the protein inter-residue distances related to the specific type of amino acid pair that are encoded in the so-called contact map. An interesting new way of analyzing those structures came out when network studies were introduced, with pivotal papers demonstrating that protein contact networks also exhibit small-world behavior. In order to highlight constraints for the prediction of protein contact maps and for applications in the field of protein structure prediction and/or reconstruction from experimentally determined contact maps, I studied to which extent the characteristic path length and clustering coefficient of the protein contacts network are values that reveal characteristic features of protein contact maps. Provided that residue contacts are known for a protein sequence, the major features of its 3D structure could be deduced by combining this knowledge with correctly predicted motifs of secondary structure. In the second part of my work I focused on a particular protein structural motif, the coiled-coil, known to mediate a variety of fundamental biological interactions. Coiled-coils are found in a variety of structural forms and in a wide range of proteins including, for example, small units such as leucine zippers that drive the dimerization of many transcription factors or more complex structures such as the family of viral proteins responsible for virus-host membrane fusion. The coiled-coil structural motif is estimated to account for 5-10% of the protein sequences in the various genomes. Given their biological importance, in my work I introduced a Hidden Markov Model (HMM) that exploits the evolutionary information derived from multiple sequence alignments, to predict coiled-coil regions and to discriminate coiled-coil sequences. The results indicate that the new HMM outperforms all the existing programs and can be adopted for the coiled-coil prediction and for large-scale genome annotation. Genome annotation is a key issue in modern computational biology, being the starting point towards the understanding of the complex processes involved in biological networks. The rapid growth in the number of protein sequences and structures available poses new fundamental problems that still deserve an interpretation. Nevertheless, these data are at the basis of the design of new strategies for tackling problems such as the prediction of protein structure and function. Experimental determination of the functions of all these proteins would be a hugely time-consuming and costly task and, in most instances, has not been carried out. As an example, currently, approximately only 20% of annotated proteins in the Homo sapiens genome have been experimentally characterized. A commonly adopted procedure for annotating protein sequences relies on the "inheritance through homology" based on the notion that similar sequences share similar functions and structures. This procedure consists in the assignment of sequences to a specific group of functionally related sequences which had been grouped through clustering techniques. The clustering procedure is based on suitable similarity rules, since predicting protein structure and function from sequence largely depends on the value of sequence identity. However, additional levels of complexity are due to multi-domain proteins, to proteins that share common domains but that do not necessarily share the same function, to the finding that different combinations of shared domains can lead to different biological roles. In the last part of this study I developed and validate a system that contributes to sequence annotation by taking advantage of a validated transfer through inheritance procedure of the molecular functions and of the structural templates. After a cross-genome comparison with the BLAST program, clusters were built on the basis of two stringent constraints on sequence identity and coverage of the alignment. The adopted measure explicity answers to the problem of multi-domain proteins annotation and allows a fine grain division of the whole set of proteomes used, that ensures cluster homogeneity in terms of sequence length. A high level of coverage of structure templates on the length of protein sequences within clusters ensures that multi-domain proteins when present can be templates for sequences of similar length. This annotation procedure includes the possibility of reliably transferring statistically validated functions and structures to sequences considering information available in the present data bases of molecular functions and structures.

The Interplay of Power and Trust in Platform Ecosystems of the Enterprise Application Software Industry

In recent years, the formerly oligopolistic Enterprise Application Software (EAS) industry began to disintegrate into focal inter-firm networks with one huge, powerful, and multi-national plat-form vendor as the center, surrounded by hundreds or even thousands of small, niche players that act as complementors. From a theoretical point of view, these platform ecosystems may be governed by two organizing principles - trust and power. However, it is neither from a practical nor from a theoretical perspective clear, how trust and power relate to each other, i.e. whether they act as complements or substitutes. This study tries to elaborate our understanding of the relationship of trust and power by exploring their interplay using multi-dimensional conceptual-izations of trust and power, and by investigating potential dynamics in this interplay over the course of a partnership. Based on an exploratory multiple-case study of seven dyadic partner-ships between four platform vendors, and seven complementors, we find six different patterns of how trust and power interact over time. These patterns bear important implications for the suc-cessful management of partnerships between platform vendors and complementors, and clarify the theoretical debate surrounding the relationship of trust and power.

IT Offshoring and India: Some Implications

There has been a large spurt in the offshore outsourcing of Information Technology (IT) recently. India has been a major recipient of such work. There have been loud protests against the "loss" of jobs in the US as work was shifted to India. The large inflow of IT related work has also had major impact on the Indian economy. There are implications on the foreign policy level as well. While the economic implications are well known, we try to see a little of the foreign policy implications in this paper.

