Quadruple Helices Research Articles

Application of the concepts of triple, quadruple and quintuple helices: a pilot project addressing the university-company relationship, innovation and entrepreneurship and the dissemination of technological knowledge

The importance of the university-company relationship has been growing in innovation studies, as the university is a great source of information for the innovative needs of companies. The objective of this work was to discuss the university-company relationship, considering the concepts of triple, quadruple and quintuple helix as factors that promote innovation. The methodology used was based on a systematic literature review, which presents a synthesis of the multiple articles evaluated and used. The evaluated results made it possible to highlight numerous advantages, barriers, facilitators and aspects that stimulate this relationship. Furthermore, it was possible to see how innovation, entrepreneurship and technological knowledge are important in the university-company relationship, showing that there is a need to stimulate this relationship with the aim of reducing the relationship barriers identified, as, in the current context of globalization and high-level technology development, this cooperation is of great importance for the country, positively influencing technological advances.

Learning in Cities from Within and Across Cities: A Scoping Review

Abstract Cities evolve rapidly while providing both opportunities and posing challenges. To cope with the emerging behaviours of cities, contextual innovations and development are essential. Driving innovations through the learning of contextual knowledge in cities is crucial. In this study, we explore relevant studies to identify the frameworks for human-centric innovations in cities that consider learning from within and/or across cities. We analyse how learning in cities has been addressed in those studies and find that even though some aspects of learning in cities have been studied, a comprehensive framework for how cities can learn as an innovation ecosystem is missing. Based on the findings of a scoping review and insights from the theories of the Triple, Quadruple and Quintuple helices of innovation, we present a high-level conceptual model for cities as innovation ecosystems. The model is aimed to support sustainable human-centric development through the understanding of city learning through multilevel interactions and feedback.

Computing the electronic circular dichroism spectrum of DNA quadruple helices of different topology: A critical test for a generalized excitonic model based on a fragment diabatization.

In this study, we exploit a recently developed fragment diabatization-based excitonic model, FrDEx, to simulate the electronic circular dichroism (ECD) spectra of three guanine-rich DNA sequences arranged in guanine quadruple helices with different topologies: thrombin binding aptamer (antiparallel), c-Myc promoter (parallel), and human telomeric sequence (3+1 hybrid). Starting from time-dependent density functional theory (TD-DFT) calculations with the M052X functional, we apply our protocol to parameterize the FrDEX Hamiltonian, which accounts for electron density overlap and includes both the coupling with charge transfer transitions and the effect of the surrounding bases on the local excitation of each chromophore. The TD-DFT/M052X spectral shapes are in good agreement with the experimental ones, the main source of discrepancy being related to the intrinsic error on the computed transition energies of guanine monomer. FrDEx spectra are fairly close to the reference TD-DFT ones, allowing a significant advance with respect to a more standard excitonic Hamiltonian. We also show that the ECD spectra are sensitive to the inclusion of the inner K cation in the calculation.

Have Quadruple and Quintuple Helices Emerged? Metaphors, Project Titles, and Empirical Research

Abstract In the original Triple Helix model (Etzkowitz and Leydesdorff 1995), the three “helices” of Universities, Industry and Government and the (3-way) interactions among and between them were proposed as a basis for looking at how entrepreneurship comes into being. Since the original article, other “helix-based” models have been proposed. Some vary the triple and others propose higher numbers of helix – with 4 and 5as the most typical extensions. In the article “Triple, Quadruple, and Higher-Order Helices: Historical phenomena and (neo-)evolutionary models,” Leydesdorff and Lawton Smith (2022) developed an Information-Theory based approach to look more formally at the need for higher-order helices. In the case of two helices, processes of mutual shaping can generate historical trajectories that could have been otherwise: other options providing possible states, which have not yet historically been realized (Petersen et al., 2016). Adding a third helix makes a substantive change from an information point of view: a Triple Helix model is not just the sum of three sets of 2-way interactions. However, once this number has been reached further additions can be decomposed into sets of triads (Batagelj et al., 2014; Simmel, 1902). This leads to the suggestion that higher-dimensional helix structures potentially add little to discourse. Four (sets of) authors were asked by the Editors of the Triple Helix to respond to Leydesdorff and Lawton Smith (2022). Many insightful and interesting points were raised including convenience, presentation and the need to allow a more unified theory model. These are discussed in this article’s “responses to just criticism” (Shostakovich, 1937). It continues the debate on triple and higher-order helices by summarising and responding to the points made by those commentators. What may be the status of triple and/or higher-order helices?

