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| 2. |
- Helker, Christian S M, et al.
(författare)
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A whole organism small molecule screen identifies novel regulators of pancreatic endocrine development.
- 2019
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Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 146:14
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Tidskriftsartikel (refereegranskat)abstract
- An early step in pancreas development is marked by the expression of the transcription factor Pdx1 within the pancreatic endoderm, where it is required for the specification of all endocrine cell types. Subsequently, Pdx1 expression becomes restricted to the β-cell lineage, where it plays a central role in β-cell function. This pivotal role of Pdx1 at various stages of pancreas development makes it an attractive target to enhance pancreatic β-cell differentiation and increase β-cell function. In this study, we used a newly generated zebrafish reporter to screen over 8000 small molecules for modulators of pdx1 expression. We found four hit compounds and validated their efficacy at different stages of pancreas development. Notably, valproic acid treatment increased pancreatic endoderm formation, while inhibition of TGFβ signaling led to α-cell to β-cell transdifferentiation. HC toxin, another HDAC inhibitor, enhances β-cell function in primary mouse and human islets. Thus, using a whole organism screening strategy, this study identified new pdx1 expression modulators that can be used to influence different steps in pancreas and β-cell development.
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| 3. |
- Klarbring, Anders, et al.
(författare)
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Shakedown of discrete systems involving plasticity and friction
- 2017
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Ingår i: European journal of mechanics. A, Solids. - : ELSEVIER SCIENCE BV. - 0997-7538 .- 1873-7285. ; 64, s. 160-164
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Tidskriftsartikel (refereegranskat)abstract
- In associated plasticity, systems subjected to cyclic loading are sometimes predicted to shake down, meaning that, after some dissipative cycles, the response goes back to a purely elastic state, where no plastic flow occurs. Frictional systems show a similar behaviour, in the sense that frictional slips due to the external loads may cease after some cycles. It has been proved that, for complete contacts with elastic behaviour and Coulomb friction, Melans theorem gives a sufficient condition for the system to shake down, if and only if there is no normal-tangential coupling at the interfaces. In this paper, the case of discrete systems combining elastic-plastic behaviour and Coulomb friction is considered. In particular, it is proved that Melans theorem still holds for contact-wise uncoupled systems, i.e., the existence of a residual state, comprised of frictional slips and plastic strains, is a sufficient condition for the system to shake down. (C) 2017 Elsevier Masson SAS. All rights reserved.
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| 4. |
- Spagnoli, A., et al.
(författare)
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Non-linear programming in shakedown analysis with plasticity and friction
- 2017
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Ingår i: Journal of the mechanics and physics of solids. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0022-5096 .- 1873-4782. ; 104, s. 71-83
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Tidskriftsartikel (refereegranskat)abstract
- Complete frictional contacts, when subjected to cyclic loading, may sometimes develop a favourable situation where slip ceases after a few cycles, an occurrence commonly known as frictional shakedown. Its resemblance to shakedown in plasticity has prompted scholars to apply direct methods, derived from the classical theorems of limit analysis, in order to assess a safe limit to the external loads applied on the system. In circumstances where zones of plastic deformation develop in the material (e.g., because of the large stress concentrations near the sharp edges of a complete contact), it is reasonable to expect an effect of mutual interaction of frictional slip and plastic strains on the load limit below which the global behaviour is non dissipative, i.e., both slip and plastic strains go to zero after some dissipative load cycles. In this paper, shakedown of general two-dimensional discrete systems, involving both friction and plasticity, is discussed and the shakedown limit load is calculated using a non-linear programming algorithm based on the static theorem of limit analysis. An illustrative example related to an elastic-plastic solid containing a frictional crack is provided. (C) 2017 Elsevier Ltd. All rights reserved.
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| 5. |
- Spagnoli, A., et al.
(författare)
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Shakedown in an elastic-plastic solid with a frictional crack
- 2016
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Ingår i: Procedia Structural Integrity vol. 2. - : Elsevier. ; , s. 2667-2673
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Konferensbidrag (refereegranskat)abstract
- When subjected to periodic loading, elastic systems containing contact interfaces might exhibit frictional slip which ceases after some loading cycles. In such cases, it is said that the system shakes down. For elastic discrete systems presenting complete contacts, it has been proved that Melan’s theorem, originally proposed for elastic-plastic problems, offers a sufficient condition for the system to shake down, provided that the contact is of an uncoupled type. In the present paper, the application of Melan’s theorem is speculated for systems involving plasticity and friction. A finite element example of an elastic-plastic solid containing a frictional crack is discussed.
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