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Search Results (232)

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23 pages, 3365 KB  
Article
From Discipline to Improvisation: A Practice-Based Model for Training Creativity
by Yuli Liang, Peter Walgenbach and Stefan R. Schweinberger
Educ. Sci. 2026, 16(8), 1311; https://doi.org/10.3390/educsci16081311 - 17 Aug 2026
Viewed by 317
Abstract
For a long time, research on creativity has focused more on cognitive aspects (“minds”) rather than the production side (“actions”). This paper examines the creative practice as a subjective experience, using researcher introspection as a qualitative methodology. Through in-depth reflection on the creative [...] Read more.
For a long time, research on creativity has focused more on cognitive aspects (“minds”) rather than the production side (“actions”). This paper examines the creative practice as a subjective experience, using researcher introspection as a qualitative methodology. Through in-depth reflection on the creative development of an Ikebana artist, this study captures the complexity of creative practice, and offers detailed insights into its embodied and procedural dimensions, including experimentation and flow. Drawing on the theory of deliberate practice, the study challenges the notion that creativity is purely spontaneous and demonstrates how improvisation emerges through disciplined practice and deliberate experimentation. We propose a three-stage, practice-based model for training creativity: mastering fundamentals, exploring variations, and ultimately breaking free from established forms. Full article
(This article belongs to the Section Education and Psychology)
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37 pages, 1609 KB  
Article
A Non-Equilibrium Thermodynamic Framework for Sequential Symmetry Breaking in Driven Complex Fluids
by Antonio F. Miguel, Vinicius R. Pepe and Luiz A. O. Rocha
Entropy 2026, 28(8), 910; https://doi.org/10.3390/e28080910 - 13 Aug 2026
Viewed by 194
Abstract
The spontaneous emergence of macroscopic order in driven, far-from-equilibrium complex fluids lacks a generalized framework capable of bridging continuous and discrete symmetry-breaking transitions. In this study, we propose a non-equilibrium phenomenological framework that synthesizes irreversible thermodynamics, coupled Landau–de Gennes potential expansions, and active [...] Read more.
The spontaneous emergence of macroscopic order in driven, far-from-equilibrium complex fluids lacks a generalized framework capable of bridging continuous and discrete symmetry-breaking transitions. In this study, we propose a non-equilibrium phenomenological framework that synthesizes irreversible thermodynamics, coupled Landau–de Gennes potential expansions, and active hydrodynamics. The formulation employs a single tensorial order parameter, a nonlinear state-dependent jamming mobility closure, and a generalized set of dimensionless groups to map the non-equilibrium phase space. The model predicts a sequential symmetry-breaking cascade and reproduces the emergence of polar heliconical smectic and antiferroelectric phases in driven liquid crystals, as well as the transition from isotropic active gases to macroscopic fluid flocks and active Wigner crystals in purely repulsive Janus colloids. Across these systems, a dimensionless active torque number acts as the principal bifurcation parameter, suggesting that their macroscopic structural transitions are governed by a common balance between thermodynamic and kinematic effects rather than by the details of their microscopic interactions. Full article
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30 pages, 7655 KB  
Review
Extracting Phase Structure and Stability of the Magnetic Dual Chiral Density Wave from a Ginzburg–Landau Expansion
by William Gyory
Universe 2026, 12(7), 208; https://doi.org/10.3390/universe12070208 - 11 Jul 2026
Viewed by 387
Abstract
We review some recent findings on thermal properties of the magnetic dual chiral density wave (MDCDW) condensate in the Nambu–Jona-Lasinio (NJL) model of dense quark matter, as well as a convenient method for investigating this phase with a high-order Ginzburg–Landau (GL) expansion. We [...] Read more.
