Fine-tuning of the signalling network controlling morphogenesis and stem cell development in teeth

Tooth development is regulated by sequential and reciprocal interactions between epithelium and mesenchyme. The molecular mechanisms underlying this regulation are conserved and most of the participating molecules belong to several signalling families. Research focusing on mouse teeth has uncovered many aspects of tooth development, including molecular and evolutionary specifi cs, and in addition offered a valuable system to analyse the regulation of epithelial stem cells. In mice the spatial and temporal regulation of cell differentiation and the mechanisms of patterning during development can be analysed both in vivo and in vitro. Follistatin (Fst), a negative regulator of TGFβ superfamily signalling, is an important inhibitor during embryonic development. We showed the necessity of modulation of TGFβ signalling by Fst in three different regulatory steps during tooth development. First we showed that tinkering with the level of TGFβ signalling by Fst may cause variation in the molar cusp patterning and crown morphogenesis. Second, our results indicated that in the continuously growing mouse incisors asymmetric expression of Fst is responsible for the labial-lingual patterning of ameloblast differentiation and enamel formation. Two TGFβ superfamily signals, BMP and Activin, are required for proper ameloblast differentiation and Fst modulates their effects. Third, we identifi ed a complex signalling network regulating the maintenance and proliferation of epithelial stem cells in the incisor, and showed that Fst is an essential modulator of this regulation. FGF3 in cooperation with FGF10 stimulates proliferation of epithelial stem cells and transit amplifying cells in the labial cervical loop. BMP4 represses Fgf3 expression whereas Activin inhibits the repressive effect of BMP4 on the labial side. Thus, Fst inhibits Activin rather than BMP4 in the cervical loop area and limits the proliferation of lingual epithelium, thereby causing the asymmetric maintenance and proliferation of epithelial stem cells. In addition, we detected Lgr5, a Wnt target gene and an epithelial stem cell marker in the intestine, in the putative epithelial stem cells of the incisor, suggesting that Lgr5 is a marker of incisor stem cells but is not regulated by Wnt/β-catenin signalling in the incisor. Thus the epithelial stem cells in the incisor may not be directly regulated by Wnt/β-catenin signalling. In conclusion, we showed in the mouse incisors that modulating the balance between inductive and inhibitory signals constitutes a key mechanism regulating the epithelial stem cells and ameloblast differentiation. Furthermore, we found additional support for the location of the putative epithelial stem cells and for the stemness of these cells. In the mouse molar we showed the necessity of fi ne-tuning the signalling in the regulation of the crown morphogenesis, and that altering the levels of an inhibitor can cause variation in the crown patterning.

Investigations of planetary boundary layer processes and particle formation in the atmosphere of planet Mars

The planet Mars is the Earth's neighbour in the Solar System. Planetary research stems from a fundamental need to explore our surroundings, typical for mankind. Manned missions to Mars are already being planned, and understanding the environment to which the astronauts would be exposed is of utmost importance for a successful mission. Information of the Martian environment given by models is already now used in designing the landers and orbiters sent to the red planet. In particular, studies of the Martian atmosphere are crucial for instrument design, entry, descent and landing system design, landing site selection, and aerobraking calculations. Research of planetary atmospheres can also contribute to atmospheric studies of the Earth via model testing and development of parameterizations: even after decades of modeling the Earth's atmosphere, we are still far from perfect weather predictions. On a global level, Mars has also been experiencing climate change. The aerosol effect is one of the largest unknowns in the present terrestrial climate change studies, and the role of aerosol particles in any climate is fundamental: studies of climate variations on another planet can help us better understand our own global change. In this thesis I have used an atmospheric column model for Mars to study the behaviour of the lowest layer of the atmosphere, the planetary boundary layer (PBL), and I have developed nucleation (particle formation) models for Martian conditions. The models were also coupled to study, for example, fog formation in the PBL. The PBL is perhaps the most significant part of the atmosphere for landers and humans, since we live in it and experience its state, for example, as gusty winds, nightfrost, and fogs. However, PBL modelling in weather prediction models is still a difficult task. Mars hosts a variety of cloud types, mainly composed of water ice particles, but also CO2 ice clouds form in the very cold polar night and at high altitudes elsewhere. Nucleation is the first step in particle formation, and always includes a phase transition. Cloud crystals on Mars form from vapour to ice on ubiquitous, suspended dust particles. Clouds on Mars have a small radiative effect in the present climate, but it may have been more important in the past. This thesis represents an attempt to model the Martian atmosphere at the smallest scales with high resolution. The models used and developed during the course of the research are useful tools for developing and testing parameterizations for larger-scale models all the way up to global climate models, since the small-scale models can describe processes that in the large-scale models are reduced to subgrid (not explicitly resolved) scale.