Financial Aspects of Transactions with FDI: Trade Credit Provision by SMEs in China

This paper will document financial aspects of transactions, and trade credit supply behavior with FDI among small and medium-sized enterprises(SMEs) based on two original surveys, conducted in four cities in China in 2003. The survey was designed to capture the nature of inter-firm transactions, trade credit and other financial conditions. Literature on FDI mainly refers to technology transfer, employment or investment. This paper focuses on the role and significance of FDI in the supply of trade credit due to its trade credit enforcement technology. Yanagawa, Ito and Watanabe [2006] developed a model which indicates that when a seller has higher enforcement technology or a buyer has richer liquidity, both trade credit and transaction volume will be increased. In this paper, we confirmed that FDI and G contributed to the provision of trade credit and had a positive external effect on trade credit enforcement towards China’s economy. (1) Sales towards FDI customers have the power to increase the trade credit ratio,even when controlling other factors such as choice of payment instrument, competitiveness, and expost default management. This implies that FDI does provide trade credit, not only because it has superior liquidity, but because it is also superior in terms of enforcement of trade credit repayment.(2) Cash constraints of the buyer influence the decisions concerning trade credit provided by the seller, as a model in Yanagawa, et al. [2006] predicted, and this implies that strategic default is a serious concern among SMEs in China. (3) Spillover effect exists in payment enforcement technology in transactions with FDI customers.

Impact of knowledge brokering on performance heterogeneity among business models

Purpose – The strategic management literature lacks a comprehensive explanation as to why seemingly similar business models in the same industry perform differently. This paper strives to explain this phenomenon. Design/methodology/approach – The model is conceptualized and accompanied by a case study on the airline industry to explain knowledge brokerage that creates value from the effective utilization of knowledge resources acquired from intra- and inter-firm environments. Findings – The model explains a cyclical view of business model flexibility in which the knowledge-based resource accumulation of the business model is spread across the intra- and inter-firm environments. Knowledge brokerage strategies from the inter- and intra-firm environments result in improved performance of the business model. The flexibility that the business model acquires is determined by how efficiently resource accumulation is aligned with its external environment. Originality/value – The paper effectively integrates the concepts of knowledge brokerage and business models from a resource accumulation-based view and simultaneously arrives at the performance heterogeneity of seemingly similar business models within the same industry. It has performance implications for firms that start out without any distinct resources of their own, or that use an imitated business model, to attain better performance through business model evolution aligned with successful knowledge brokerage strategies. It adds to the resource accumulation literature by explaining how resources can be effectively acquired to create value.

Global and local (GloCal) knowledge logistics for innovation and competitiveness. ACES Working Papers, August 2010

The increasing engagement of firms within global knowledge and production networks and their ability to source knowledge globally as well as locally (GloCally), for the development of innovation capacities will shape the future of UK's knowledge resources and its role in the global economy. Practices such as off-shoring R&D activities are widely adopted, creating challenging, and not very well understood, issues related to cross-country and inter-firm knowledge and technology flows. We seek to address the internationalisation and networking of research and innovation activities, including the roles and strategies of enterprises, universities, research centres, governments in a cross-country and inter-sectoral way, to assess the impact and the implications for sustaining and enhancing the competitiveness of UK firms and other British knowledge producers and users.

Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

Designing and managing collaborative enterprises in the automotive industry

This paper presents the findings of a recently completed research project. It sheds light upon the appropriate governance of inter-firm relationships, in order to achieve competitive success for the whole partnership and its individual members. An exploratory study in the German automotive industry using inductive Grounded Theory was conducted, in order to form a set of propositions that were then validated. The research has resulted in the consolidation of these propositions into a novel concept termed Collaborative Enterprise Governance, which draws on an inter-disciplinary body of knowledge. The core of the concept is a competence based contingency framework that helps enterprise managers in selecting the most appropriate governance strategy (i.e. enterprise structure) for an inter-firm relationships within automotive supply networks (i.e. enterprises), depending on various exogenous and endogenous factors.