We review some recent findings on thermal properties of the magnetic dual chiral density wave (MDCDW) condensate in the Nambu–Jona-Lasinio (NJL) model of dense quark matter, as well as a convenient method for investigating this phase with a high-order Ginzburg–Landau (GL) expansion. We show how a recently discovered formula for the GL coefficients can be used to compute key physical properties of the condensate, such as its ground state order parameters and critical temperature in the mean-field approximation and its stability against thermal phonon fluctuations. We find that magnetic fields of order 1018 G significantly increase the condensate magnitude and critical temperature, eventually making the condensate favored up to temperatures a few times 10 MeV over the entire range of densities in the model. At much smaller fields, the condensate is still preferred and thermally stable over a range of densities relevant to cold neutron stars. We emphasize how the topological features of MDCDW are encoded in certain terms of the GL expansion, which can be used to show that the preceding effects have a topological origin. Finally, we present a new result on the convergence properties of the GL expansion, proving that it converges when |m|+|b|<μ2+(πT)2, where m and b are order parameters proportional to the condensate magnitude and spatial modulation, respectively. This condition holds over a large region of parameter space, including the region of interest for neutron star applications. Full article
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16 pages, 2605 KB  
Article
Study on Pore Structure of Shale and Fluid Distribution Patterns of Surfactant-Enhanced Spontaneous Imbibition
by Jinmei Bai, Jiale Ren, Xianzhuang Li, Hui Xu, Xiangji Dou and Yanfeng He
Appl. Sci. 2026, 16(12), 6230; https://doi.org/10.3390/app16126230 - 20 Jun 2026
Viewed by 336
Abstract
Spontaneous imbibition modified by surfactants is a key technology for enhancing shale oil recovery. Currently, relevant studies mainly concentrate on marine shale worldwide, while the pore–fluid coupling characteristics of widely distributed medium-TOC terrestrial shale remain poorly understood. Against this background, this paper takes [...] Read more.
Spontaneous imbibition modified by surfactants is a key technology for enhancing shale oil recovery. Currently, relevant studies mainly concentrate on marine shale worldwide, while the pore–fluid coupling characteristics of widely distributed medium-TOC terrestrial shale remain poorly understood. Against this background, this paper takes typical Paleogene terrestrial shale as the research object and integrates N2/CO2 adsorption and NMR T2 spectroscopy to jointly characterize multiscale pore structures and dynamic fluid evolution during imbibition. The results show that the shale is dominated by mesopores in terms of pore volume, while micropores provide most of the specific surface area. The zwitterionic surfactant HPSB can greatly reduce oil–water interfacial tension and alter rock wettability, thereby breaking the high capillary resistance of micropores. During imbibition, water invades macropores first, followed by mesopores and micropores, and the entire process exhibits remarkable nonlinear dynamics controlled by multiscale pores. The 0.15% HPSB solution shows the best effect on activating micropores. This study innovatively quantifies the influence of surfactant concentration on fluid migration across different pore scales and reveals the internal mechanism of staged imbibition and micropore lag activation in terrestrial shale. It not only complements the global research system of shale imbibition theory but also offers practical guidance for the optimization of fracturing fluid systems in mesopore-dominated shale oil reservoirs. Full article
(This article belongs to the Section Energy Science and Technology)
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19 pages, 20790 KB  
Article
Coal Spontaneous Oxidation Mechanism of Low-Molecular Compounds: Pentanol
by Tianyi Yang, Xiaobo Wang, Wenhao Deng, Sichen Liu, Hanzhong Deng and Yafei Shan
Fire 2026, 9(6), 253; https://doi.org/10.3390/fire9060253 - 13 Jun 2026
Viewed by 675
Abstract
Coal spontaneous combustion (CSC) remains a major hazard in coal mining. Research on CSC has largely focused on macromolecular structures, while the behavior of low-molecular-weight compounds remains unclear. Using B3LYP/6-311G density functional theory, this study systematically reveals thirteen microscopic reaction pathways, active sites, [...] Read more.