Search for standard model Higgs boson production in association with a W boson using a neural network discriminant at CDF

We present a search for standard model Higgs boson production in association with a W boson in proton-antiproton collisions at a center of mass energy of 1.96 TeV. The search employs data collected with the CDF II detector that correspond to an integrated luminosity of approximately 1.9 inverse fb. We select events consistent with a signature of a single charged lepton, missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with a secondary vertex tagging method, a jet probability tagging method, and a neural network filter. We use kinematic information in an artificial neural network to improve discrimination between signal and background compared to previous analyses. The observed number of events and the neural network output distributions are consistent with the standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching fraction ranging from 1.2 to 1.1 pb or 7.5 to 102 times the standard model expectation for Higgs boson masses from 110 to $150 GeV/c^2, respectively.

Conflicts when Competitors Cooperate: Exploring Elements of Conflicts from a Business Network Perspective

Most of the existing research within the business network approach is based on companies that are operating on different levels within the same value chain, as a buyer and a supplier. Intercompetitor cooperation, i.e. cooperation between companies occupying the same level within different value chains, has not been studied to the same extent. Moreover scholars within the business network approach have usually described industrial relationships as long term, consisting of mutual commitment and trust. Industrial relationships are not static, but dynamic, and they contain situations of both harmony and conflict. There is consequently a need for more research both concerning intercompetitor cooperation and conflicts. The purpose of this study is to develop our theoretical and empirical understanding of the nature of conflicts in intercompetitor cooperation from a business network perspective. The focus of the study lies on issue and intensity of conflict. The issue of a conflict can be divided into cause and topic, while the intensity comprises the importance and outcome of a conflict. The empirical part of the study is based on two case studies of groups of cooperating competitors from two different industries. The applied research method is interviews. According to the findings of this study causes of conflicts in intercompetitor cooperation can be divided into three groups: focus, awareness and capacity. Topics of conflict can be related to domain, delivery, advertising or cooperation. Moreover the findings show that conflict situations may be grouped into not important, important or very important. Some conflicts may also be of varying importance, meaning that the importance varies from one point of time to another. Based on the findings of the study the outcome or status of a conflict can be analyzed both on a concrete and general level. The findings also indicate that several conflicts are partly hidden, which means that only one or some of the involved actors perceive the conflict. Furthermore several conflict situations can be related to external network actors.

Adaptation in a Business Network Cooperation Context (summary section only)

In today’s business one can say that competition does not take place inside the network, but between networks. Change and dynamics are central issues in network studies, and a company, due its changing environment, can identify opportunities and threats and respond to them accordingly. These opportunities are vital, but also complex and demanding for the management. Earlier research has identified a shortcoming in explanations of how the micro-level interactions to macro-level patterns are connected. The IMP-group has been trying to fill this research gap with research on interactions within business networks. In this area of research lies the focus of research on relationships between organizations. Adaptation in cooperation is a central concept within business network research. Adaptation has been dealt with in previous literature, but the focus of the studies has mainly been outside this phenomenon, and it has mostly had a supporting role. Most literature has also described the buyers' point of view in studied supply networks, whereas much less attention has been paid to the suppliers' view on them. This study focuses on this research gap. The results of the study stress that adaptation should be included to a greater extent in the strategy work of companies. The adaptations should be carefully planned and, as far as possible, made consciously. Conscious, well-planned adaptations can be seen as investments into present and future relationships, and resources should be invested into something that does not increase the company’s dependence, but divides the power in the relationship between the companies. Adaptations should be planned so that they result in a more offensive way of responding to the demands that are placed upon the companies. In this way, the actions can be viewed and analyzed in accordance with whether the actions make the company weaker or stronger.

