| 1. |
- Bonekamp, N. A., et al.
(författare)
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Small-molecule inhibitors of human mitochondrial DNA transcription
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 588, s. 712-716
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Tidskriftsartikel (refereegranskat)abstract
- Altered expression of mitochondrial DNA (mtDNA) occurs in ageing and a range of human pathologies (for example, inborn errors of metabolism, neurodegeneration and cancer). Here we describe first-in-class specific inhibitors of mitochondrial transcription (IMTs) that target the human mitochondrial RNA polymerase (POLRMT), which is essential for biogenesis of the oxidative phosphorylation (OXPHOS) system(1-6). The IMTs efficiently impair mtDNA transcription in a reconstituted recombinant system and cause a dose-dependent inhibition of mtDNA expression and OXPHOS in cell lines. To verify the cellular target, we performed exome sequencing of mutagenized cells and identified a cluster of amino acid substitutions in POLRMT that cause resistance to IMTs. We obtained a cryo-electron microscopy (cryo-EM) structure of POLRMT bound to an IMT, which further defined the allosteric binding site near the active centre cleft of POLRMT. The growth of cancer cells and the persistence of therapy-resistant cancer stem cells has previously been reported to depend on OXPHOS7-17, and we therefore investigated whether IMTs have anti-tumour effects. Four weeks of oral treatment with an IMT is well-tolerated in mice and does not cause OXPHOS dysfunction or toxicity in normal tissues, despite inducing a strong anti-tumour response in xenografts of human cancer cells. In summary, IMTs provide a potent and specific chemical biology tool to study the role of mtDNA expression in physiology and disease. Inhibitors of mitochondrial transcription that target human mitochondrial RNA polymerase provide a chemical biology tool for studying the role of mitochondrial DNA expression in a wide range of pathologies.
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| 5. |
- Erdelyi, Mate, 1975, et al.
(författare)
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The Binding Mode of Side Chain- and C3-Modified Epothilones to Tubulin
- 2010
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 5:6, s. 911-920
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Tidskriftsartikel (refereegranskat)abstract
- The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of -His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.
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| 6. |
- Ferrari, P., et al.
(författare)
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Work-in-Progress : Compromising Security of Real-time Ethernet Devices by means of Selective Queue Saturation Attack
- 2020
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Ingår i: Proceedings. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728152974
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Konferensbidrag (refereegranskat)abstract
- The industrial control systems (ICS) are using Real-Time Ethernet (RTE) protocols for many years. Today, Ethernet based control systems are widely used in industries. The Time Sensitive Networking (TSN) initiative will definitely push their further diffusion. With the introduction of Industry 4.0, production machines and their components have been connected to the Internet. Currently adopted RTE protocols do not require authentication, and hence may exchange data also with potentially malicious partners. In this paper, a selective Denial of Service (DoS) attack is presented. The proposed Selective Queue Saturation Attack (SQSA) is aimed to jam the message queue of the RTE communication stack in selected devices. The SQSA minimizes the chances of being detected by keeping its requirements (in term generated traffic) as low as possible. The SQSA has been applied to a real scenario based on PROFINET. The results of the use case demonstrate: the feasibility of the proposed attack; the reduced footprint compared to known DoS attacks (more than one thousand times less); and the selectivity of the attack, which can disrupt the realtime behavior of even a single target node inside the RTE network. © 2020 IEEE.
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| 7. |
- Galeski, S., et al.
(författare)
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Origin of the quasi-quantized Hall effect in ZrTe 5
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The quantum Hall effect (QHE) is traditionally considered to be a purely two-dimensional (2D) phenomenon. Recently, however, a three-dimensional (3D) version of the QHE was reported in the Dirac semimetal ZrTe . It was proposed to arise from a magnetic-field-driven Fermi surface instability, transforming the original 3D electron system into a stack of 2D sheets. Here, we report thermodynamic, spectroscopic, thermoelectric and charge transport measurements on such ZrTe samples. The measured properties: magnetization, ultrasound propagation, scanning tunneling spectroscopy, and Raman spectroscopy, show no signatures of a Fermi surface instability, consistent with in-field single crystal X-ray diffraction. Instead, a direct comparison of the experimental data with linear response calculations based on an effective 3D Dirac Hamiltonian suggests that the quasi-quantization of the observed Hall response emerges from the interplay of the intrinsic properties of the ZrTe electronic structure and its Dirac-type semi-metallic character.
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| 8. |
- Ibarra, R., et al.
(författare)
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Noncollinear magnetic order in epitaxial thin films of the centrosymmetric MnPtGa hard magnet
- 2022
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Ingår i: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 120:17
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic systems exhibiting spin-canted states have garnered much attention recently for their promising rich exotic properties driven by the real-space spin textures and competing magnetic orders. In this study, we present the structural and magnetic properties of hexagonal 60 nm MnPtGa epitaxial thin films grown by magnetron sputtering on Al2O3(0001) single-crystalline substrates. The MnPtGa film crystallizes in the centrosymmetric P6(3)/mmc (No. 194) space group, showing perpendicular magnetic anisotropy along the c-axis, with a Curie temperature T-C = 263 K. In addition, the MnPtGa film undergoes a spin reorientation transition at T-sr = 160 K. We investigated the MnPtGa magnetic ground states using single-crystal neutron diffraction. A structurally forbidden (001) magnetic Bragg reflection emerges below T-sr, indicating the existence of a spin-canted state, where the magnetic moments align ferromagnetically perpendicular to the basal plane, and a non-zero in-plane component exhibits an antiferromagnetic ordering along the c-axis. At 2 K, the refined magnetic moments of Mn are mu(z) = 4.2(4) mu(B) and mu(x) = 1.5(3) mu(B), projected onto the c-axis and basal plane, respectively. Hence, we determined a 20 degrees Mn spin canting angle off from the c-axis.