Coal spontaneous combustion (CSC) remains a major hazard in coal mining. Research on CSC has largely focused on macromolecular structures, while the behavior of low-molecular-weight compounds remains unclear. Using B3LYP/6-311G density functional theory, this study systematically reveals thirteen microscopic reaction pathways, active sites, and the energy barrier order of pentanol during coal spontaneous combustion. The oxidation proceeds via thirteen multi-step pathways involving bond breaking and formation, with the dominant reaction being oxygen attack on the -CH2OH group to produce pentanal (CH3CH2CH2CH2CHO) and water as the main products. The priority order of thirteen reaction pathways between pentanol and oxygen was established as: Path 6 > Path 3 > Path 8 > Path 5 > Path 4 > Path 1 > Path 11 > Path 10 > Path 9 > Path 12 > Path 7 > Path 2. The results reveal the multi-step bond-breaking and formation mechanism at the molecular level, providing a fundamental theoretical framework for understanding the radical chain oxidation mechanism of low molecular weight compounds in CSC. Full article
(This article belongs to the Special Issue Fire Risk Management and Emergency Prevention)
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36 pages, 1329 KB  
Article
Chiral Quark Soliton Model and Nucleon Parton Distribution Functions
by Masashi Wakamatsu
Symmetry 2026, 18(6), 892; https://doi.org/10.3390/sym18060892 - 24 May 2026
Viewed by 289
Abstract
The chiral quark soliton model (CQSM) is an effective quark model of baryons maximally taking account of the most important feature of low-energy QCD, i.e., the spontaneous chiral symmetry breaking of the QCD vacuum and the associated appearance of Nambu–Goldstone pions. It shares [...] Read more.
The chiral quark soliton model (CQSM) is an effective quark model of baryons maximally taking account of the most important feature of low-energy QCD, i.e., the spontaneous chiral symmetry breaking of the QCD vacuum and the associated appearance of Nambu–Goldstone pions. It shares many common features with the famous Skyrme model in that the baryons are viewed as rotating hedgehog objects in both models. Despite many similarities, it turned out that the CQSM can give more realistic predictions on most baryon observables. Above all, a decisive advantage of the CQSM over the Skyrme-like models is that it can handle non-local quark–quark correlations in baryons, which is absolutely impossible within the framework of effective meson theories. This feature is decisively important for making theoretical predictions on the quark distribution functions inside the nucleon, which are defined as nucleon matrix elements of bilinear quark operators with light-cone separation. In the present paper, we try to elucidate why and how the CQSM can give successful predictions for a variety of types of nucleon quark distribution functions, especially for the flavor asymmetry of the unpolarized and longitudinally polarized sea-quark (anti-quark) distribution functions in the nucleon. Full article
(This article belongs to the Special Issue Chiral Quark Models and Their Applications)
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25 pages, 672 KB  
Article
Induced-Gravity Palatini-like Higgs Inflation in Supergravity Confronts ACT DR6
by Constantinos Pallis
Astronomy 2026, 5(2), 9; https://doi.org/10.3390/astronomy5020009 - 22 May 2026
Cited by 3 | Viewed by 364
Abstract
We formulate within Supergravity a model of induced-gravity inflation, excellently consistent with ACT DR6, inspired by the Palatini gravity. The inflaton belongs in the decomposition of a conjugate pair of Higgs superfields which lead to the spontaneous breaking of a [...] Read more.
We formulate within Supergravity a model of induced-gravity inflation, excellently consistent with ACT DR6, inspired by the Palatini gravity. The inflaton belongs in the decomposition of a conjugate pair of Higgs superfields which lead to the spontaneous breaking of a U(1)BL symmetry at a scale close to the range (0.145–8.35) × 1016 GeV. The inflaton field is canonically normalized thanks to one real and shift-symmetric contribution into the Kähler potential. It also includes two separate holomorphic and antiholomorphic logarithmic terms, the argument of which can be interpreted as the coupling of the inflaton to the Ricci scalar. The attainment of inflation allows for subplanckian inflaton values and energy scales below the cut-off scale of the corresponding effective theory. Embedding the model in a BL extension of the MSSM we show how the μ parameter can be generated and non-thermal leptogenesis can be successfully realized. An outcome of our scheme is split SUSY with gravitino mass in the range (40–60) PeV, which is consistent with the results of LHC on the Higgs boson mass. Full article
(This article belongs to the Special Issue Current Trends in Cosmology)
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14 pages, 566 KB  
Article
Dark NLO Correction to Dark Photon Production at Lepton Colliders
by Jianming Zheng, Yi Li, Yusi Pan and Mengchao Zhang
Universe 2026, 12(6), 153; https://doi.org/10.3390/universe12060153 - 22 May 2026
Viewed by 347
Abstract
In this work, we calculate the inclusive cross-section for the single dark photon production process in an electron–positron collider up to next-to-leading order (NLO). The dark photon studied in this work is embedded in a more complete dark Abelian Higgs model charged under [...] Read more.