The organisation of innovation: collaboration, cooperation and multifunctional groups in UK and German manufacturing

Marked differences exist between the institutional and social context for innovation in the UK and Germany. The question addressed here is how these different contexts affect the objectives and organisation of innovation in UK and German manufacturing. In particular, the paper examines the extent to which UK and German plants engage in inter-plant collaboration and cooperation and multifunctional working as part of their innovative activity, and explores the reasons for differences in these patterns of involvement. The investigation is based on a large-scale, comparative survey of manufacturing plants in the two countries. In Germany, institutional and social norms are found to encourage collaborative inter-plant innovation, but aspects of the German skills training and industrial relations systems make the adoption of more flexible internal systems more difficult. In the UK, by contrast, the more adversarial nature of inter-firm relations makes it more difficult to establish external collaborations based on mutual trust, but less restrictive labour market structures make it easier for UK plants to adopt multifunctional working. This is linked to differences in attitudes to the property rights and transaction cost problems inherent in innovation.

The EU's 'transnational power over' Central Asia:Developing and applying a structurally integrative approach to the study of the EU's power over Central Asia

This thesis challenges the consensual scholarly expectation of low EU impact in Central Asia. In particular, it claims that by focusing predominantly on narrow, micro-level factors, the prevailing theoretical perspectives risk overlooking less obvious aspects of the EU?s power, including structural aspects, and thus tend to underestimate the EU?s leverage in the region. Therefore, the thesis argues that a more structurally integrative and holistic approach is needed to understand the EU?s power in the region. In responding to this need, the thesis introduces a conceptual tool, which it terms „transnational power over? (TNPO). Inspired by debates in IPE, in particular new realist and critical IPE perspectives, and combining these views with insights from neorealist, neo-institutionalist and constructivist approaches to EU external relations, the concept of TNPO is an analytically eclectic notion, which helps to assess the degree to which, in today?s globalised and interdependent world, the EU?s power over third countries derives from its control over a combination of material, institutional and ideational structures, making it difficult for the EU?s partners to resist the EU?s initiatives or to reject its offers. In order to trace and assess the mechanisms of EU impact across these three structures, the thesis constructs a toolbox, which centres on four analytical distinctions: (i) EU-driven versus domestically driven mechanisms, (ii) mechanisms based on rationalist logics of action versus mechanisms following constructivist logics of action, (iii) agent-based versus purely structural mechanisms of TNPO, and (iv) transnational and intergovernmental mechanisms of EU impact. Using qualitative research methodology, the thesis then applies the conceptual model to the case of EU-Central Asia. It finds that the EU?s power over Central Asia effectively derives from its control over a combination of material, institutional and ideational structures, including its position as a leader in trade and investment in the region, its (geo)strategic and security-related capabilities vis-à-vis Central Asia, as well as the relatively dense level of institutionalisation of its relations with the five countries and the positive image of the EU in Central Asia as a more neutral actor.

Product innovation in a new technology based firm

This thesis examines the "state of the art" of product innovation in new technology In the UK. The roles in innovation attributed to small and large firms are examined. Growing attention is being focused upon the small firm sector as a seedbed for Innovation and government policy has been changing to encourage the entrepreneurial new technology based firm (NTBF). The novel perspective of this research results from working in such a firm. It provides a longitudinal study of the management of innovation in conjunction with the corporate strategy of the firm. Given that the researcher was a participant and observer in the firm studied, the research is akin to action research in methodology but is better described as grounded theory. Theoretical concepts are drawn from the prescriptive literature describing corporate strategy, and from the empirical literature which has evaluated new product success and failure. Models of the Innovation process are discussed and appropriate strategies and reasons for product innovation failure in NTBFs are described. The strategy, structure and new product development progress of the company are examined, using both the researcher's observations and company documents. This provides information on the methods and practices adopted for product innovation in a NTBF. The thesis analyses the performance of the firm In terms of product innovation. The models and strategies derived from the literature are then tested in the light of the experience of the company. Conclusions are drawn regarding strategies for innovation in NTBFs and about the innovation process in general. The importance of a NTBF adopting a synergistic strategy is shown. Links are established between the existence of synergy in the strategy and coupling in the management of innovation. Innovation is shown to be a laterally interdisciplinary exercise and therefore the "pipeline model" Is criticised. Finally a set of guidelines Is produced for the managers of NTBFs.