Triple, Quadruple and N-Tuple Helices: The RIS3 and EDP of a Higher-Order Policy Model

Abstract In the past decade there have been a series of articles on the status of Triple, Quadruple and N-Tuple Helices. In responding to the most recent of these from Leydesdorff and Lawson Smith (2022), this article examines the respective status of the Triple and Quadruple Helix as the scientific basis of the Research and Innovation Strategies related to Smart Specialisation (RIS3) and as the foundation of the Entrepreneurial Discovery Process (EDP). In conducting this examination, the article draws attention to the strengths of the Triple Helix Model, the communication overlay, fourth selection environment and associated ecology of the meta-stabilisation it posits not as the Quadruple Helix, but N-Tuple helices of a higher-order policy model. That policy model which stands high in terms of the status it commands as a regime governing the transition to a next-order system. To a next-order system whose governing regime commands this heightened status as the model policy for nation-states to adopt in sustaining the economic growth of regions.

Measuring Helix Interactions in the Context of Economic Development and Public Policies: From Triple to Quadruple and N-Tuple Helix vs. N-Tuple and Quadruple Helix to Triads

Abstract Quadruple collaboration has risen rapidly in place of the traditional triple helix model of institutional collaboration between universities, governments, and companies. Loet Leydesdorff and Helen Lawton Smith (2022) approach this challenge by aiming to resolve the issue of evaluating and analyzing various quadruple and n-tuple helices. This article seeks to recognize the increasing complexity of new and developing issues in quadruple and n-tuple helices as a response to their research. Higher order helices raise a number of important scientific difficulties, including conceptual and practical issues. The goal of this contribution is to highlight some of the major challenges involved with researching multiple helixes in terms of knowledge innovation, as well as to offer some alternative areas for future research on n-tuple helices measurement.

Triple, Quadruple, and Higher-Order Helices: Historical Phenomena and (Neo-)Evolutionary Models

Abstract Carayannis and Campbell (2009; 2010) have argued for using quadruple and quintuple helices as models encompassing and generalizing triple-helix dynamics. In the meantime, quadruple and quintuple helices have been adopted by the European Committee for the Regions and the European Commission as metaphors for further strategy development such as in EU-programs in Smart Specialization, Plan S, Open Innovation 2.0, etc. Here we argue that the transition from a double helix to a triple helix can change the dynamic from a trajectory to a regime. However, next-order transitions (e.g., to quadruple, quintuple, or n-tuple helices) can be decomposed and recombined into interacting Triple Helices. For example, in the case of four helices A, B, C, and D, one can distinguish ABC, ABD, ACD, and BCD; each triplet can generate synergy. The triple-helix synergy indicator can thus be elaborated for more than three dimensions. However, whether innovation systems are national, regional, sectorial, triple-helix, quadruple-helix, etc., can inform policies with evidence if one proceeds to measurement. A variety of perspectives can be used to interpret the data. Software for testing perspectives will be introduced.

Have Quadruple and Quintuple Helices Emerged? Metaphors, Project Titles, and Empirical Research

Have Quadruple and Quintuple Helices Emerged? Metaphors, Project Titles, and Empirical Research

Electronic Circular Dichroism Spectra of DNA Quadruple Helices Studied by Molecular Dynamics Simulations and Excitonic Calculations including Charge Transfer States.