In this work, we calculate the inclusive cross-section for the single dark photon production process in an electron–positron collider up to next-to-leading order (NLO). The dark photon studied in this work is embedded in a more complete dark Abelian Higgs model charged under a spontaneously broken U(1) gauge symmetry. The breaking of U(1) generates the mass of the dark photon. The inclusive cross-section contains σ(e+eγA) and σ(e+eγAs), with A/s being the dark photon/the dark Higgs, respectively. To remove the infrared (IR) divergence that appears at the high energy limit, virtual correction from the dark sector, which is the self-energy of dark photon, is also included. The cancellation of the IR divergences between the real correction and virtual correction makes the final NLO cross-section IR-safe. The phenomenological effect of this NLO correction is also briefly discussed. Full article
(This article belongs to the Special Issue Search for New Physics Through Combined Approaches)
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22 pages, 328 KB  
Article
Spontaneous BRST Symmetry Breaking in Infrared QCD
by Angelo Raffaele Fazio and Adam Smetana
Universe 2026, 12(5), 138; https://doi.org/10.3390/universe12050138 - 7 May 2026
Viewed by 412
Abstract
We present a novel proposal for the effective Lagrangian of the low-energy Yang–Mills quantum field theory. The proposed effective Lagrangian exhibits the spontaneous BRST symmetry breaking. We build on the Fujikawa model that we couple to the Yang–Mills elementary field sector, motivated by [...] Read more.
We present a novel proposal for the effective Lagrangian of the low-energy Yang–Mills quantum field theory. The proposed effective Lagrangian exhibits the spontaneous BRST symmetry breaking. We build on the Fujikawa model that we couple to the Yang–Mills elementary field sector, motivated by the analogy with Chiral Quark Model. We interpret the Fujikawa fields as effective fields, composites of the elementary gluon and ghost fields. In order to justify the existence of two massless Nambu–Goldstone modes among the Fujikawa fields, we require not only the BRST but also the anti-BRST invariance of the effective Lagrangian, with both being spontaneously broken. The most striking consequence of that is the emergence of the effective gluon and ghost masses. We reproduce the Curci–Ferrari model as a special case of our effective model upon the spontaneous BRST symmetry breaking. In order to reproduce also the non-nilpotent modified-BRST symmetry, characteristic for the Curci–Ferrari model, we modify our effective Lagrangian to be invariant with respect to the extended-BRST symmetry, which mixes the elementary and Fujikawa field sectors, and which is nilpotent. The Curci–Ferrari model is reproduced by the elementary field sector of the resulting Lagrangian. The remaining Fujikawa-field-dependent terms guarantee the underlying nilpotent extended-BRST symmetry, which is now hidden in the sense of the spontaneous symmetry breaking. Full article
(This article belongs to the Section Field Theory)
24 pages, 1499 KB  
Article
Emergence and Stabilization of Hemispheric Specialization Under Symmetric Developmental Conditions: A Minimal Evolutionary Model
by Nobuchika Yamaki and Tenna Churiki
Symmetry 2026, 18(5), 783; https://doi.org/10.3390/sym18050783 - 2 May 2026
Viewed by 809
Abstract
Hemispheric specialization is a widespread feature of vertebrate nervous systems, but the minimal conditions under which bilateral systems differentiate, acquire polarity, and retain asymmetric states remain unclear. Here, we examined these issues using a minimal evolutionary model with two initially equivalent processing channels. [...] Read more.
