<em>Enterococcus faecalis</em> Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-kappa B inflammatory response as well as impaired DNA damage response and cell cycle control gene expression

The program for biodiversity research in Brazil: The role of regional networks for biodiversity knowledge, dissemination, and conservation

The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Local Political Capital for Innovation in the Global Knowledge Economy

Over the last decade, policy initiatives to promote innovativeness and growth, inspired by normative models of capacity building through industrial clusters, triple helix and innovation systems, have proliferated. Theories of economic development offer several explanations of the emergence of clusters in particular environments. Most theorists would argue that specific, natural, economic, or institutional factors determine capacity building in terms of cluster development. Other theorists emphasize the role of local social networks and phases of regional knowledge-based spaces in explaining the emergence of such capacity building. Neither of these theoretical streams offers systematic explanations of differences in the emergence and success of capacity building, beyond finding that crucial resources are unevenly distributed. The theoretical linkage between triple helix and capacity building through innovation governance is unclear. We still do not have a relevant theory explaining the influence of innovation governance involving local/regional government–industry–university relationships on capacity building leading to successful innovations. Therefore, we are making a proposal to further develop theory by focusing on capacity building through different sequences of innovation governance in relation to components of local political capital - values/norms of identity, networks and local-global relations - in the era of the global knowledge economy

Regional innovation governance : a model for complex systems of innovation and economic emergence

Over the last decade, political science has moved far from the traditional economist’s view of the government and public policy as responses to ‘market failures’. One focus of understanding public policy has been on governance, which is a concept including complex public-private interactions through networks of relationships. There is often an assumption of complex socio-economic systems underlying this concept of governance. This type of thinking has been very prevalent in discussions of innovation and economic emergence. Many public policy initiatives to promote innovativeness and growth have been inspired by normative models of capacity building through industrial clusters, triple helix and regional innovation systems. While providing important insights about network and knowledge relationships, existing models poorly explain the influence of governance on innovation and economic emergence. In order to understand the issue of risk and uncertainty in innovative entrepreneurship, we propose a conceptual model that includes the impact of governing in complex systems through innovation policy. Due to the interdependency of several actors, the centers of decision-making in innovation are nested into complex systems of governing. This means that the obviously visible indicators of innovation and growth, which are often used, do not match the theoretical linkage between entrepreneurial economic emergence and capacity building. Instead of looking at firm start-ups and patents or the immediate effects of public policy through a cost-benefit analysis, our model of innovation governance requires that we delve deeper into social and knowledge relationships at the regional level. Innovation systems represent a typical example of many organizations and/or decision-centers that are formally autonomous, but are in fact linked together by an overarching set of rules, networks and relationships in systems, defined as polycentric, based on rules/norms in use to regulate access to information and common pool resources in such systems. We therefore start from this underlying theoretical insight that innovation governance depends upon capacity building among the heterogeneous organizations (university-government-industry), each based on different attributes of norms and incentives, networks and global relationships, but nevertheless tied together by overarching rules and aims of innovation and entrepreneurship. As will be further developed in the paper, we suggest that this process of capacity building during emergence and entrepreneurial uncertainty, relay on a sequence of events explaining the success and directionality of innovation through specific institutions and an associated , subsequent, organizational structure for University-Industry-Government co-operation at the local and regional level

Governance of Regional Innovation Systems: An Evolutionary Conceptual Model of How Firms Engage

This paper draws upon insights from social science, in order to propose a conceptualization of the governance of a regional innovation system. We are specifically interested in ones initiated through public policy and aiming to stimulate the competitiveness of firms through developing new technological knowledge through collaborative research involving different organizations. We are assuming firms choose whether, when and how to collaborate.This paper proposes a conceptual model, which focuses upon the governance processes at the regional level of this translation of knowledge into innovation and entrepreneurship. The underlying argumentation for the model is built from existing research. We interpret that regional innovation governance depends upon capacity building among three heterogeneous organizations – namely university-government-industry. This represents a case of a polycentric, adaptive, complex and self-organizing system, whereby collective action is supported by norms and institutions in order to develop a region resource pool. Hence, our expectation is that our conceptual model will help explain why different outcomes are possible. The concluding section discusses a future research agenda, by going further to explore how to define and analyze the attributes (mechanisms) enabling governance of a regional innovation system as well as to analyze how public policy and firms engage

Governance of Regional Innovation Systems: An Evolutionary Conceptual Model of How Firms Engage

This paper draws upon insights from social science, in order to propose a conceptualization of the governance of a regional innovation system. We are specifically interested in ones initiated through public policy and aiming to stimulate the competitiveness of firms through developing new technological knowledge through collaborative research involving different organizations. We are assuming firms choose whether, when and how to collaborate.This paper proposes a conceptual model, which focuses upon the governance processes at the regional level of this translation of knowledge into innovation and entrepreneurship. The underlying argumentation for the model is built from existing research. We interpret that regional innovation governance depends upon capacity building among three heterogeneous organizations – namely university-government-industry. This represents a case of a polycentric, adaptive, complex and self-organizing system, whereby collective action is supported by norms and institutions in order to develop a region resource pool. Hence, our expectation is that our conceptual model will help explain why different outcomes are possible. The concluding section discusses a future research agenda, by going further to explore how to define and analyze the attributes (mechanisms) enabling governance of a regional innovation system as well as to analyze how public policy and firms engage

Triple Helix as a basis for capacity building through innovation governance

Over the last decade, policy initiatives to promote innovativeness and growth, inspired by normative models of triple helix and capacity building, have proliferated. Theories of economic development offer several explanations of the emergence of clusters in particular environments. Most theorists would argue that specific, natural, economic, or institutional factors determine capacity building in terms of cluster development. Other theorists emphasize the role of local social networks and phases of regional knowledge-based triple helix spaces in explaining the emergence of such capacity building. Neither of these theoretical streams offers systematic explanations of differences in the emergence and success of capacity building, beyond finding that crucial resources are unevenly distributed. The theoretical linkage between triple helix and capacity building through innovation governance is unclear. We still do not have a relevant theory explaining the influence of innovation governance involving local government–industry–university relationships on capacity building leading to successful innovations. Therefore, we are making a proposal to further develop the triple helix theory by focusing on capacity building through different sequences of innovation governance in relation to values/norms of identity, networks and local-global relations

Collaborative Strategies: How and Why Academic Spin-offs Interact with Engineering University Centers

This chapter follows the management and development of two KIE ventures that are academic spin-offs, in relation to collaborative strategies. The perspective is on how and why academic spin-offs continue to engage in collaborative strategies with engineering centers located at the university. The KIE ventures use the centers to access scientific and technological knowledge, as expected, but they also are interested in accessing other resources and networks to help further develop their research, product and market development. The key message is that networks with research centers at the university help shape the venture. Even after the founding phase, these KIE ventures can use collaborative strategies for research to access resources and ideas – involving scientific and technological knowledge but also market and business knowledge.The results of the chapter help us understand in particular how the venture needs to continue to access resources and ideas, even during the management and development phase of the KIE conceptual model. The KIE ventures are academic spin-offs, heavily involved in the development of technologies, and yet they greatly benefit from these university networks to access market knowledge from other, established firms, and to access business knowledge through the recruitment of experienced managers