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- Brevini, T, et al.
(författare)
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FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
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Tidskriftsartikel (refereegranskat)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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- Giblin, S. R., et al.
(författare)
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Pauling Entropy, Metastability, and Equilibrium in Dy2Ti2O7 Spin Ice
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:6
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Tidskriftsartikel (refereegranskat)abstract
- Determining the fate of the Pauling entropy in the classical spin ice material Dy2Ti2O7 with respect to the third law of thermodynamics has become an important test case for understanding the existence and stability of ice-rule states in general. The standard model of spin ice-the dipolar spin ice model-predicts an ordering transition at T approximate to 0.15 K, but recent experiments by Pomaranski et al. suggest an entropy recovery over long timescales at temperatures as high as 0.5 K, much too high to be compatible with the theory. Using neutron scattering and specific heat measurements at low temperatures and with long timescales ( 0.35 K/10(6) s and 0.5 K/10(5) s, respectively) on several isotopically enriched samples, we find no evidence of a reduction of ice-rule correlations or spin entropy. High-resolution simulations of the neutron structure factor show that the spin correlations remain well described by the dipolar spin ice model at all temperatures. Furthermore, by careful consideration of hyperfine contributions, we conclude that the original entropy measurements of Ramirez et al. are, after all, essentially correct: The short-time relaxation method used in that study gives a reasonably accurate estimate of the equilibrium spin ice entropy due to a cancellation of contributions.
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- Bramwell, Steven T., et al.
(författare)
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Phase order in superfluid helium films
- 2015
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Ingår i: Europhysics letters. - : IOP Publishing. - 0295-5075 .- 1286-4854. ; 112:5
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Tidskriftsartikel (refereegranskat)abstract
- Classic experimental data on helium films are transformed to estimate a finite-size phase order parameter that measures the thermal degradation of the condensate fraction in the two-dimensional superfluid. The order parameter is found to evolve thermally with the exponent beta = 3 pi(2)/128, a characteristic, in analogous magnetic systems, of the Berezinskii-Kosterlitz-Thouless (BKT) phase transition. Universal scaling near the BKT fixed point generates a collapse of experimental data on helium and ferromagnetic films, and implies new experiments and theoretical protocols to explore the phase order. These results give a striking example of experimental finite-size scaling in a critical system that is broadly relevant to two-dimensional Bose fluids. This paper is dedicated to the memory of our friend and colleague Maxime Clusel, with whom we enjoyed many stimulating discussions on related topics.
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- Kapaklis, Vassilios, et al.
(författare)
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Melting artificial spin ice
- 2012
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 14, s. 035009-
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Tidskriftsartikel (refereegranskat)abstract
- Artificial spin ice arrays of micromagnetic islands are a means of engineering additional energy scales and frustration into magnetic materials. Here we demonstrate a magnetic phase transition in an artificial square spin ice and use the symmetry of the lattice to verify the presence of excitations far below the ordering temperature. We do this by measuring the temperature dependent magnetisation in different principal directions and comparing with simulations of idealised statistical mechanical models. Our results confirm a dynamical pre-melting of the artificial spin ice structure at a temperature well below the intrinsic ordering temperature of the island material. We thus create a spin ice array that has real thermal dynamics of the artificial spins over an extended temperature range.
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- Taroni, Andrea, et al.
(författare)
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Universal window for two-dimensional critical exponents
- 2008
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 20:27, s. 275233-
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Forskningsöversikt (refereegranskat)abstract
- Two-dimensional condensed matter is realized in increasingly diverse forms that are accessible to experiment and of potential technological value. The properties of these systems are influenced by many length scales and reflect both generic physics and chemical detail. To unify their physical description is therefore a complex and important challenge. Here we investigate the distribution of experimentally estimated critical exponents, beta, that characterize the evolution of the order parameter through the ordering transition. The distribution is found to be bimodal and bounded within a window similar to 0.1 <= beta <= 0.25, facts that are only in partial agreement with the established theory of critical phenomena. In particular, the bounded nature of the distribution is impossible to reconcile with the existing theory for one of the major universality classes of two-dimensional behaviour - the XY model with four-fold crystal field - which predicts a spectrum of non-universal exponents bounded only from below. Through a combination of numerical and renormalization group arguments we resolve the contradiction between theory and experiment and demonstrate how the 'universal window' for critical exponents observed in experiment arises from a competition between marginal operators.
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- Turrini, A. A., et al.
(författare)
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Tunable critical correlations in kagome ice
- 2022
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 105:9
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive experimental and theoretical study of the kagome ice Coulomb phase that explores the fine-tuning of critical correlations by applied field, temperature, and crystal orientation. The continuous modification of algebraic correlations is observed by polarized neutron scattering experiments and is found to be well described by numerical simulations of an idealized model. We further clarify the thermodynamics of field-tuned Kasteleyn transitions and demonstrate some dramatic finite-size-scaling properties that depend on how topological string defects wind around the system boundaries. We conclude that kagome ice is a remarkable example of a critical and topological state in a real system that may be subject to fine experimental control.
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