Dissecting the transcriptome in cardiovascular disease

The human transcriptome comprises a complex network of coding and non-coding RNAs implicated in a myriad of biological functions. Non-coding RNAs exhibit highly organized spatial and temporal expression patterns and are emerging as critical regulators of differentiation, homeostasis, and pathological states, including in the cardiovascular system. This review defines the current knowledge gaps, unmet methodological needs, and describes the challenges in dissecting and understanding the role and regulation of the non-coding transcriptome in cardiovascular disease. These challenges include poor annotation of the non-coding genome, determination of the cellular distribution of transcripts, assessment of the role of RNA processing and identification of cell-type specific changes in cardiovascular physiology and disease. We highlight similarities and differences in the hurdles associated with the analysis of the non-coding and protein-coding transcriptomes. In addition, we discuss how the lack of consensus and absence of standardized methods affect reproducibility of data. These shortcomings should be defeated in order to make significant scientific progress and foster the development of clinically applicable non-coding RNA-based therapeutic strategies to lessen the burden of cardiovascular disease

Co-creation: Moving towards a framework for creating innovation in the triple helix

The objective of the paper is to demonstrate how the theoretical ideas of Service-Dominant Logic (S-D logic) can usefully be applied to innovation through collaboration between university, industry and government. The debate around S-D logic has stimulated much discussion around three areas that are particularly pertinent in considering the co-creation of knowledge within the Triple Helix. The first area relates to understanding the nature of the resources provided by all the parties involved and the process through which they are integrated. The second area relates to interaction between the parties involved. The third and most complex area relates to how value is perceived by the different parties. This discussion leads to a proposed model of the co-creation process and four suggested research agendas: Research Agenda One, relating to the resources supplied by the parties and their integration; Research Agenda Two, concerning the interaction practices that enhance co-creation; Research Agenda Three, exploring what value propositions will motivate the different parties to co-create; and Research Agenda Four, considering how co-creation modifies the resources of the parties involved. A model of the co-creation process that encompasses these four research agendas and provides a conceptual framework to analyse Triple Helix initiatives is proposed. Some practical implications are then discussed, relating to the challenges for researchers in identifying who to co-create with and understanding what value propositions will motivate potential partners

Respecting the deal: how to manage co-opetitive actors in open innovation

Platforms like E-bay allow product seekers and providers to meet and exchange goods. On the same way in open innovation, as defined by Chesbrough, an enterprise can collect ideas from outside the company. But on E-bay, the seeker can return the product if it does not correspond to the expectations, since E-bay is the third-party actor in charge of assuring that the agreement between seekers and providers will be respected. So who does provide the same service for what concerns open innovation, where specifications might not fully defined? In this paper we shall describe the business model of an organizational structure to support the elicitation and respect of agreements between actors, who have conflicting interests but that gain from cooperating together. The concepts of the model will be illustrated to derive a set of propositions and a simple example will illustrate one of its possible instantiations. The description of our first evaluation phase shall find place at the end

Hijacking of the Pleiotropic Cytokine Interferon-γ by the Type III Secretion System of Yersinia pestis

Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague

An antidamping spin–orbit torque originating from the Berry curvature

Magnetization switching at the interface between ferromagnetic and paramagnetic metals, controlled by current-induced torques, could be exploited in magnetic memory technologies. Compelling questions arise regarding the role played in the switching by the spin Hall effect in the paramagnet and by the spin–orbit torque originating from the broken inversion symmetry at the interface. Of particular importance are the antidamping components of these current-induced torques acting against the equilibrium-restoring Gilbert damping of the magnetization dynamics. Here, we report the observation of an antidamping spin–orbit torque that stems from the Berry curvature, in analogy to the origin of the intrinsic spin Hall effect. We chose the ferromagnetic semiconductor (Ga,Mn)As as a material system because its crystal inversion asymmetry allows us to measure bare ferromagnetic films, rather than ferromagnetic paramagnetic heterostructures,eliminating by design any spin Hall effect contribution. We provide an intuitive picture of the Berry curvature origin of this antidamping spin–orbit torque as well as its microscopic modelling. We expect the Berry curvature spin–orbit torque to be of comparable strength to the spin-Hall effect-driven antidamping torque in ferromagnets interfaced with paramagnets with strong intrinsic spin Hall effect

Embracing open innovation to acquire external ideas and technologies and to transfer internal ideas and technologies outside

The objective of this dissertation is to increase understanding of how organizations can embrace open innovation in order to acquire external ideas and technologies from outside the organization, and to transfer internal ideas and technologies to outside the organization. The objective encompasses six sub-objectives, each addressed in one or more substudies. Altogether, the dissertation consists of nine substudies and a compendium summarizing the substudies. An extensive literature review was conducted on open innovation and crowdsourcing literature (substudies 1–4). In the subsequent empirical substudies, both qualitative research methods (substudies 5–7) and quantitative research methods (substudies 8–9) were applied. The four literature review substudies provided insights on the body of knowledge on open innovation and crowdsourcing. These substudies unveiled most of the influential articles, authors, and journals of open innovation and crowdsourcing disciplines. Moreover, they identified research gaps in the current literature. The empirical substudies offer several insightful findings. Substudy 5 shows how non-core ideas and technologies of a large firm can become valuable, especially for small firms. Intermediary platforms can find solutions to many pressing problems of large organizations by engaging renowned scientists from all over world (substudy 6). Intermediary platforms can also bring breakthrough innovations with novel mechanisms (substudy 7). Large firms are not only able to garner ideas by engaging their customers through crowdsourcing but they can also build long-lasting relations with their customers (substudies 8 and 9). Embracing open innovation brings challenges for firms too. Firms need to change their organizational structures in order to be able to fully benefit from open innovation. When crowdsourcing is successful, it produces a very large number of new ideas. This has the consequence that firms need to allocate a significant amount of resources in order to identify the most promising ideas. In an idea contest, customarily, only one or a few best ideas are rewarded (substudy 7). Sometimes, no reward is provided for the selected idea (substudies 8 and 9). Most of the ideas that are received are not implemented in practice

Mind the gap: Balancing alliance network and technology portfolios during periods of technological uncertainty

While clique-embeddedness is generally considered to enhance firm performance, there are also reasons to expect that under conditions of technological turbulence clique-membership is less beneficial or might even become a liability. To address this, we study the innovative performance of clique members during periods of both technological change and technological stability. We find support for the idea that companies’ ability to adapt their alliance network (i.e. forming ties beyond the scope of the clique) and their ability to adapt their technology portfolios (i.e. access to novel technological knowledge) positively influences their innovative performance during technologically turbulent periods