Topological aspects of the human protein interaction network

It is currently widely accepted that the understanding of complex cell functions depends on an integrated network theoretical approach and not on an isolated view of the different molecular agents. Aim of this thesis was the examination of topological properties that mirror known biological aspects by depicting the human protein network with methods from graph- and network theory. The presented network is a partial human interactome of 9222 proteins and 36324 interactions, consisting of single interactions reliably extracted from peer-reviewed scientific publications. In general, one can focus on intra- or intermodular characteristics, where a functional module is defined as "a discrete entity whose function is separable from those of other modules". It is found that the presented human network is also scale-free and hierarchically organised, as shown for yeast networks before. The interactome also exhibits proteins with high betweenness and low connectivity which are biologically analyzed and interpreted here as shuttling proteins between organelles (e.g. ER to Golgi, internal ER protein translocation, peroxisomal import, nuclear pores import/export) for the first time. As an optimisation for finding proteins that connect modules, a new method is developed here based on proteins located between highly clustered regions, rather than regarding highly connected regions. As a proof of principle, the Mediator complex is found in first place, the prime example for a connector complex. Focusing on intramodular aspects, the measurement of k-clique communities discriminates overlapping modules very well. Twenty of the largest identified modules are analysed in detail and annotated to known biological structures (e.g. proteasome, the NFκB-, TGF-β complex). Additionally, two large and highly interconnected modules for signal transducer and transcription factor proteins are revealed, separated by known shuttling proteins. These proteins yield also the highest number of redundant shortcuts (by calculating the skeleton), exhibit the highest numbers of interactions and might constitute highly interconnected but spatially separated rich-clubs either for signal transduction or for transcription factors. This design principle allows manifold regulatory events for signal transduction and enables a high diversity of transcription events in the nucleus by a limited set of proteins. Altogether, biological aspects are mirrored by pure topological features, leading to a new view and to new methods that assist the annotation of proteins to biological functions, structures and subcellular localisations. As the human protein network is one of the most complex networks at all, these results will be fruitful for other fields of network theory and will help understanding complex network functions in general.

Implementation of network entropy algorithms on hpc machines, with application to high-dimensional experimental data

Network Theory is a prolific and lively field, especially when it approaches Biology. New concepts from this theory find application in areas where extensive datasets are already available for analysis, without the need to invest money to collect them. The only tools that are necessary to accomplish an analysis are easily accessible: a computing machine and a good algorithm. As these two tools progress, thanks to technology advancement and human efforts, wider and wider datasets can be analysed. The aim of this paper is twofold. Firstly, to provide an overview of one of these concepts, which originates at the meeting point between Network Theory and Statistical Mechanics: the entropy of a network ensemble. This quantity has been described from different angles in the literature. Our approach tries to be a synthesis of the different points of view. The second part of the work is devoted to presenting a parallel algorithm that can evaluate this quantity over an extensive dataset. Eventually, the algorithm will also be used to analyse high-throughput data coming from biology.

Describing and explaining the foreign expansion of network managing electronic business companies (NM-EBCs)

This study deals with the internationalization behavior of a new and specific type of e-business company, namely the network managing e-business company (NM-EBC). The business model of such e-business companies is based on providing a platform and applications for users to connect and interact, on gathering and channeling the inputs provided by the users, and on organizing and managing the cross-relationships of the various participants. Examples are online communities, matching platforms, and portals. Since NM-EBCs internationalize by replicating their business model in a foreign market and by building up and managing a network of users, who provide input themselves and interact with each other, they have to convince users in foreign markets to join the network and hence to adopt their platform. We draw upon Rogers’ Diffusion of Innovations Theory and Network Theory to explain the internationalization behavior of NM-EBCs. These two theories originate from neighboring disciplines and have not yet been used to explain the internationalization of firms. We combine both theories and formulate hypotheses about which strategies NM-EBCs may choose to expand abroad. To test the applicability of our theory and to gain rich data about the internationalization behavior of these firms, we carried out multiple case studies with internationally active Germany-based NM-EBCs.