Hemispheric specialization is a widespread feature of vertebrate nervous systems, but the minimal conditions under which bilateral systems differentiate, acquire polarity, and retain asymmetric states remain unclear. Here, we examined these issues using a minimal evolutionary model with two initially equivalent processing channels. Each channel evolved a spatial integration width while receiving the same input, and fitness rewarded the magnitude of a bilateral mismatch-separation signal rather than explicit anomaly localization. Under exact developmental symmetry, 40 lineages evolved robust left–right differences in integration width without significant directional fixation (median |Δa| = 2.511; 22 right-wider, 18 left-wider). Weak developmental gain asymmetry biased polarity selection in a graded manner, shifting outcomes toward right-wider or left-wider solutions depending on bias direction. Forced-symmetry, shared-parameter, and single-channel controls showed that high performance depended on allowing differentiated bilateral processing. After biased solutions were reseeded under restored symmetry, differentiation was retained and amplified (median |Δa| > 6.6), consistent with history-dependent persistence within the sampled fitness landscape. Structured backgrounds increased differentiation magnitude but imposed greater decision-time costs. These results distinguish differentiation, polarity bias, and persistence as separable components of minimal hemispheric specialization. Full article
(This article belongs to the Special Issue Symmetry and Asymmetry in Computational Biology)
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17 pages, 2479 KB  
Article
Reproductive Biology and Germination Ecology of Phytolacca acinosa in Its Secondary Range
by Aleksandra V. Stogova, Aleksandr A. Ivanovskii, Ekaterina V. Tkacheva, Marianna A. Zueva, Aleksandr K. Mamontov, Yulya. K. Vinogradova and Olga V. Shelepova
Plants 2026, 15(9), 1362; https://doi.org/10.3390/plants15091362 - 29 Apr 2026
Viewed by 394
Abstract
Phytolacca acinosa Roxb., a perennial herb native to East Asia, is increasingly naturalizing in Europe, yet its reproductive ecology in the secondary range remains poorly understood. This study evaluated seed productivity across central and edge populations in the secondary range, fruit and seed [...] Read more.
Phytolacca acinosa Roxb., a perennial herb native to East Asia, is increasingly naturalizing in Europe, yet its reproductive ecology in the secondary range remains poorly understood. This study evaluated seed productivity across central and edge populations in the secondary range, fruit and seed morphometrics, and germination responses to cold storage, acid scarification (simulating bird endozoochory), and light exposure. Fruit production per raceme was influenced by an interaction between insolation and range position: reduced insolation increased fruit set in central populations but decreased it at the range edge. Raceme number per shoot was lower in spontaneous plants compared to cultivated ones. Fresh seeds exhibited strong dormancy with no germination without scarification. Acid scarification significantly enhanced germination, particularly with light exposure, reaching up to 55%. Cold storage did not increase germination percentage but accelerated germination of scarified seeds under light, reducing median germination time from 24 to 21 days. Compared to the congeneric P. americana, P. acinosa shows more stringent dormancy requirements. We conclude that P. acinosa retains deep seed dormancy in its secondary range and relies on bird-mediated endozoochory for both dispersal and dormancy release. At the northern range edge, reduced plant vigor and lower raceme numbers are partially offset by increased flower production per raceme, though fruit set remains constrained. The species does not exhibit the simplified germination requirements often associated with successful invaders; instead, its invasion success appears driven by a bet-hedging strategy combining persistent seed banks with specific dormancy-breaking cues. Full article
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17 pages, 450 KB  
Review
A Solution of the Scalar Nonet Mass Puzzle
by Mihail Chizhov, Emanuil Chizhov, Daniela Kirilova and Momchil Naydenov
Particles 2026, 9(2), 44; https://doi.org/10.3390/particles9020044 - 23 Apr 2026
Viewed by 458
Abstract
We present a short review dedicated to low-lying meson states. We present all meson nonets, which consist from up, down and strange light quarks. We consider the scalar nonet as a basic nonet. We work in the framework of the massless Nambu–Jona-Lasinio [...] Read more.
