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| 2. |
- Reisinger, Kerstin, et al.
(författare)
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Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.
- 2015
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 1879-3177 .- 0887-2333. ; 29:1, s. 259-270
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Tidskriftsartikel (refereegranskat)abstract
- The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitisation potency prediction. The results of the first phase - systematic evaluation of 16 test methods - are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data, potential for throughput, transferability and accessibility in cooperation with the test method developers. A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy - combined with bioavailability and skin metabolism data and exposure consideration - is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.
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| 3. |
- Bertl, Kristina, et al.
(författare)
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Soft tissue substitutes in non-root coverage procedures : a systematic review and meta-analysis
- 2017
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Ingår i: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 21:2, s. 505-518
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Forskningsöversikt (refereegranskat)abstract
- Objectives The present systematic review compared the effec- tiveness of soft tissue substitutes (STSs) and autogenous free gingival grafts (FGGs) in non-root-coverage procedures to increase keratinized tissue (KT) width around teeth. Materials and methods Included studies fulfilled the follow- ing main eligibility criteria: (a) preclinical in vivo or human controlled trials using FGG as control, (b) non-root-coverage procedures, and (c) assessment of KT width. Meta-analysis was performed on the gain in KT width (primary outcome variable) and several secondary variables. Results Eight human trials with short observation time evalu- ating five different STSs were identified. FGG yielded consis- tently significantly (p < 0.001) larger increase in KT width irrespective whether the comparison regarded an acellular ma- trix or a tissue-engineered STS. Further, FGG yielded consis- tently ≥2 mm KT width postoperatively, while use of STS did not, in the few studies reporting on this outcome. On the other hand, STSs resulted in significantly better aesthetic outcomes and received greater patient preference (p < 0.001). Conclusions Based on relatively limited evidence, in non- root-coverage procedures, FGG (1) resulted consistently in significantly larger increase in KT width compared to STS and (2) yielded consistently ≥2 mm KT width postoperatively, while STSs did not. STSs yielded significantly better aesthetic outcomes, received greater patient preference, and appeared safe. Clinical relevance Larger and more predictable increase in KT width is achieved with FGG, but STSs may be considered when aesthetics is important. Clinical studies reporting rele- vant posttreatment outcomes, e.g., postop KT width ≥2 mm, on the long-term (>6 months) are warranted.
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| 4. |
- Engström-Ruud, Linda, et al.
(författare)
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Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor.
- 2024
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Ingår i: Cell reports. - 2211-1247. ; 43:4
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Tidskriftsartikel (refereegranskat)abstract
- GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether GFRAL+ neurons acutely regulate glucose and energy homeostasis is, however, underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance, and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings indicate that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.
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| 5. |
- Fehlmann, Tobias, et al.
(författare)
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Common diseases alter the physiological age-related blood microRNA profile
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.
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| 8. |
- Karan, Sujoy, et al.
(författare)
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Superconducting quantum interference at the atomic scale
- 2022
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Ingår i: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 18:8, s. 893-
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Tidskriftsartikel (refereegranskat)abstract
- A single spin in a Josephson junction can reverse the flow of the supercurrent by changing the sign of the superconducting phase difference across it. At mesoscopic length scales, these pi-junctions are employed in various applications, such as finding the pairing symmetry of the underlying superconductor, as well as quantum computing. At the atomic scale, the counterpart of a single spin in a superconducting tunnel junction is known as a Yu-Shiba-Rusinov state. Observation of the supercurrent reversal in that setting has so far remained elusive. Here we demonstrate such a 0 to pi transition of a Josephson junction through a Yu-Shiba-Rusinov state as we continuously change the impurity-superconductor coupling. We detect the sign change in the critical current by exploiting a second transport channel as reference in analogy to a superconducting quantum interference device, which provides our scanning tunnelling microscope with the required phase sensitivity. The measured change in the Josephson current is a signature of the quantum phase transition and allows its characterization with high resolution. Continuously changing the coupling between a magnetic impurity and a superconductor allows the observation of the reversal of supercurrent flow at the atomic scale.
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| 9. |
- Kern, Ralph, et al.
(författare)
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Coulomb Excitation of Proton-rich N = 80 Isotones at HIE-ISOLDE
- 2020
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1555:1
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Tidskriftsartikel (refereegranskat)abstract
- A projectile Coulomb-excitation experiment was performed at the radioactive ion beam facility HIE-ISOLDE at CERN. The radioactive 140Nd and 142Sm ions were post accelerated to the energy of 4.62 MeV/A and impinged on a 1.45 mg/cm2-thin 208Pb target. The γ rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL. The scattered charged particles were detected by a double-sided silicon strip detector in forward direction. Experimental γ-ray intensities were used for the determination of electromagnetic transition matrix elements. Preliminary results for the reduced transition strength of the B(M1 23+ to 21+)=0.35(19) μN2 of 140Nd and a first estimation for 142Sm have been deduced using the Coulomb-excitation calculation software GOSIA. The 23+ states of 140Nd and 142Sm show indications of being the main fragment of the proton-neutron mixed-symmetry 21, ms+ state.
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| 10. |
- Kern, Ralph, et al.
(författare)
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Search for Isovector Valence-Shell Excitations in 140Nd and 142Sm via Coulomb excitation reactions of radioactive ion beams
- 2018
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Ingår i: International Conference on Nuclear Structure and Related Topics (NSRT18). - : EDP Sciences. - 2101-6275. ; 194
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Konferensbidrag (refereegranskat)abstract
- Projectile Coulomb excitation experiments were performed at HIE-ISOLDE at CERN with the radioactive ion beams of 140Nd and 142Sm. Ions with an energy of 4:62 MeV/A were impinging on a 1.45 mg/cm2 thick 208Pb target. The γ-rays depopulating the Coulomb-excited states were recorded by the HPGe-array MINIBALL and scattered particles were detected by a double-sided silicon strip detector. Experimental intensities were used for the determination of electromagnetic transition matrix elements. A preliminary result of the B(M1; 2+ 3 → 2+ 1) of 140Nd and an upper limit for the case of 142Sm are revealing the main fragments of the proton-neutron mixed-symmetry 2+ 1;ms states.
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