Knowledge management in knowledge intensive service networks:a strategic management approach

Purpose – The main purpose of this paper is to analyze knowledge management in service networks. It analyzes the knowledge management process and identifies related challenges. The authors take a strategic management approach instead of a more technology-oriented approach, since it is believed that managerial problems still remain after technological problems are solved. Design/methodology/approach – The paper explores the literature on the topic of knowledge management as well as the resource (or knowledge) based view of the firm. It offers conceptual insights and provides possible solutions for knowledge management problems. Findings – The paper discusses several possible solutions for managing knowledge processes in knowledge-intensive service networks. Solutions for knowledge identification/generation, knowledge application, knowledge combination/transfer and supporting the evolution of tacit network knowledge include personal and technological aspects, as well as organizational and cultural elements. Practical implications – In a complex environment, knowledge management and network management become crucial for business success. It is the task of network management to establish routines, and to build and regularly refresh meta-knowledge about the competencies and abilities that exist within the network. It is suggested that each network partner should be rated according to the contribution to the network knowledge base. Based on this rating, a particular network partner is a member of a certain knowledge club, meaning that the partner has access to a particular level of network knowledge. Such an established routine provides strong incentives to add knowledge to the network's knowledge base Originality/value – This paper is a first attempt to outline the problems of knowledge management in knowledge-intensive service networks and, by so doing, to introduce strategic management reasoning to the discussion.

Exploring the dimensions and transactional outcomes of incomplete business contracts

With an increased emphasis on outsourcing and shortening business cycles, contracts between firms have become more important. Carefully written contracts contribute to the efficiency and longevity of inter-firm relationships as they may constrain opportunism and are often a less costly governance mechanism than maintaining complex social relationships (Larson 1992). This exploratory examination adds to our understanding of how incomplete contracts affect interorganizational exchange. First, we consider the multiple dimensions of contract constraints (safeguards). We also investigate the extent that constraints affect decisions to enforce the relationship by delaying payments, and whether the decision is efficient. Finally, we examine the extent the constraints are effective (and ineffective) at reducing transaction problems associated with enforcement. Based on 971 observations of transactions using explicit, written terms and other secondary data in the context of IT transaction in The Netherlands we test our research propositions.

New dimensions on the economics of the entrepreneurial process

This thesis examines the transition of employees into entrepreneurship, with particular emphasis on the role of workplace characteristics in influencing this movement. The first main chapter examines whether the determinants of becoming an intrapreneur differ from those that support transitions into independent entrepreneurship. The results show that intrapreneurs resemble employees rather than entrepreneurs, contrary to what the entrepreneurship theory would suggest. Yet it shows that those intrapreneurs that expect to acquire an ownership stake in the business, unlike the rest of intrapreneurs, possess traditional entrepreneurial traits. Chapter 3 investigates how workers’ degree of specialisation determines their decision to found a firm. It shows that entrepreneurs emerging from small firms, i.e. generalists, transfer knowledge from more diverse aspects of the business and create firms more related to the main activity of their last employer. Workers in large firms, however, benefit from higher returns to human capital that increase their opportunity costs to switch to entrepreneurship. Since becoming an entrepreneur would make part of their specialised skills unutilised, the minimum quality of the idea at which they would be willing to leave will be higher and, therefore, entrepreneurs emerging from large firms will be of highest quality. Chapter 4 analyses whether the reason to terminate an employment contract is associated with the fact that the majority of entrepreneurs appear to set up their business after having worked for a small firm. Moreover, it studies how this pattern varies as the labour market conditions worsen. The effect of layoffs turns out to be a key driver in the entry to entrepreneurship and it is found to exert a greater effect the smaller the firm workers are dismissed from. This has been reflected in an overall larger flow of employees from small firms moving into entrepreneurship over the recession.

Supply chain "mega-trends":current status and future trends

The supply chain management (SCM) concept has become embedded in the thinking of many organisations in recent years. Originally introduced by management consultants in the early 1980s, SCM has a strong focus on integration of processes across functions within firms, as well as between the organisations that comprise the wider extended enterprise. There is a significant body of research to support the notion that the consistent delivery of value to customers is predicated on higher levels of intra-firm and inter-firm integration. Putting the supply chain integration (SCI) concept into practice is critically dependent on the ability of firms to manage material, money and information flows in a holistic manner. It also depends on the way in which relationships between key supply chain actors are managed. This article explores the “mega-trends” that are evident across most sectors and which have a potentially significant impact on the ability of organisations to put SCM theory into practice. The late Don Bowersox and his colleagues from Michigan State University introduced the idea of supply chain “mega-trends” over a decade ago in their widely cited article in the Journal of Business Logistics (Bowersox et al., 2000). This article explores the current status of these “mega-trends” in an Irish context based on research being undertaken at the National Institute for Transport and Logistics (NITL). It also identifies some key factors that are likely to impact upon progress in these key areas in the medium term.