Collective Network Capability in International Project Business Networks - A Case Study of the Business Network for the Ashanti Electrification Project in Ghana

Despite thirty years of research in interorganizational networks and project business within the industrial networks approach and relationship marketing, collective capability of networks of business and other interorganizational actors has not been explicitly conceptualized and studied within the above-named approaches. This is despite the fact that the two approaches maintain that networking is one of the core strategies for the long-term survival of market actors. Recently, many scholars within the above-named approaches have emphasized that the survival of market actors is based on the strength of their networks and that inter-firm competition is being replaced by inter-network competition. Furthermore, project business is characterized by the building of goal-oriented, temporary networks whose aims, structures, and procedures are clarified and that are governed by processes of interaction as well as recurrent contracts. This study develops frameworks for studying and analysing collective network capability, i.e. collective capability created for the network of firms. The concept is first justified and positioned within the industrial networks, project business, and relationship marketing schools. An eclectic source of conceptual input is based on four major approaches to interorganizational business relationships. The study uses qualitative research and analysis, and the case report analyses the empirical phenomenon using a large number of qualitative techniques: tables, diagrams, network models, matrices etc. The study shows the high level of uniqueness and complexity of international project business. While perceived psychic distance between the parties may be small due to previous project experiences and the benefit of existing relationships, a varied number of critical events develop due to the economic and local context of the recipient country as well as the coordination demands of the large number of involved actors. The study shows that the successful creation of collective network capability led to the success of the network for the studied project. The processes and structures for creating collective network capability are encapsulated in a model of governance factors for interorganizational networks. The theoretical and management implications are summarized in seven propositions. The core implication is that project business success in unique and complex environments is achieved by accessing the capabilities of a network of actors, and project management in such environments should be built on both contractual and cooperative procedures with local recipient country parties.

Power and Distribution Network Structure in the People's Republic of China - The Case of an Inland City in Transition

The aim of the current study is to examine the influence of the channel external environment on power, and the effect of power on the distribution network structure within the People’s Republic of China. Throughout the study a dual research process was applied. The theory was constructed by elaborating the main theoretical premises of the study, the channel power theories, the political economy framework and the distribution network structure, but these marketing channel concepts were expanded with other perspectives from other disciplines. The main method applied was a survey conducted among 164 Chinese retailers, complemented by interviews, photographs, observations and census data from the field. This multi-method approach enabled not only to validate and triangulate the quantitative results, but to uncover serendipitous findings as well. The theoretical contribution of the current study to the theory of marketing channels power is the different view it takes on power. First, earlier power studies have taken the producer perspective, whereas the current study also includes a distributor perspective to the discussion. Second, many power studies have dealt with strongly dependent relationships, whereas the current study examines loosely dependent relationships. Power is dependent on unequal distribution of resources rather than based on high dependency. The benefit of this view is in realising that power resources and power strategies are separate concepts. The empirical material of the current study confirmed that at least some resources were significantly related to power strategies. The study showed that the dimension resources composed of technology, know-how and knowledge, managerial freedom and reputation was significantly related to non-coercive power. Third, the notion of different outcomes of power is a contribution of this study to the channels power theory even though not confirmed by the empirical results. Fourth, it was proposed that channel external environment other than the resources would also contribute to the channel power. These propositions were partially supported thus providing only partial contribution to the channel power theory. Finally, power was equally distributed among the different types of actors. The findings from the qualitative data suggest that different types of retailers can be classified according to the meaning the actors put into their business. Some are more business oriented, for others retailing is the only way to earn a living. The findings also suggest that in some actors both retailing and wholesaling functions emerge, and this has implications for the marketing channels structure.

Network Knowledge versus Cluster Knowledge- The Gordian Knot of Knowledge Transfer Concepts

Both management scholars and economic geographers have studied knowledge and argued that the ability to transfer knowledge is critical to competitive success. Networks and other forms for cooperation are often the context when analyzing knowledge transfer within management research, while economic geographers focus on the role of the cluster for knowledge transfer and creation. With the common interest in knowledge transfer, few attempts to interdisciplinary research have been made. The aim of this paper is to outline the knowledge transfer concepts in the two strands of literature of management and economic geography (EG). The paper takes an analytical approach to review the existing contributions and seek to identify the benefits of further interaction between the disciplines. Furthermore, it offers an interpretation of the concepts of cluster and network, and suggests a clearer distinction between their respective definitions. The paper posits that studies of internal networks transcending national borders and clusters are not necessarily mutually exclusive when it comes to transfer of knowledge and the learning process of the firm. Our conclusion is that researchers in general seem to increasingly acknowledge the importance of studying both the effect of and the need for geographical proximity and external networks for the knowledge transfer process, but that there exists equivocalness in defining clusters and networks.