We present a short review dedicated to low-lying meson states. We present all meson nonets, which consist from up, down and strange light quarks. We consider the scalar nonet as a basic nonet. We work in the framework of the massless Nambu–Jona-Lasinio UR(3)×UL(3) quark model. The collective meson states are described through initially bare quark–antiquark pairs, whose condensates lead simultaneously to spontaneous breaking of the chiral and the flavour symmetry. After quantisation and the spontaneous breaking of the chiral symmetry, when quarks obtain constituent nonzero masses, they become dressed. We present an explanation of the inverse mass hierarchy of the low-lying nonet of the scalar mesons. The proposed explanation is based on symmetry principles. It is shown that, due to the flavour symmetry breaking, two isodoublets of K0*(700) mesons play the role of Goldstone bosons. It is also proven that there exists a solution with almost degenerate masses of the a0(980) and f0(980) mesons and a zero mass of the f0(500) meson. Short description of the physical properties of other meson nonets is provided. In particular unique mass relations among the different nonets, which are experimentally confirmed, are presented. Full article
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28 pages, 794 KB  
Article
Emergent Higgs Field and the Schwarzschild Black Hole
by Dragana Pilipović
Particles 2026, 9(2), 37; https://doi.org/10.3390/particles9020037 - 3 Apr 2026
Viewed by 2143
Abstract
The derivations presented in this paper suggest an intimate relationship between geometry and the electroweak sector at the Planck scale. A Lorentz-invariant maximally symmetric stochastically perturbed spacetime transformed to spherical coordinates reveals an emergent Schwarzschild metric, entirely a statistical structure of stochastic spacetime. [...] Read more.
The derivations presented in this paper suggest an intimate relationship between geometry and the electroweak sector at the Planck scale. A Lorentz-invariant maximally symmetric stochastically perturbed spacetime transformed to spherical coordinates reveals an emergent Schwarzschild metric, entirely a statistical structure of stochastic spacetime. Similarly, the transition from a maximally symmetric universe with a complex SU(2) scalar doublet ϕ, comprising four independent real scalar fields with a zero vacuum expectation value (VEV), to spherical coordinates at the Planck scale reveals the spontaneously broken electroweak (EW) sector. Working in the unitarity gauge, the resulting EW potential can be simultaneously mapped in space at the Planck scale and across the EW sector. In space, the resulting EW potential includes a deep well within the Schwarzschild sphere and a shallow well just outside corresponding to an accretion disk. The same potential mapped in the EW space provides an entire family of possible sombrero hat potentials with fourth-order coupling specific to a point in space. At the minimum points of the potential in space, inside the Schwarzschild sphere and at the accretion disk, the λ corresponding to the Standard Model (SM) fourth-order coupling is instead derived as λ5. The factor of 15 is a simple consequence of the conservation of the EW VEV and the fact that the SM formulation of the EW potential does not account for situations where the perturbations in ϕ dominate. A more general formulation of the EW potential restores the SM quartic coupling and preserves λ in space. An emergent Higgs field inside the Schwarzschild black hole is found to directly relate to the stochastic spacetime fields normalized by the Schwarzschild radius. The corresponding Higgs vacuum has both a ground and excited state and the possibility of both positive and negative vacuum entropy. Finally, the scalar-field VEV degeneracy in EW space of the metastable Higgs vacuum appears instead differentiated in space with possible probability, tunneling, and entropy implications. Full article
(This article belongs to the Section Phenomenology and Physics Beyond the Standard Model)
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49 pages, 676 KB  
Article
Two-Measure Electroweak Standard Model and Its Realization During Cosmological Evolution
by Alexander B. Kaganovich
Symmetry 2026, 18(3), 508; https://doi.org/10.3390/sym18030508 - 16 Mar 2026
Viewed by 376
Abstract
The possibility of realizing Higgs inflation in a model with a small non-minimal coupling constant, which was demonstrated recently, provides grounds for further development of the model. Incorporating the electroweak SM into the Two-Measure theory (TMT) in a way that fully accounts for [...] Read more.
