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- Law, Andrew M. K., et al.
(författare)
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ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo
- 2022
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Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844. ; 9:21
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Tidskriftsartikel (refereegranskat)abstract
- To fully investigate cellular responses to stimuli and perturbations within tissues, it is essential to replicate the complex molecular interactions within the local microenvironment of cellular niches. Here, the authors introduce Alginate-based tissue engineering (ALTEN), a biomimetic tissue platform that allows ex vivo analysis of explanted tissue biopsies. This method preserves the original characteristics of the source tissue's cellular milieu, allowing multiple and diverse cell types to be maintained over an extended period of time. As a result, ALTEN enables rapid and faithful characterization of perturbations across specific cell types within a tissue. Importantly, using single-cell genomics, this approach provides integrated cellular responses at the resolution of individual cells. ALTEN is a powerful tool for the analysis of cellular responses upon exposure to cytotoxic agents and immunomodulators. Additionally, ALTEN's scalability using automated microfluidic devices for tissue encapsulation and subsequent transport, to enable centralized high-throughput analysis of samples gathered by large-scale multicenter studies, is shown.
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| 2. |
- Yaghootkar, Hanieh, et al.
(författare)
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Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:12, s. 2806-2818
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Tidskriftsartikel (refereegranskat)abstract
- Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
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| 3. |
- Zhou, Xing, et al.
(författare)
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Loads experienced by a Francis turbine during short and fast transient under part load operation
- 2024
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Ingår i: Physics of fluids. - : American Institute of Physics (AIP). - 1070-6631 .- 1089-7666. ; 36:8
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Tidskriftsartikel (refereegranskat)abstract
- As hydropower is integrated into the renewable energy system, the turbine components are liable to many loads variation for regulation. The loads experienced under transient operation need to be accounted for and understood to develop adequate mitigation technique and strategies. To identify possible risks occurring during such short and fast transients, we investigate the nonlinear growth and time delay effects of pressure fluctuations, as well as the unsteady flow field evolution for a Francis turbine under load reduction in the part load regime. A two-stage transient process analytical framework is proposed via signal processing and vortex identification methods, including main transient and post-transient stages. In the main transient stage, the dominant frequency of pressure fluctuations within the draft tube shifts from 0.32·fn to 0.24·fn, accompanied by a fivefold increase in the amplitude. Furthermore, low-frequency pressure fluctuations in a wider range are identified (0-2·fn), source of possible resonance of power plant structures. The maximum pressure is reached in the post-transient stage after the end of the guide vane closure and is 50% larger than the maximum value in the main transient stage. When comparing the two components of pressure fluctuations within the draft tube, the synchronous component increases slowly but reaches the peak faster, which can be explained by the evolution of instantaneous vortex structure investigated with proper orthogonal decomposition. The findings are useful to ascertain possible risk factors along with the investigation of the evolution of non-stationary flow field in the context of frequent turbine load variations.
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