Arctic network builders : the Arctic Coal Company's operations on Spitsbergen and its relationship with the environment

In 1906, two American industrialists, John Munroe Longyear and Frederick Ayer, formed the Arctic Coal Company to make the first large scale attempt at mining in the high-Arctic location of Spitsbergen, north of the Norwegian mainland. In doing so, they encountered numerous obstacles and built an organization that attempted to overcome them. The Americans sold out in 1916 but others followed, eventually culminating in the transformation of a largely underdeveloped landscape into a mining region. This work uses John Law’s network approach of the Actor Network Theory (ANT) framework to explain how the Arctic Coal Company built a mining network in this environmentally difficult region and why they made the choices they did. It does so by identifying and analyzing the problems the company encountered and the strategies they used to overcome them by focusing on three major components of the operations; the company’s four land claims, its technical system and its main settlement, Longyear City. Extensive comparison between aspects of Longyear City and the company’s choices of technology with other American examples place analysis of the company in a wider context and helps isolate unique aspects of mining in the high-Arctic. American examples dominate comparative sections because Americans dominated the ownership and upper management of the company.

Optimizing Functional Network Representation of Multivariate Time Series

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.

Approximate entropy of network parameters

We study the notion of approximate entropy within the framework of network theory. Approximate entropy is an uncertainty measure originally proposed in the context of dynamical systems and time series. We first define a purely structural entropy obtained by computing the approximate entropy of the so-called slide sequence. This is a surrogate of the degree sequence and it is suggested by the frequency partition of a graph. We examine this quantity for standard scale-free and Erdös-Rényi networks. By using classical results of Pincus, we show that our entropy measure often converges with network size to a certain binary Shannon entropy. As a second step, with specific attention to networks generated by dynamical processes, we investigate approximate entropy of horizontal visibility graphs. Visibility graphs allow us to naturally associate with a network the notion of temporal correlations, therefore providing the measure a dynamical garment. We show that approximate entropy distinguishes visibility graphs generated by processes with different complexity. The result probes to a greater extent these networks for the study of dynamical systems. Applications to certain biological data arising in cancer genomics are finally considered in the light of both approaches.

Negotiating regional futures:the successes and failures of the West Midlands Regional Development Agency Network

The introduction of Regional Development Agencies (RDAs) in the English regions in 1999 presented a new set of collaborative challenges to existing local institutions. The key objectives of the new policy impetus emphasise increased joined-up thinking and holistic regional governance. Partners were enjoined to promote cross-sector collaboration and present a coherent regional voice. This study aims to evaluate the impact of an RDA on the partnership infrastructure of the West Midlands. The RDA network incorporates a wide spectrum of interest and organisations with diverse collaborative histories, competencies and capacities. The study has followed partners through the process over an eighteen-month period and has sought to explore the complexities and tensions of partnership working 'on the ground'. A strong qualitative methodology has been employed in generating 'thick descriptions' of the policy domain. The research has probed beyond the 'rhetoric' of partnerships and explores the sensitivities of the collaboration process. A number of theoretical frameworks have been employed, including policy network theory; partnership and collaboration theory; organisational learning; and trust and social capital. The structural components of the West Midlands RDA network are explored, including the structural configuration of the network and stocks of human and social capital assets. These combine to form the asset base of the network. Three sets of network behaviours are then explored, namely, strategy, the management of perceptions, and learning. The thesis explores how the combination of assets and behaviours affect, and in turn are affected by, each other. The findings contribute to the growing body of knowledge and understanding surrounding policy networks and collaborative governance.

