| 1. |
- Carlström, Karl E., et al.
(författare)
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Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate
- 2020
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Ingår i: NEUROTHERAPEUTICS. - : SPRINGER. - 1933-7213 .- 1878-7479. ; 17, s. 1142-1152
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Tidskriftsartikel (refereegranskat)abstract
- The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1-CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NF kappa B, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.
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| 2. |
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| 3. |
- Hoff, D., et al.
(författare)
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Quantum Beat Spectroscopy of Helium Photoelectrons
- 2023
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Ingår i: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - 9798350345995
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Konferensbidrag (refereegranskat)abstract
- The availability of broadband extreme ultraviolet light sources allows for investigation of electron wave-packets from high lying bound states in atoms [1,2]. The dynamics of these states can be mapped out in the ionization continuum with an overlapping infrared field, which may also uncover new, light induced, dressed states [3]. Here, we carry out a complete characterization of these electron wave-packets using a small number of attosecond pulses.
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| 4. |
- Köhler, Christian, et al.
(författare)
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Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:29
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Tidskriftsartikel (refereegranskat)abstract
- Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmission pathway, whereas substitution of the entire pharmacophore leads to divergent allosteric control by apparently rewiring the communication network. Our results provide key insights that should aid in the design of mechanistically differentiated ligands.
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| 5. |
- Misztal-Okońska, P., et al.
(författare)
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Importance of immediate electronic-based feedback to enhance feedback for first-time cpr trainees
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Sudden cardiac arrest is one of the leading causes of death globally. The recommended clinical management in out-of-hospital cardiac arrest cases is the immediate initiation of high-qual-ity cardiopulmonary resuscitation (CPR). Training mannequins should be combined with technology that provides students with detailed immediate feedback on the quality of CPR performance. This study aimed to verify the impacts of the type of feedback (basic or detailed) the responders receive from the device while learning CPR and how it influences the quality of their performance and the motivation to improve their skills. The study was conducted at the Medical University of Lublin among 694 multi-professional health students during first aid classes on basic life support (BLS). The students first practiced on an adult mannequin with a basic control panel; afterward, the same mannequin was connected to a laptop, ensuring a detailed record of the performed activities through a projector. Next, the participants expressed their subjective opinion on how the feedback provided during the classes, basic vs. detailed, motivated them to improve the quality of their CPR performance. Additionally, during the classes, the instructor conducted an extended observation of students’ work and behavior. In the students’ opinion, the CPR training with detailed feedback devices provided motivation for learning and improving CPR proficiency than that with a basic control panel. Furthermore, the comments given from devices seemed to be more acceptable to the students, who did not see any bias in the device’s evaluation compared to that of the instructor. Detailed device feedback motivates student health practitioners to learn and improve the overall quality of CPR. The use of mannequins that provide detailed feedback during BLS courses can improve survival in out-of-hospital cardiac arrest. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 6. |
- Nandi, Saikat, et al.
(författare)
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Observation of Rabi dynamics with a short-wavelength free-electron laser
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 608:7923
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Tidskriftsartikel (refereegranskat)abstract
- Rabi oscillations are periodic modulations of populations in two-level systems interacting with a time-varying field(1). They are ubiquitous in physics with applications in different areas such as photonics(2), nano-electronics(3), electron microscopy(4) and quantum information(5). While the theory developed by Rabi was intended for fermions in gyrating magnetic fields, Autler and Townes realized that it could also be used to describe coherent light-matter interactions within the rotating-wave approximation(6). Although intense nanometre-wavelength light sources have been available for more than a decade(7-9), Rabi dynamics at such short wavelengths has not been directly observed. Here we show that femtosecond extreme-ultraviolet pulses from a seeded free-electron laser(10) can drive Rabi dynamics between the ground state and an excited state in helium atoms. The measured photoelectron signal reveals an Autler-Townes doublet and an avoided crossing, phenomena that are both fundamental to coherent atom-field interactions(11). Using an analytical model derived from perturbation theory on top of the Rabi model, we find that the ultrafast build-up of the doublet structure carries the signature of a quantum interference effect between resonant and non-resonant photoionization pathways. Given the recent availability of intense attosecond(12) and few-femtosecond(13) extreme-ultraviolet pulses, our results unfold opportunities to carry out ultrafast manipulation of coherent processes at short wavelengths using free-electron lasers.
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| 7. |
- Unger, B., et al.
(författare)
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MiniSCANS-II: Aerial survey for harbour porpoises in the western Baltic Sea, Belt Sea, the Sound and Kattegat in 2020 : Joint survey by Denmark, Germany and Sweden. Final report to Danish Environmental Protection Agency, German Federal Agency for Nature Conservation and Swedish Agency for Marine and Water Management.
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Marine Strategy Framework Directive (MSFD) (Directive 2008/56/EC) emphasises the need for cross-border monitoring of wide-ranging species, such as the harbour porpoise (Phocoena phocoena), the most abundant cetacean species occurring year-round in the Baltic Sea. In June and July 2020, Germany, Denmark, and Sweden conducted a dedicated large-scale aerial survey (called MiniSCANS-II) for harbour porpoises in the management area of the Belt Sea population, i.e., between an east-west line between Denmark and Sweden at 56.95°N in the Kattegat Sea, and a north-south line between Sweden and Germany at 13.5°E in the southern Baltic Sea. This survey followed line-transect distance sampling methodology according to the SCANS protocol to derive an unbiased absolute abundance estimate. With a realised effort of 4,533 km in nine strata, the observers recorded a total of 202 sightings (251 individuals, of these 16 were calves). The large majority of survey effort (91.2%) was conducted in either good or moderate sighting conditions. The abundance of the Belt Sea population was estimated to be 17,301 harbour porpoises (95% CI = 11,695-25,688; CV = 0.20), with an average density of 0.41 individuals/km² (95% CI = 0.28-0.61). This is the lowest abundance estimate since the first (SCANS) survey was conducted in 1994. However, the variance (especially of the earlier abundance estimates) is high, and a dedicated trend analysis needs to be conducted to determine if there has been a decline in the population abundance over time. The results should raise some concern about the status of the population and emphasise the importance of repeated surveys in the near future to increase the time series of robust abundance estimates available. Such time series are essential for monitoring the progress of the population towards achieving favourable conservation status under the Habitats Directive and good environmental status (GES) as demanded by the MSFD.
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