| 1. |
- 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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| 2. |
- Xie, Meng, et al.
(författare)
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Secondary ossification center induces and protects growth plate structure
- 2020
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.
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| 3. |
- Arneth, A., et al.
(författare)
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Historical carbon dioxide emissions caused by land-use changes are possibly larger than assumed
- 2017
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 10:2, s. 79-84
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Forskningsöversikt (refereegranskat)abstract
- The terrestrial biosphere absorbs about 20% of fossil-fuel CO 2 emissions. The overall magnitude of this sink is constrained by the difference between emissions, the rate of increase in atmospheric CO 2 concentrations, and the ocean sink. However, the land sink is actually composed of two largely counteracting fluxes that are poorly quantified: fluxes from land-use change and CO 2 uptake by terrestrial ecosystems. Dynamic global vegetation model simulations suggest that CO 2 emissions from land-use change have been substantially underestimated because processes such as tree harvesting and land clearing from shifting cultivation have not been considered. As the overall terrestrial sink is constrained, a larger net flux as a result of land-use change implies that terrestrial uptake of CO 2 is also larger, and that terrestrial ecosystems might have greater potential to sequester carbon in the future. Consequently, reforestation projects and efforts to avoid further deforestation could represent important mitigation pathways, with co-benefits for biodiversity. It is unclear whether a larger land carbon sink can be reconciled with our current understanding of terrestrial carbon cycling. Our possible underestimation of the historical residual terrestrial carbon sink adds further uncertainty to our capacity to predict the future of terrestrial carbon uptake and losses.
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| 5. |
- Liu, Hailong, et al.
(författare)
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Computational and experimental characterization of 3D-printed PCL structures toward the design of soft biological tissue scaffolds
- 2020
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- Degradable porous polymeric structures are attractive candidates for biological tissue scaffolds, and adequate mechanical, transport, chemical and biological properties determine their functionality. Aside from the properties of polymer-based materials, the scaffold's meso-structure controls its elasticity at the organ length-scale. This study investigated the effect of the meso-structure on scaffolds' mechanical and transport properties using finite element analysis (FEA) and computational fluid dynamics (CFD). A number of poly (ε-caprolactone) (PCL) - based scaffolds were 3D printed, analyzed by microcomputed tomography (micro-CT) and mechanically tested. We found that the gradient (G) and gradient and staggered (GS) meso-structure designs led to a higher scaffold permeability, a more homogeneous flow inside the scaffold, and a lower wall shear stress (WSS) in comparison with the basic (B) meso-structure design. The GS design resulted in scaffold stiffness as low as 1.07/0.97 MPa under compression/tension, figures that are comparative with several soft tissues. Image processing of micro-CT data demonstrated that the imposed meso-structures could have been adequately realized through 3D printing, and experimental testing validated FEA analysis. Our results suggest that the properties of 3D-printed PCL-based scaffolds can be tuned via meso-structures toward soft tissue engineering applications. The biological function of designed scaffolds should be further explored in-situ studies.
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| 6. |
- Martufi, Giampaolo, et al.
(författare)
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A constitutive model for vascular tissue that integrates fibril, fiber and continuum levels with application to the isotropic and passive properties of the infrarenal aorta
- 2011
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 44:14, s. 2544-2550
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental understanding of the mechanical properties of the extracellular matrix (ECM) is critically important to quantify the amount of macroscopic stress and/or strain transmitted to the cellular level of vascular tissue. Structural constitutive models integrate histological and mechanical information, and hence, allocate stress and strain to the different microstructural components of the vascular wall. The present work proposes a novel multi-scale structural constitutive model of passive vascular tissue, where collagen fibers are assembled by proteoglycan (PG) cross-linked collagen fibrils and reinforce an otherwise isotropic matrix material. Multiplicative kinematics account for the straightening and stretching of collagen fibrils, and an orientation density function captures the spatial organization of collagen fibers in the tissue. Mechanical and structural assumptions at the collagen fibril level define a piece-wise analytical stress-stretch response of collagen fibers, which in turn is integrated over the unit sphere to constitute the tissue's macroscopic mechanical properties. The proposed model displays the salient macroscopic features of vascular tissue, and employs the material and structural parameters of clear physical meaning. Likewise, the constitutive concept renders a highly efficient multi-scale structural approach that allows for the numerical analysis at the organ level. Model parameters were estimated from isotropic mean-population data of the normal and aneurysmatic aortic wall and used to predict in-vivo stress states of patient-specific vascular geometries, thought to demonstrate the robustness of the particular Finite Element (FE) implementation. The collagen fibril level of the multi-scale constitutive formulation provided an interface to integrate vascular wall biology and to account for collagen turnover.
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