The network structure of Hungarian business clusters

This article investigates the attitudes to inter-firm co-operation in Hungary by analysing a special group of business networks: the business clusters. Following an overview of cluster policy, a wide range of selfproclaimed business clusters are identified. A small elite of these business networks evolves into successful, sustainable innovative business clusters. However, in the majority of cases, these consortia of interfirm co-operation are not based on a mutually satisfactory model, and as a consequence, many clusters do not survive in the longer term. The paper uses the concepts and models of social network theory in order to explain, why and under what circumstances inter-firm co-operation in clusters enhances the competitiveness of the network as a whole, or alternatively, under what circumstances the cluster remains dependent on Government subsidies. The empirical basis of the study is a thorough internet research about the Hungarian cluster movement; a questionnaire based expert survey among managers of clusters and member companies and a set of in-depth interviews among managers of self-proclaimed clusters. The last chapter analyises the applicability of social network theory in the analysis of business networks and a model involving the value chain is recommended.

Úton egy fenntartható gazdasági paradigma felé – A komplexitás befogadása a hálózati elméleteken keresztül (Towards a sustainable economic paradigm – Acceptance of the complexity through network theories)

Mára elkerülhetetlennek tűnik a gondolati váltás a gazdaságtudományok területén annak érdekében, hogy közelebb kerüljünk a hármas (gazdasági, társadalmi, környezeti) válságot előidéző problémák megoldásaihoz. A szerzők cikkükben amellett érvelnek, hogy a komplexitás befogadása kezdeti törekvésként értelmezhető azon az úton, amely a mindennapokban érzékelhető társadalmi és ökológiai problémák megoldásához vezet. Már léteznek olyan gazdaság- és vállalatelméletek, amelyek kezdik megkérdőjelezni az eddigi főáramú koncepciókat, és készek arra, hogy elveiket, elméleteiket a működési környezet bonyolultságát elfogadva alakítsák ki, és így találjanak mindennapos megoldásokat a gazdasági működésben. Ilyen például – a cikkben szereplő – IMP (Industrial Marketing and Purchasing) csoport hálózatelmélete. A szerzők azt kívánják bemutatni, hogy az ilyen hálózatelméletek alkalmasak arra, hogy a vállalatközi szférán túl is befolyásolják azt, ahogyan a vállalatok döntéseiket meghozzák és kapcsolataikat kezelik. ______ Today, it seems inevitable change of thought in the field of economics in order to get closer to solutions of problems which induced the triple (economic, social, environmental) crisis. In their article, the authors argue that the reception of complexity can be interpreted as an initial effort on the path that leads to the solutions of the everyday perceived social and ecological problems. The authors aim to present that the IMP (Industrial Marketing and Purchasing) group network theory is able to influence beyond the sphere of inter-company, that companies take their decisions and their relationships are treated.

Control of MNC environmental performance and the challenges of subsidiary network dimensions

The trend of green consumerism and increased standardization of environmental regulations has driven multinational corporations (MNCs) to seek standardization of environmental practices or at least seek to be associated with such behavior. In fact, many firms are seeking to free ride on this global green movement, without having the actual ecological footprint to substantiate their environmental claims. While scholars have articulated the benefits from such optimization of uniform global green operations, the challenges for MNCs to control and implement such operations are understudied. For firms to translate environmental commitment to actual performance, the obstacles are substantial, particularly for the MNC. This is attributed to headquarters' (HQ) control challenges (1) in managing core elements of the corporate environmental management (CEM) process and specifically matching verbal commitment and policy with ecological performance and by (2) the fact that the MNC operates in multiple markets and the HQ is required to implement policy across complex subsidiary networks consisting of diverse and distant units. Drawing from the literature on HQ challenges of MNC management and control, this study examines (1) how core components of the CEM process impact optimization of global environmental performance (GEP) and then uses network theory to examine how (2) a subsidiary network's dimensions can present challenges to the implementation of green management policies. It presents a framework for CEM which includes (1) MNCs' Verbal environmental commitment, (2) green policy Management which guides standards for operations, (3) actual environmental Performance reflected in a firm's ecological footprint and (4) corporate environmental Reputation (VMPR). Then it explains how an MNC's key subsidiary network dimensions (density, diversity, and dispersion) create challenges that hinder the relationship between green policy management and actual environmental performance. It combines content analysis, multiple regression, and post-hoc hierarchal cluster analysis to study US manufacturing MNCs. The findings support a positive significant effect of verbal environmental commitment and green policy management on actual global environmental performance and environmental reputation, as well as a direct impact of verbal environmental commitment on green policy management. Unexpectedly, network dimensions were not found to moderate the relationship between green management policy and GEP.

