The functional performance of the αI domain α7 helix in β2 integrin activation depends on the allostery of the α7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α7 helix. Molecular dynamics (MD) simulations for three β2 integrin members, lymphocyte function-associated antigen-1 (LFA-1; αL β2 ), macrophage-1 antigen (Mac-1; αM β2 ) and αx β2 , indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery. The disruption of the salt bridge interaction, especially with double mutations in both salt bridges, significantly reduced the force-induced allostery time for all three members. The effects of salt bridge interactions of the αI domain α7 helix on β2 integrin conformational stability and allostery were experimentally validated using Mac-1 constructs. The results demonstrated that salt bridge mutations did not alter the conformational state of Mac-1, but they did increase the force-induced ligand binding and shear resistance ability, which was consistent with MD simulations. This study offers new insight into the importance of salt bridge interaction constraints of the αI domain α7 helix and external force for β2 integrin function.
Etzkowitz and Leydesdorff initially argued that the strength of the interactions between governments, industry and university depends on which component is the driving force in the framework. In a statist model, a strong state is driving interactions between the three components in a top-down implementation.[13] It creates stronger ties and a more integrated model. In a laissez-faire model, in which the industry and market forces are the leading forces, the ties are weaker and each institution tends to remain very independent. However, the distinction between the two models is not always clear cut, as the government can choose to adopt a strong or a weak stance depending on the context and the industry.[6] Strength of interactions can also vary according to the development of a country, with a silo model predominating in an underdeveloped country, moderate interactions developing in a middle-income country due to the push for economic growth on the one hand and the pull for a competitive market-driven technological advancement on the other, and strong interactions developing in a developed country, for example in the form of a science park.[16] In a recent paper, Etzkowitz emphasized that the shift towards a knowledge-based society has given a bigger role to universities. Indeed, as innovation is increasingly based on scientific knowledge, the role of universities as creators of knowledge is more valued.[17] As a result, he argues that university, industry and government are more equal,[5] and that no particular element is necessarily the driving force of the triple helix model of innovation.
Helix Academy 01 The New 18
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The triple helix model of innovation also blurred the boundaries of the traditional basic roles of university, industry and government. According to Etzkowitz and Leydesdorff, this marks the second step in the triple helix of innovation framework.[17] For example, universities increasingly take part in commercial activity through patenting and licensing, moving beyond the production of basic research. The next step is the emergence of intermediaries between the three elements as well as the hybridization of the three entities.[9] Nevertheless, each entity retains a strong primacy in its original field of expertise: the university remains the main source of knowledge production, industry is the primary vehicle of commercialization and the government retains its regulatory role.
Building on the triple helix model, the quadruple helix model adds a fourth component to the framework of interactions between university, industry and government: the public, consisting of civil society and the media.[3][20] It was first suggested in 2009 by Elias G. Carayannis and David F.J. Campbell.[21] The framework aims to bridge the gaps between innovation and civil society, and it claims that under the triple helix model, the emerging technologies do not always match the demands and needs of society, thus limiting their potential impact. The framework consequently emphasizes a societal responsibility of universities, in addition to their role of educating and conducting research. The quadruple helix is the approach that the European Union has intended to take for the development of a competitive knowledge-based society.[22] Subsequently, the quadruple helix has been applied to European Union-sponsored projects and policies, including the EU-MACS (EUropean MArket for Climate Services) project,[23] a follow-up project of the European Research and Innovation Roadmap for Climate Services, and the European Commission's Open Innovation 2.0 (OI2) policy for a digital single market that supports open innovation.[24]
The quintuple helix model was co-developed by Elias G. Carayannis and David F.J. Campbell in 2010.[3] It is based on the triple and quadruple helix models and adds as fifth helix the natural environment. The quintuple helix views the natural environments of society and the economy as drivers for knowledge production and innovation, thus defining socio-ecological opportunities for the knowledge society and knowledge economy, such as innovation to address sustainable development, including climate change.[25] The quintuple helix can be described in terms of the models of knowledge that it extends, the five subsystems (helices) it incorporates, and the steps involved in the circulation of knowledge.[26] How to define both the quadruple and quintuple helices has been debated, and some researchers see them as additional helices, while others see them as different types of helix which overarch the previous helices.[27][28]
The triple helix model has been used as a lens through which evolving relationships between university, industry and government can be analyzed.[3] However, according to Etzkowitz and Leydesdorff, it can also be a policy making tool. It has been applied for both purposes by government organizations, such as the United States Department of Energy.[29] Etzkowitz argues that after the end of the Soviet Era, triple helix inspired policies were implemented in Eastern Europe to promote their growth. In Sweden, the triple helix policy aimed at tying together innovation initiatives at different scales to increase their overall efficiency.[5][6] The triple helix model has also been applied to developing countries and regions.[8]
The triple helix model as a policy-making tool for economic growth and regional development has been criticized by many scholars.[3] One main criticism is that Etzkowitz and Leydesdorff's framework was developed within Western developed countries, which means that it is based on a particular set of infrastructures and under circumstances. For instance, the model takes for granted that knowledge intensive activities are linked to economic growth, that intellectual property rights will be protected, and that the state has a democratic and market oriented culture.[30] Further scholarly criticism of the model focuses on the conditions that enable the implementation of a triple helix innovation policy. It argues that Etzkowitz and Leydesdorff's model is too vague and takes for granted those necessary preconditions within their model.[31][32] Therefore, according to critics, the triple helix model is not a relevant policy making tool for developing countries where at least one of these conditions is missing. However, others have argued that the triple helix model is capable of both describing the situation in developing countries and is useful for planning policy.[8]
Based on the actual vane-loaded tape helix slow wave structure, a new theoretical analytic model for calculating coupling impedance is proposed by Chen Qingyou, et al.(1999) with calculated values of dispersion in good agreement with measured ones. In this paper, it is continued to use this model to calculate the coupling impedance of such a structure, and analyze the effects of the propagation power within vane gaps and the helix gap on the coupling impedance. As a result, the theoretical values are found to be in good agreement with the measured ones, with the maximum difference less than 18%. 2ff7e9595c
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