We here investigate the Electronic Circular Dichroism (ECD) Spectra of two representative Guanine-rich sequences folded in a Quadruple helix (GQ), by using a recently developed fragment diabatisation based excitonic model (FrDEx). FrDEx can include charge transfer (CT) excited states and consider the effect of the surrounding monomers on the local excitations (LEs). When applied to different structures generated by molecular dynamics simulations on a fragment of the human telomeric sequence (Tel21/22), FrDEx provides spectra fully consistent with the experimental one and in good agreement with that provided by quantum mechanical (QM) method used for its parametrization, i.e., TD-M05-2X. We show that the ECD spectrum is moderately sensitive to the conformation adopted by the bases of the loops and more significantly to the thermal fluctuations of the Guanine tetrads. In particular, we show how changes in the overlap of the tetrads modulate the intensity of the ECD signal. We illustrate how this correlates with changes in the character of the excitonic states at the bottom of the and bands, with larger LE and CT involvement of bases that are more closely stacked. As an additional test, we utilised FrDEx to compute the ECD spectrum of the monomeric and dimeric forms of a GQ forming sequence T30695 (5TGGGTGGGTGGGTGGG3), i.e., a system containing up to 24 Guanine bases, and demonstrated the satisfactory reproduction of the experimental and QM reference results. This study provides new insights on the effects modulating the ECD spectra of GQs and, more generally, further validates FrDEx as an effective tool to predict and assign the spectra of closely stacked multichromophore systems.

Helix Trilogy: the Triple, Quadruple, and Quintuple Innovation Helices from a Theory, Policy, and Practice Set of Perspectives

Helix Trilogy: the Triple, Quadruple, and Quintuple Innovation Helices from a Theory, Policy, and Practice Set of Perspectives

Triple, Quadruple, and Higher-Order Helices: Historical Phenomena and (Neo-)Evolutionary Models

Carayannis and Campbell (e.g., 2009; 2010) have argued for using Quadruple and Quintuple Helices as models encompassing and generalizing Triple-Helix dynamics. In the meantime, Quadruple and Quintuple Helices have been adopted by the European Committee for the Regions and the European Commission as metaphors for further strategy development such as in EU-programs in Smart Specialization, Plan S, Open Innovation 2.0, etc. Here we argue that the transition from a Double Helix to a Triple Helix can change the dynamic from a trajectory to a regime. However, next-order transitions (e.g., to Quadruple, Quintuple, or N-tuple Helices) can be decomposed and recombined into interacting Triple Helices. For example, in the case of four helices A, B, C, and D, one can distinguish ABC, ABD, ACD, and BCD; each triplet can generate synergy. The Triple-Helix synergy indicator can thus be elaborated for more than three dimensions. However, whether innovation systems are national, regional, sectorial, Triple-Helix, Quadruple-Helix, etc., can inform policies with evidence when one proceeds to measurement. A variety of perspectives can be used to interpret the data. Software for testing perspectives will be introduced.

Excitonic Model for Strongly Coupled Multichromophoric Systems: The Electronic Circular Dichroism Spectra of Guanine Quadruplexes as Test Cases.

We here propose a general and flexible approach, based on fragment diabatization, which incorporates charge transfer states and significantly increases the reliability of excitonic Hamiltonians for systems where the chromophores are very close. This model (FrDEx) is used to compute the electronic circular dichroism and absorption spectra of two prototype guanine-rich DNA sequences folded in quadruple helices (GQs), i.e., a fragment of the human telomeric sequence (Tel21, antiparallel), and (TGGGGT)4 (TG4T, parallel). Calculations on different subsets of Tel21 and TG4T, from dimers to tetramers, show that FrDEx provides spectra close to the reference full quantum mechanical (QM) ones (obtained with time-dependent density functional theory), with significant improvements with respect to "standard" excitonic Hamiltonians. Furthermore, these tests enable the most cost-effective procedure for the whole GQ to be determined. FrDEx spectra of Tel21 and TG4T are also in good agreement with the QM and experimental ones and give access to interesting insights into the chemical-physical effects modulating the spectral signals. FrDEx could be profitably used to investigate many other biological and nanotechnological materials, from DNA to (opto)electronic polymers.