The possibility of realizing Higgs inflation in a model with a small non-minimal coupling constant, which was demonstrated recently, provides grounds for further development of the model. Incorporating the electroweak SM into the Two-Measure theory (TMT) in a way that fully accounts for the TMT structure leads to a theory we call the Two-Measure Standard Model (TMSM). The TMSM is realized in the context of cosmology as a set of cosmologically modified copies of the Glashow–Weinberg–Salam (GWS) theory, such that each of the copies exists as a local quantum field theory defined on the classical cosmological background at the appropriate stage of its evolution. This basic idea is studied in detail for two stages of the cosmological background evolution: for slow-roll inflation and for the stage of approaching the vacuum. Mainly due to the presence of the ratio of two volume measures in all equations of motion, all TMSM coupling constants turn into a kind of “running” (classical) TMT-effective parameters. During the evolution of the cosmological background, changing these parameters yields new results: (1) the classical “running” TMT-effective Higgs self-coupling parameter increases from λ1011 (which provides Higgs inflation consistent with the Planck CMB data at ξ=16) to λ0.1 at the stage close to the vacuum; (2) the mass term in the TMT-effective Higgs potential changes sign from positive to negative, which provides SSB in the standard way of GWS theory; (3) the classical “running” parameters of the gauge and Yukawa couplings change by several orders of magnitude; (4) the GWS theory is reproduced when the Yukawa constant in the original action is chosen to be universal for three generations of fermions. We show that, due to these classical-level results, taking into account quantum corrections in the one-loop approximation preserves the slow-roll inflation regime and does not violate the vacuum stability during inflation. Full article
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14 pages, 2697 KB  
Article
A Computational Model for Nme1Cas9 HNH Activation Driven by Dynamic Interface Engineering at Residues S593 and W596
by Zhenyu Zhou and Lizhe Zhu
Biomolecules 2026, 16(3), 358; https://doi.org/10.3390/biom16030358 - 27 Feb 2026
Viewed by 905
Abstract
Nme1Cas9 is an encouraging genome-editing tool with high fidelity and compactness, but its applications are limited by poor catalytic efficiency compared with SpyCas9. Understanding the dynamic activation mechanism of the HNH nuclease domain is the key to breaking the kinetic bottleneck. Here, we [...] Read more.
Nme1Cas9 is an encouraging genome-editing tool with high fidelity and compactness, but its applications are limited by poor catalytic efficiency compared with SpyCas9. Understanding the dynamic activation mechanism of the HNH nuclease domain is the key to breaking the kinetic bottleneck. Here, we integrated Steered Molecular Dynamics (SMD) with the Traveling-Salesman-based automated Path Searching (TAPS) algorithm to reconstruct the atomic-level activation landscape of the L1-HNH module. The simulations suggest a complex “Lifting-Rearrangement-Sliding” pathway, revealing the critical role of a “Backbone Sliding” conformation; in this step, the HNH domain rotates across the R-loop surface. A thermodynamic analysis using free energy decomposition by MM/PBSA indicates that the intrinsic instability of the wild-type HNH/R-loop interface constitutes the predominant energetic barrier. Hyperactive variants (S593Q/W596K and S593Q/W596R) can overcome this barrier by substantially increasing binding affinity to the R-loop through a “Geometry–Electrostatics Synergism”: S593Q improves interfacial proximity, whereas W596K/R acts as an “Electrostatic Anchor.” The results of unbiased MD simulations demonstrate that strengthened interfacial interactions effectively promote spontaneous conformational drift toward the activated state. This computational study proposes a novel in silico model for “Dynamic Interface Engineering” in which reinforcing transient interfacial contacts during conformational sliding can be an effective strategy in developing high-efficiency CRISPR-Cas effectors. Full article
(This article belongs to the Special Issue Innovative Biomolecular Structure Analysis Techniques)
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