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| 9. |
- Belopolski, Ilya, et al.
(författare)
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Observation of a linked-loop quantum state in a topological magnet
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 604:7907, s. 647-652
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Tidskriftsartikel (refereegranskat)abstract
- Quantum phases can be classified by topological invariants, which take on discrete values capturing global information about the quantum state1–13. Over the past decades, these invariants have come to play a central role in describing matter, providing the foundation for understanding superfluids5, magnets6,7, the quantum Hall effect3,8, topological insulators9,10, Weyl semimetals11–13 and other phenomena. Here we report an unusual linking-number (knot theory) invariant associated with loops of electronic band crossings in a mirror-symmetric ferromagnet14–20. Using state-of-the-art spectroscopic methods, we directly observe three intertwined degeneracy loops in the material’s three-torus, T3, bulk Brillouin zone. We find that each loop links each other loop twice. Through systematic spectroscopic investigation of this linked-loop quantum state, we explicitly draw its link diagram and conclude, in analogy with knot theory, that it exhibits the linking number (2, 2, 2), providing a direct determination of the invariant structure from the experimental data. We further predict and observe, on the surface of our samples, Seifert boundary states protected by the bulk linked loops, suggestive of a remarkable Seifert bulk–boundary correspondence. Our observation of a quantum loop link motivates the application of knot theory to the exploration of magnetic and superconducting quantum matter.
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| 10. |
- Felser, C, et al.
(författare)
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Metal valence states in Eu0.7NbO3, EuNbO3, and Eu2Nb5O9 by TB-LMTO-ASA band-structure calculations and resonant photoemission spectroscopy
- 1998
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 57, s. 1510-1514
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structures of Eu2Nb5O9, EuNbO3, and Eu0.7NbO3 have been investigated by photoemission and total-yield spectroscopy with synchrotron radiation, and in the case of Eu2Nb5O9 by tight-binding linear muffin-tin orbital (LMTO) band-structure calculations. A central question for reduced europium niobates is that of the valence of Eu and Nb. Both europium and niobium atoms can appear in different valence states so that various electronic configurations in the title compounds are possible. For this reason, the valence band was studied by the resonant Eu 4d⃗4f technique to determine the Eu valence. The final-state 4f6 multiplet of divalent Eu is dominant in all spectra. Since there are no 4f density of states at the Fermi level, valence fluctuations are not expected. The niobium valence states were investigated by core-level spectroscopy. We found only one 3d5/23d3/2 doublet for the Nb 3d core level in EuNbO3 and Eu0.7NbO3, while in Eu2Nb5O9, two 3d doublets have been observed, corresponding to two chemically distinct niobium atoms in this compound. The 3d5/2 peak in EuNbO3 is assigned to the +4 nominal valence state at a binding energy of 209.7 eV. The doublet of Eu0.7NbO3 is observed at 0.5 eV higher binding energy (at 210.2 eV), which then corresponds to a nominal Nb+4+δ chemical state. In Eu2Nb5O9, the valence of Nb in the NbO6 octahedra is less than +5 and in the Nb6O12 clusters is close to +2 as expected. This is in accordance with the LMTO band-structure calculations
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| 11. |
- Krieger, Jonas A., et al.
(författare)
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Weyl spin-momentum locking in a chiral topological semimetal
- 2024
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Ingår i: Nature Communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Spin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking – a directional relationship between an electron’s spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions. Here, we use spin- and angle-resolved photoemission spectroscopy to evidence Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. We find that the electron spin of the Fermi arc surface states is orthogonal to their Fermi surface contour for momenta close to the projection of the bulk multifold fermion at the Γ point, which is consistent with Weyl spin-momentum locking of the latter. The direct measurement of the bulk spin texture of the multifold fermion at the R point also displays Weyl spin-momentum locking. The discovery of Weyl spin-momentum locking may lead to energy-efficient memory devices and Josephson diodes based on chiral topological semimetals.
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| 12. |
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| 13. |
- Ryan, Sinéad A., et al.
(författare)
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Optically controlling the competition between spin flips and intersite spin transfer in a Heusler half-metal on sub-100-fs time scales
- 2023
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:45, s. 1428-
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Tidskriftsartikel (refereegranskat)abstract
- The direct manipulation of spins via light may provide a path toward ultrafast energy-efficient devices. However, distinguishing the microscopic processes that can occur during ultrafast laser excitation in magnetic alloys is challenging. Here, we study the Heusler compound Co2MnGa, a material that exhibits very strong light-induced spin transfers across the entire M-edge. By combining the element specificity of extreme ultraviolet high-harmonic probes with time-dependent density functional theory, we disentangle the competition between three ultrafast light-induced processes that occur in Co2MnGa: same-site Co-Co spin transfer, intersite Co-Mn spin transfer, and ultrafast spin flips mediated by spin-orbit coupling. By measuring the dynamic magnetic asymmetry across the entire M-edges of the two magnetic sublattices involved, we uncover the relative dominance of these processes at different probe energy regions and times during the laser pulse. Our combined approach enables a comprehensive microscopic interpretation of laser-induced magnetization dynamics on time scales shorter than 100 femtoseconds.
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