Unraveling the B to A Conformational Transition in Duplex DNA at Single Base Pair Resolution

DNA shows conformational heterogeneity and the interest in non‐canonical DNA conformations is increasing as these conformers are found to be involved in many important biological process. Although triple helices, quadruple helices and supercoils are the most studied structures, the conformational transition of the standard B‐form DNA helix to A‐form DNA was the first observed one. The transition of B‐DNA double helix to A‐form is essential for biological functions as recognized by the presence of A‐form DNA in many protein‐DNA complexes. Even though it is known that the B to A conformational transition occurs, the specifics like where in the DNA it originates, how it propagates, and the detailed step‐by‐step mechanism involved is still unknown. By using site specifically positioned fluorescent oligonucleotides, we explored the local and global conformational changes in this transition. Our results showed that by using 2‐Aminopurine (2‐AP), a fluorescent analogue of Adenine, we could monitor the local and global conformational change simultaneously. As a next step our aim is to introduce spermine or spermidine to the system at different ethanol percentages and monitor the spectral changes at various intervals of this transition. This will help us to understand the fundamentals of the long known B to A DNA conformational transition.

Anion-Coordination-Driven Assembly of Chiral Quadruple and Single Helices Controlled by Countercations

Enantiopure helical assemblies were constructed by chiral C2-symmetric bis-bis(urea) ligands (LS/R) with phosphate or hydrogen phosphate anion, which is dictated by the countercation. In the presen...

Responsible innovation through conscious contestation at the interface of agricultural science, policy, and civil society

This research examines a series of case studies from the agricultural sector to illustrate how various models of innovation embrace value proposition. A conscious value contestation at the interface of science, policy and civil society requires transformations in the triple-helix model of university-government-industry collaboration, because reiterations in the triple-helix model of innovation, such as quadruple, quintuple and higher helices, do not necessarily address civil society concerns for human values and science ethics. This research develops and tests a matrix model of university-government-industry-civil society collaboration, which involves the co-creation of inclusive and transformational spaces for value proposition. Findings suggest that the matrix model of innovation institutionalises citizen science as it serves as a moral heuristic to make seemingly apolitical science responsive to essentially contested societal values.

DNA Quadruple Helices in Nanotechnology.

DNA has played an early and powerful role in the development of bottom-up nanotechnologies, not least because of DNA's precise, predictable, and controllable properties of assembly on the nanometer scale. Watson-Crick complementarity has been used to build complex 2D and 3D architectures and design a number of nanometer-scale systems for molecular computing, transport, motors, and biosensing applications. Most of such devices are built with classical B-DNA helices and involve classical A-T/U and G-C base pairs. However, in addition to the above components underlying the iconic double helix, a number of alternative pairing schemes of nucleobases are known. This review focuses on two of these noncanonical classes of DNA helices: G-quadruplexes and the i-motif. The unique properties of these two classes of DNA helix have been utilized toward some remarkable constructions and applications: G-wires; nanostructures such as DNA origami; reconfigurable structures and nanodevices; the formation and utilization of hemin-utilizing DNAzymes, capable of generating varied outputs from biosensing nanostructures; composite nanostructures made up of DNA as well as inorganic materials; and the construction of nanocarriers that show promise for the therapeutics of diseases.

Halogen Bonding Directed Supramolecular Quadruple and Double Helices from Hydrogen-Bonded Arylamide Foldamers.