Who or what decides how stakeholders are optimally engaged by governance networks delivering public outcomes?

As the problems involving infrastructure delivery have become more complex and contentious, there has been an acknowledgement that these problems cannot be resolved by any one body working alone. This understanding has driven multi-sectoral collaboration and has led to an expansion of the set of actors, including stakeholders, who are now involved in delivery of infrastructure projects and services. However, more needs to be understood about how to include stakeholders in these processes and the optimal ways of developing the requisite combination of stakeholders to achieve effective outcomes. This thesis draws on stakeholder theory and governance network theory to obtain insights into how three networks delivering public outcomes within the Roads Alliance in Queensland engage with stakeholders in the delivery of complex and sensitive infrastructure services and projects. New knowledge about stakeholders will be obtained by testing a model of Stakeholder Salience and Engagement which combines and extends the stakeholder identification and salience theory (Mitchell, Agle, and Wood, 1997), ladder of stakeholder management and engagement (Friedman and Miles, 2006) and the model of stakeholder engagement and moral treatment of stakeholders (Greenwood, 2007). By applying this model, the broad research question: “Who or what decides how stakeholders are optimally engaged by governance networks delivering public outcomes?” will be addressed. The case studies will test a theoretical model of stakeholder salience and engagement which links strategic management decisions about stakeholder salience with the quality and quantity of engagement strategies for engaging different types of stakeholders. The outcomes of this research will contribute to and extend stakeholder theory by showing how stakeholder salience impacts on decisions about the types of engagement processes implemented. Governance network theory will be extended by showing how governance networks interact with stakeholders through the concepts of stakeholder salience and engagement. From a practical perspective this research will provide governance networks with an indication of how to optimise engagement with different types of stakeholders.

Which way up? Reading and drawing maps of the blogosphere

Mapping the physical world, the arrangement of continents and oceans, cities and villages, mountains and deserts, while not without its own contentious aspects, can at least draw upon centuries of previous work in cartography and discovery. To map virtual spaces is another challenge altogether. Are cartographic conventions applicable to depictions of the blogosphere, or the internet in general? Is a more mathematical approach required to even start to make sense of the shape of the blogosphere, to understand the network created by and between blogs? With my research comparing information flows in the Australian and French political blogs, visualising the data obtained is important as it can demonstrate the spread of ideas and topics across blogs. However, how best to depict the flows, links, and the spaces between is still unclear. Is network theory and systems of hubs and nodes more relevant than mass communication theories to the research at hand, influencing the nature of any map produced? Is it even a good idea to try and apply boundaries like ‘Australian’ and ‘French’ to parts of a map that does not reflect international borders or the Mercator projection? While drawing upon some of my work-in-progress, this paper will also evaluate previous maps of the blogosphere and approaches to depicting networks of blogs. As such, the paper will provide a greater awareness of the tools available and the strengths and limitations of mapping methodologies, helping to shape the direction of my research in a field still very much under development.

