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- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Harada, Yoshihisa, et al.
(författare)
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Selective Probing of the OH or OD Stretch Vibration in Liquid Water Using Resonant Inelastic Soft-X-Ray Scattering
- 2013
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 111:19, s. 193001-
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Tidskriftsartikel (refereegranskat)abstract
- High-resolution O 1s resonant inelastic x-ray scattering spectra of liquid H2O, D2O, and HDO, obtained by excitation near the preedge resonance show, in the elastic line region, well-separated multiple vibrational structures corresponding to the internal OH stretch vibration in the ground state of water. The energy of the first-order vibrational excitation is strongly blueshifted with respect to the main band in the infrared or Raman spectra of water, indicating that water molecules with a highly weakened or broken donating hydrogen bond are correlated with the preedge structure in the x-ray absorption spectrum. The vibrational profile of preedge excited HDO water is well fitted with 50% +/- 20% greater OH-stretch contribution compared to OD, which strongly supports a preference for OH being the weakened or broken H-bond in agreement with the well-known picture that D2O makes stronger H-bonds than H2O. Accompanying path-integral molecular dynamics simulations show that this is particularly the case for strongly asymmetrically H-bonded molecules, i.e., those that are selected by preedge excitation.
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- Kimberg, Victor, et al.
(författare)
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Rydberg-valence mixing and interchannel coupling in resonant oxygen 1s inelastic x-ray scattering of O_2
- 2012
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - : American Physical Society. - 1050-2947 .- 1094-1622. ; 85:3
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Tidskriftsartikel (refereegranskat)abstract
- Rydberg-valence (RV) mixing and doublet-quartet (DQ) interchannel coupling in the core-excited states of triplet open-shell O2 are experimentally and theoretically unveiled through the resonant inelastic x-ray scattering around the O 1s→σ∗u resonance. Ab initio calculations explain complicated excitation energy dependence of the spectral profile by the interplay of the DQ interchannel coupling under the presence of the RV mixing. Complicated intermediate states with valence and/or Rydberg character are successfully analyzed through the filtering of pure valence and pure Rydberg final states.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Kobayashi, Takahiro, et al.
(författare)
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Revealing the Hidden Spin-Polarized Bands in a Superconducting Tl Bilayer Crystal
- 2023
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Ingår i: Nano Letters. - 1530-6992 .- 1530-6984. ; 23:16, s. 7675-7682
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Tidskriftsartikel (refereegranskat)abstract
- The interplay of spin-orbit coupling and crystal symmetry can generate spin-polarized bands in materials only a few atomic layers thick, potentially leading to unprecedented physical properties. In the case of bilayer materials with global inversion symmetry, locally broken inversion symmetry can generate degenerate spin-polarized bands, in which the spins in each layer are oppositely polarized. Here, we demonstrate that the hidden spins in a Tl bilayer crystal are revealed by growing it on Ag(111) of sizable lattice mismatch, together with the appearance of a remarkable phenomenon unique to centrosymmetric hidden-spin bilayer crystals: a novel band splitting in both spin and space. The key to success in observing this novel splitting is that the interaction at the interface has just the right strength: it does not destroy the original wave functions of the Tl bilayer but is strong enough to induce an energy separation.
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- Nilsson, Anders, et al.
(författare)
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Resonant inelastic X-ray scattering of liquid water
- 2013
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 188, s. 84-100
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Tidskriftsartikel (refereegranskat)abstract
- We review recent studies using resonant inelastic X-ray scattering (RIXS) or also here denoted X-ray emission spectroscopy (XES) on liquid water and the assignment of the two sharp peaks in the lone-pair region. Using the excitation energy dependence we connect the two peaks to specific features in the Xray absorption (XAS) spectrum which have independently been assigned to molecules in tetrahedral or distorted configurations. The polarization dependence shows that both peaks are of 1b(1) origin supporting an interpretation in terms of two structural species, tetrahedral or disordered, which is furthermore consistent with the temperature-dependence of the two peaks. We discuss effects of life-time vibrational interference and how this affects the two components differently and also leads to differences in the relative peak heights for H2O and D2O. We show furthermore that the inherent structure in molecular dynamics simulations contain the structural bimodality suggested by XES, but this is smeared out in the real structure when temperature is included. We present a discussion around alternative interpretations suggesting that the origin of the two peaks is related to ultrafast dissociation and show evidence that such a model is inconsistent with several experimental observations and theoretical concepts. We conclude that the peaks reflect a temperature-dependent balance in fluctuations between tetrahedral and disordered structures in the liquid. This is well-aligned with theories of water under supercooled conditions and higher pressures where water might exist as high- or low-density liquid with different possibilities for a transition between them. With the present work we provide a link between established models for supercooled water, where water's anomalies become extreme, and ambient water, where the anomalous contributions are weaker but still important.