Halogen bonding has been used to glue together hydrogen-bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF2 I or fluorinated iodobenzene group at the other end, engage in head-to-tail N⋅⋅⋅I halogen bonds to form one-component supramolecular P and M helices, which stack to afford supramolecular double-stranded helices. One of the double helices can dimerize to form a G-quadruplex-like supramolecular quadruple helix. Another symmetric compound, which bears a pyridine at each end, binds to ICF2 CF2 I through N⋅⋅⋅I halogen bonds to form two-component supramolecular P and M helices, with one turn consisting of four (2+2) molecules. Half of the pyridine-bearing molecules in two P helices and two M helices stack alternatingly to form another supramolecular quadruple helix. Another half of the pyridine-bearing molecules in such quadruple helices stack alternatingly with counterparts from neighboring quadruple helices, leading to unique quadruple helical arrays in two-dimensional space.

Halogen Bonding Directed Supramolecular Quadruple and Double Helices from Hydrogen‐Bonded Arylamide Foldamers

AbstractHalogen bonding has been used to glue together hydrogen‐bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF2I or fluorinated iodobenzene group at the other end, engage in head‐to‐tail N⋅⋅⋅I halogen bonds to form one‐component supramolecular P and M helices, which stack to afford supramolecular double‐stranded helices. One of the double helices can dimerize to form a G‐quadruplex‐like supramolecular quadruple helix. Another symmetric compound, which bears a pyridine at each end, binds to ICF2CF2I through N⋅⋅⋅I halogen bonds to form two‐component supramolecular P and M helices, with one turn consisting of four (2+2) molecules. Half of the pyridine‐bearing molecules in two P helices and two M helices stack alternatingly to form another supramolecular quadruple helix. Another half of the pyridine‐bearing molecules in such quadruple helices stack alternatingly with counterparts from neighboring quadruple helices, leading to unique quadruple helical arrays in two‐dimensional space.

Channeling through Two Stacked Guanine Quartets of One and Two Alkali Cations in the Li+, Na+, K+, and Rb+ Series. Assessment of the Accuracy of the SIBFA Anisotropic Polarizable Molecular Mechanics Potential.

Stacking of guanine quartets (GQs) can trigger the formation of DNA or RNA quadruple helices, which play numerous biochemical roles. The GQs are stabilized by alkali cations, mainly K+ and Na+, which can reside in, or channel through, the central axis of the GQ stems. Further, ion conduction through GQ wires can be leveraged for nanochemistry applications. G-quadruplex systems have been extensively studied by classical molecular dynamics (MD) simulations using pair-additive force fields or by quantum-chemical (QC) calculations. However, the non-polarizable force fields are very approximate, while QC calculations lack the necessary sampling. Thus, ultimate description of GQ systems would require long-enough simulations using advanced polarizable molecular mechanics (MM). However, to perform such calculations, it is first mandatory to evaluate the method's accuracy using benchmark QC. We report such an evaluation for SIBFA polarizable MM, bearing on the channeling (movement) of an alkali cation (Li+, Na+, K+, or Rb+) along the axis of two stacked G quartets interacting with either one or two ions. The QC energy profiles display markedly different features depending upon the cation but can be retrieved in the majority of cases by the SIBFA profiles. An appropriate balance of first-order (electrostatic and short-range repulsion) and second-order (polarization, charge-transfer, and dispersion) contributions within ΔE is mandatory. With two cations in the channel, the relative weights of the second-order contributions increase steadily upon increasing the ion size. In the G8 complexes with two K+ or two Rb+ cations, the sum of polarization and charge-transfer exceeds the first order terms for all ion positions.

Best packing of identical helices

In this paper we prove the unique existence of a ropelength-minimizing conformation of the θ-spun double helix in a mathematically rigorous way, and find the minimal ropelength where t is the unique solution in of the equation . Using this result, the pitch angles of the standard, triple and quadruple helices are around , and , respectively, which are almost identical with the approximated pitch angles of the zero-twist structures previously known by Olsen and Bohr. We also find the ropelength of the standard N-helix.