Rivalry within and between strategic networks : an investigation of the United States Automotive Industry

As a consequence of the increased incidence of collaborative arrangements between firms, the competitive environment characterising many industries has undergone profound change. It is suggested that rivalry is not necessarily enacted by individual firms according to the traditional mechanisms of direct confrontation in factor and product markets, but rather as collaborative orchestration between a number of participants or network members. Strategic networks are recognised as sets of firms within an industry that exhibit denser strategic linkages among themselves than other firms within the same industry. Based on this, strategic networks are determined according to evidence of strategic alliances between firms comprising the industry. As a result, a single strategic network represents a group of firms closely linked according to collaborative ties. Arguably, the collective outcome of these strategic relationships engineered between firms suggest that the collaborative benefits attributed to interorganisational relationships require closer examination in respect to their propensity to influence rivalry in intraindustry environments. Derived in large from the social sciences, network theory allows for the micro and macro examination of the opportunities and constraints inherent in the structure of relationships in strategic networks, establishing a relational approach upon which the conduct and performance of firms can be more fully understood. Research to date has yet to empirically investigate the relationship between strategic networks and rivalry. The limited research that has been completed utilising a network rationale to investigate competitive patterns in contemporary industry environments has been characterised by a failure to directly measure rivalry. Further, this prior research has typically embedded investigation in industry settings dominated by technological or regulatory imperatives, such as the microprocessor and airline industries. These industries, due to the presence of such imperatives, are arguably more inclined to support the realisation of network rivalry, through subscription to prescribed technological standards (eg., microprocessor industry) or by being bound by regulatory constraints dictating operation within particular market segments (airline industry). In order to counter these weaknesses, the proposition guiding research - Are patterns of rivalry predicted by strategic network membership? – is embedded in the United States Light Vehicles Industry, an industry not dominated by technological or regulatory imperatives. Further, rivalry is directly measured and utilised in research, thus distinguishing this investigation from prior research efforts. The timeframe of investigation is 1993 – 1999, with all research data derived from secondary sources. Strategic networks were defined within the United States Light Vehicles Industry based on evidence of horizontal strategic relationships between firms comprising the industry. The measure of rivalry used to directly ascertain the competitive patterns of industry participants was derived from the traditional Herfindahl Index, modified to account for patterns of rivalry observed at the market segment level. Statistical analyses of the strategic network and rivalry constructs found little evidence to support the contention of network rivalry; indeed, greater levels of rivalry were observed between firms comprising the same strategic network than between firms participating in opposing network structures. Based on these results, patterns of rivalry evidenced in the United States Light Vehicle Industry over the period 1993 – 1999 were not found to be predicted by strategic network membership. The findings generated by this research are in contrast to current theorising in the strategic network – rivalry realm. In this respect, these findings are surprising. The relevance of industry type, in conjunction with prevailing network methodology, provides the basis upon which these findings are contemplated. Overall, this study raises some important questions in relation to the relevancy of the network rivalry rationale, establishing a fruitful avenue for further research.

How can entrepreneurial musicians use electronic social networks to diffuse their music

