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- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 4. |
- Bergström, Sofia, et al.
(författare)
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A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers : a GENFI study
- 2021
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Ingår i: Molecular Neurodegeneration. - : Springer Nature. - 1750-1326. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.
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- Bourgoin, M., et al.
(författare)
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Investigation of the small-scale statistics of turbulence in the Modane S1MA wind tunnel
- 2018
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Ingår i: CEAS Aeronautical Journal. - : Springer. - 1869-5582 .- 1869-5590. ; 9:2, s. 269-281
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Tidskriftsartikel (refereegranskat)abstract
- This article describes the planning, set-up, turbulence characterization and analysis of measurements of a passive grid turbulence experiment that was carried out in the S1MA wind-tunnel from ONERA in Modane, in the context of the ESWIRP European project. This experiment aims at a detailed investigation of the statistical properties of turbulent flows at large Reynolds numbers. The primary goal is to take advantage of the unequaled large-scale dimensions of the ONERA S1MA wind-tunnel facility, to make available to the broad turbulence community high-quality experimental turbulence data with unprecendented resolution (both spatial and temporal) and accuracy (in terms of statistical convergence). With this goal, we designed the largest grid-generated turbulence experiment planned and performed to date. Grid turbulence is a canonical flow known to produce almost perfectly homogeneous and isotropic turbulence (HIT) which remains a unique framework to investigate fundamental physics of turbulent flows. Here, we present a brief description of the measurements, in particular those based on hot-wire diagnosis. By comparing results from classical hot-wires and from a nano-fabricated wire (developed at Princeton University), we show that our goal of resolving down to the smallest dissipative scales of the flow has been achieved. We also present the full characterization of the turbulence here, in terms of turbulent energy dissipation rate, injection and dissipation scales (both spatial and temporal) and Reynolds number.
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