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- Tian, Shangjie, et al.
(författare)
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Magnetic topological insulator MnBi6 Te10 with a zero-field ferromagnetic state and gapped Dirac surface states
- 2020
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Ingår i: Physical Review B. - 2469-9950. ; 102:3
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic topological insulators (TIs) with nontrivial topological electronic structure and broken time-reversal symmetry exhibit various exotic topological quantum phenomena. The realization of such exotic phenomena at high temperature is one of the central topics in this area. We reveal that MnBi6Te10 is a magnetic TI with an antiferromagnetic ground state below 10.8 K whose nontrivial topology is manifested by Dirac-like surface states. The ferromagnetic axion insulator state with Z4=2 emerges once spins are polarized at a field as low as 0.1 T, accompanied with saturated anomalous Hall resistivity up to 10 K. Such a ferromagnetic state is preserved even with an external field down to zero at 2 K. Theoretical calculations indicate that the few-layer ferromagnetic MnBi6Te10 is also topologically nontrivial with a nonzero Chern number. Angle-resolved photoemission spectroscopy experiments further reveal three types of Dirac surface states arising from different terminations on the cleavage surfaces, one of which has insulating behavior with an energy gap of ∼28 meV at the Dirac point. These outstanding features suggest that MnBi6Te10 is a promising system to realize various topological quantum effects at zero field and high temperature.
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- Tokushima, Takashi, et al.
(författare)
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High resolution X-ray emission spectroscopy of water and its assignment based on two structural motifs
- 2010
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 177:03-feb, s. 192-205
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate proposed interpretations of previous X-ray emission spectroscopy (XES) data on liquid water. The split peak in the lone-pair orbital region has been interpreted in terms of either two different structural motifs, tetrahedral and distorted, or as due to core-hole-induced dissociative dynamics; here we add new data on a 1:1 H2O/D2O isotopic mixture and additional spectrum simulations including the core-hole-induced dynamics. The XES spectrum of HDO is quite nicely reproduced as the sum of spectra of H2O and D2O, which we interpret as that core-hole-induced dynamics contribute only to the peak shape and do not affect the intensity ratio between tetrahedrally coordinated and distorted. We find the simulation-based interpretation of the two lone-pair peaks as being of completely different symmetries, molecular 1b(1) and dissociated 3a(1), difficult to reconcile with the experimental intensities in the 1b(2) and 3a(1) spectral regions. We report extensive theoretical simulations of spectra probing both the distance and velocity quantum distributions of the internal OH stretch; sharp features not associated with the lone-pair, that are seen when the OH stretch is treated as a classical oscillator, become smeared out when the zero-point Franck-Condon profile and momentum distribution in the v=0 level of the OH stretch are taken into account. This demonstrates that neglecting zero-point motion in simulating XES spectra of water generates artificially sharp structures. XES spectra of 1 M and 4 M hydrochloric acid (HCl) and sodium hydroxide (NaOH) are reported. These spectra indicate that dissociated species most likely can be excluded as the origin of the double 1b(1) peak structure. We thus argue that the experimental observation of two distinct peaks in the lone-pair region is less likely to be explained by an unstructured continuum model of the liquid, but is easily explained within a two-component fluctuating model.
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- Tokushima, Takashi, et al.
(författare)
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Polarization dependent resonant x-ray emission spectroscopy of D2O and H2O water : Assignment of the local molecular orbital symmetry
- 2012
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 136:4, s. 044517-
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Tidskriftsartikel (refereegranskat)abstract
- The polarization dependence of the split two peaks in the lone-pair region in the x-ray emission spectra has been determined at several different excitation energies for both D2O and H2O water. In contrast to predictions based on a narrow range of local water structures where the two peaks would be of different molecular orbital symmetry and arise from, respectively, intact and dissociated molecules, we show that the two peaks in the lone-pair region are both of lone-pair 1b(1) orbital symmetry. The results support the interpretation that the two peaks appear due to fluctuations between two distinct different main structural environments.
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