Principal Topic: ''In less than ten years music labels will not exist anymore.'' Michael Smelli, former Global COO Sony/BMG MCA/QUT IMP Business Lab Digital Music Think Thanks 9 May 2009, Brisbane Big music labels such as EMI, Sony BMG and UMG have been responsible for promoting and producing a myriad of stars in the music industry over the last decades. However, the industry structure is under enormous threat with the emergence of a new innovative era of digital music. Recent years have seen a dramatic shift in industry power with the emergence of Napster and other file sharing sites, iTunes and other online stores, iPod and the MP3 revolution. Myspace.com and other social networking sites are connecting entrepreneurial artists with fans and creating online music communities independent of music labels. In 2008 the digital music business internationally grew by around 25% to 3.7 Billion US-Dollar. Digital platforms now account for around 20% of recorded music sales, up from 15 % in 2007 (IFPI Digital music report 2009). CD sales have fallen by 40% since their peak levels. Global digital music sales totalled an estimated US$ 3 Billion in 2007, an increase of 40% on 2006 figures. Digital sales account for an estimated 15% of global market, up from 11% in 2006 and zero in 2003. The music industry is more advanced in terms of digital revenues than any other creative or entertainment industry (except games). Its digital share is more than twice that of newspapers (7%), films (35) or books (2%). All these shifts present new possibilities for music entrepreneurs to act entrepreneurially and promote their music independently of the major music labels. Diffusion of innovations has a long tradition in both sociology (e.g. Rogers 1962, 2003) and marketing (Bass 1969, Mahajan et al., 1990). The context of the current project is theoretically interesting in two respects. First, the role of online social networks replaces traditional face-to-face word of mouth communications. Second, as music is a hedonistic product, this strongly influences the nature of interpersonal communications and their diffusion patterns. Both of these have received very little attention in the diffusion literature to date, and no studies have investigated the influence of both simultaneously. This research project is concerned with the role of social networks in this new music industry landscape, and how this may be leveraged by musicians willing to act entrepreneurially. Our key research question we intend to address is: How do online social network communities impact the nature, pattern and speed that music diffuses? Methodology/Key Propositions : We expect the nature/ character of diffusion of popular, generic music genres to be different from specialized, niche music. To date, only Moe & Fader (2002) and Lee et al. (2003) investigated diffusion patterns of music and these focus on forecast weekly sales of music CDs based on the advance purchase orders before the launch, rather than taking a detailed look at diffusion patterns. Consequently, our first research questions are concerned with understanding the nature of online communications within the context of diffusion of music and artists. Hence, we have the following research questions: RQ1: What is the nature of fan-to-fan ''word of mouth'' online communications for music? Do these vary by type of artist and genre of music? RQ2: What is the nature of artist-to-fan online communications for music? Do these vary by type of artist and genre of music? What types of communication are effective? Two outcomes from research social network theory are particularly relevant to understanding how music might diffuse through social networks. Weak tie theory (Granovetter, 1973), argues that casual or infrequent contacts within a social network (or weak ties) act as a link to unique information which is not normally contained within an entrepreneurs inner circle (or strong tie) social network. A related argument, structural hole theory (Burt, 1992), posits that it is the absence of direct links (or structural holes) between members of a social network which offers similar informational benefits. Although these two theories argue for the information benefits of casual linkages, and diversity within a social network, others acknowledge that a balanced network which consists of a mix of strong ties, weak ties is perhaps more important overall (Uzzi, 1996). It is anticipated that the network structure of the fan base for different types of artists and genres of music will vary considerably. This leads to our third research question: RQ3: How does the network structure of online social network communities impact the pattern and speed that music diffuses? The current paper is best described as theory elaboration. It will report the first exploratory phase designed to develop and elaborate relevant theory (the second phase will be a quantitative study of network structure and diffusion). We intend to develop specific research propositions or hypotheses from the above research questions. To do so we will conduct three focus group discussions of independent musicians and three focus group discussions of fans active in online music communication on social network sites. We will also conduct five case studies of bands that have successfully built fan bases through social networking sites (e.g. myspace.com, facebook.com). The idea is to identify which communication channels they employ and the characteristics of the fan interactions for different genres of music. We intend to conduct interviews with each of the artists and analyse their online interaction with their fans. Results and Implications : At the current stage, we have just begun to conduct focus group discussions. An analysis of the themes from these focus groups will enable us to further refine our research questions into testable hypotheses. Ultimately, our research will provide a better understanding of how social networks promote the diffusion of music, and how this varies for different genres of music. Hence, some music entrepreneurs will be able to promote their music more effectively. The results may be further generalised to other industries where online peer-to-peer communication is common, such as other forms of entertainment and consumer technologies.

A Novel Approach to Haptic Tele-operation of Aerial Robot Vehicles

We present a novel, simple and effective approach for tele-operation of aerial robotic vehicles with haptic feedback. Such feedback provides the remote pilot with an intuitive feel of the robot’s state and perceived local environment that will ensure simple and safe operation in cluttered 3D environments common in inspection and surveillance tasks. Our approach is based on energetic considerations and uses the concepts of network theory and port-Hamiltonian systems. We provide a general framework for addressing problems such as mapping the limited stroke of a ‘master’ joystick to the infinite stroke of a ‘slave’ vehicle, while preserving passivity of the closed-loop system in the face of potential time delays in communications links and limited sensor data