Recent advances in TIS research: towards a new phase in transition studies

The technological innovation systems (TIS) approach has become one of the key frameworks for the study of emerging technologies in and beyond the context of sustainability transitions. It focuses on understanding the dynamics of an innovation system associated with a specific technology. The approach is often used to assess the performance of a TIS, to identify shortcomings and to derive policy recommendations for the support of a selected technology (Bergek et al., 2008; Hekkert and Negro, 2009). Since its inception, the framework has seen several conceptual developments, including a clarification of scoping issues, TIS functions as a central tool for performance assessment, a strategic perspective on system building, international and global ties within TIS, and suggestions for the analysis of TIS contexts (Bergek et al., 2015; Binz et al., 2014; Markard et al., 2015). At the same time, however, there are also new conceptual challenges, especially when the TIS is used for sustainability transition studies. One of these challenges is how to study whole system reconfigurations, i.e. to move beyond the focus on specific technologies. Ongoing transitions such as the energy transition currently enter into a new phase of accelerated development, in which multiple emerging and mature technologies interact. Other conceptual challenges include the decline of incumbent technologies, intensified struggles among actors or transition processes transcending sectoral and national boundaries

PI3Kγ Protects from Myocardial Ischemia and Reperfusion Injury through a Kinase-Independent Pathway

BACKGROUND: PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR) agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD) knock-in mice, and control wild type (WT) mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R) injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK) pathway (AKT/ERK1/2) and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD) knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. CONCLUSIONS/SIGNIFICANCE: Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution

From green technology development to green innovation: inducing regulatory adoption of pathogen detection technology for sustainable forestry

Technological entrepreneurship has been widely acknowledged as a key driver of modern industrial economies, and more recently, a panacea for environmental and social problems. However, our current understanding of how green-technology ventures emerge and diffuse more sustainable innovations remains limited. We advance theory on green entrepreneurship by drawing on institutional work to refine and extend our understanding of how entrepreneurs may influence government policies and practices in their attempts to diffuse green technology. We develop a theoretical framework that combines institutional work with a search tool, the technological, commercial, organizational, and societal (TCOS) framework of innovative uncertainties, which identifies key opportunities, hurdles, and potential unintended consequences at early stages of technology development. We present a detailed case study of a potential university-based green-tech venture developing pathogen detection technology for forestry protection. Foreign pathogens spread by international trade can have major detrimental impacts on forests and the industries that rely on them. Our analysis found that green technology demonstrating technological feasibility is necessary but not sufficient; green-tech ventures must also engage in institutional work, in this case, articulating the technology’s benefits to regulators to establish legitimacy and avoid misuse that can hinder its adoption. We thus add to previous studies by emphasizing that institutional work could be a main activity for a green-tech venture, a core entrepreneurial strategy rather than an afterthought

Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion

Short non-lethal ischemic episodes administered to hearts prior to (ischemic preconditioning, IPC) or directly after (ischemic postconditioning, IPost) ischemic events facilitate myocardial protection. Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults. We propose that coronary IPC effluent contains hydrophobic cytoprotective mediators acting via PI3K/Akt-dependent pro-survival signaling at ischemic reperfusion. Ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. IPC effluent administered for 10 min prior to index ischemia attenuated infarct size by ≥55% versus control hearts (P < 0.05). Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05). The IPC effluent significantly increased Akt phosphorylation in un-preconditioned hearts when administered before ischemia or at reperfusion, while pharmacological inhibition of PI3K/Akt-signaling at reperfusion completely abrogated the cardioprotection offered by effluent administration. Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05). The total hydrophobic effluent fraction significantly reduced infarct size independently of temporal administration (before ischemia, at reperfusion or as remote postconditioning). In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion

Translating cardioprotection for patient benefit: Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology

Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Despite current therapy, the morbidity and mortality for patients with CHD remains significant. The most important manifestations of CHD arise from acute myocardial ischaemia-reperfusion injury (IRI) in terms of cardiomyocyte death and its long-term consequences. As such, new therapeutic interventions are required to protect the heart against the detrimental effects of acute IRI and improve clinical outcomes. Although a large number of cardioprotective therapies discovered in pre-clinical studies have been investigated in CHD patients, few have been translated into the clinical setting, and a significant number of these have failed to show any benefit in terms of reduced myocardial infarction and improved clinical outcomes. Because of this, there is currently no effective therapy for protecting the heart against the detrimental effects of acute IRI in patients with CHD. One major factor for this lack of success in translating cardioprotective therapies into the clinical setting can be attributed to problems with the clinical study design. Many of these clinical studies have not taken into consideration the important data provided from previously published pre-clinical and clinical studies. The overall aim of this ESC Working Group Cellular Biology of the Heart Position Paper is to provide recommendations for optimizing the design of clinical cardioprotection studies, which should hopefully result in new and effective therapeutic interventions for the future benefit of CHD patients

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research

Innovation system building: on the role of actors, networks and resources. The case of stationary fuel cells in Germany

In the field of energy supply, various innovative technologies such as fuel cells, photovoltaics and biomass digestion exist as potentially sustainable alternatives. However, many of these new technologies only cover small percentages of the overall energy supply. A better understanding of the determinants of innovations is thus crucial for their timely diffusion and a subsequent transformation of the energy sector towards more sustainable technologies. To examine the complex dynamics of technological change, the concept of technological innovation systems (TIS) represents a fruitful approach. TIS studies focus on the interplay of actors, networks and institutions and reveal systemic blocking or enhancing mechanisms that impact the generation, utilization and diffusion of new technologies. In this stream of literature, agency and the structural build-up of TIS have not been a focus point, despite their significance for innovation processes. This dissertation explores the relationships between the strategic moves of actors and the development of new technological fields. To address this question, we draw on ideas and concepts from the strategic management and entrepreneurship literature and combine them with the innovation systems perspective. In particular we focus on resources and their role in innovation system-building. The empirical field of inquiry is the innovation system on stationary fuel cells in Germany. Through in-depth interviews with key informants directly involved in system-building, we studied the strategies of firms and formal networks in the field. The field of stationary fuel cells in Germany represents a very interesting case, as the technology is not only important for the development of a smart energy system but also indicative of many technological and organizational problems currently faced by (energy) innovations as they progress from prototypes to a mass market. Our analysis revealed how key actors and networks strategically influenced the emergence of the TIS and shaped the structures of the new field. They created technological standards, lobbied for public support programs, set up commonly available training modules, created value chains and increased public awareness of fuel cells. These structures represent assets that are of strategic value for firms interested in the novel technology. We conceptualize them as system resources. Our research shows that some specific actors, which we refer to as system builders, have continuously pushed the development of collective resources at the network and system level. Network resources such as joint knowledge, reputation, power and governance structures, in addition to the aforementioned system resources, are strategically developed and deployed to influence and control the development of the innovation system as a whole