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- Bader, Erik, et al.
(author)
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Identification of proliferative and mature beta-cells in the islets of Langerhans
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 535:7612, s. 430-
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Journal article (peer-reviewed)abstract
- Insulin-dependent diabetes is a complex multifactorial disorder characterized by loss or dysfunction of beta-cells. Pancreatic beta-cells differ in size, glucose responsiveness, insulin secretion and precursor cell potential(1-5); understanding the mechanisms that underlie this functional heterogeneity might make it possible to develop new regenerative approaches. Here we show that Fltp (also known as Flattop and Cfap126), a Wnt/planar cell polarity (PCP) effector and reporter gene(6), acts as a marker gene that subdivides endocrine cells into two subpopulations and distinguishes proliferation-competent from mature beta-cells with distinct molecular, physiological and ultrastructural features. Genetic lineage tracing revealed that endocrine subpopulations from Fltp-negative and -positive lineages react differently to physiological and pathological changes. The expression of Fltp increases when endocrine cells cluster together to form polarized and mature 3D islet mini-organs(7-9). We show that 3D architecture and Wnt/PCP ligands are sufficient to trigger beta-cell maturation. By contrast, the Wnt/PCP effector Fltp is not necessary for beta-cell development, proliferation or maturation. We conclude that 3D architecture and Wnt/PCP signalling underlie functional beta-cell heterogeneity and induce beta-cell maturation. The identification of Fltp as a marker for endocrine subpopulations sheds light on the molecular underpinnings of islet cell heterogeneity and plasticity and might enable targeting of endocrine subpopulations for the regeneration of functional beta-cell mass in diabetic patients.
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- Bader, Thomas K., 1980-, et al.
(author)
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Dowel deformations in multi-dowel LVL-connections under moment loading
- 2015
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In: Wood Material Science & Engineering. - : Taylor & Francis. - 1748-0272 .- 1748-0280. ; 10:3, s. 216-231
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Journal article (peer-reviewed)abstract
- The aim of the experimental study presented herein is the assessment and quantification of the behavior of individual dowels in multi-dowel connections loaded by a bending moment. For this purpose, double-shear, steel-to-timber connections with nine steel dowels arranged in different patterns and with different dowel diameters were tested in four-point bending. In order to achieve a ductile behavior with up to 7° relative rotation, the connections were partly reinforced with self-tapping screws. The reinforcement did not influence the global load–deformation behavior, neither for dowel diameters of 12 mm nor for 20 mm, as long as cracking was not decisive. The deformation of the individual dowels was studied by means of a non-contact deformation measurement system. Thus, the crushing deformation, that is, the deformation at the steel plate, and the bending deformation of the dowels could be quantified. In the case of 12 mm dowels, the bending deformation was larger than the crushing deformation, while it was smaller in the case of 20 mm dowels. Moreover, dowels loaded parallel to the grain showed larger bending deformations than dowels loaded perpendicular to the grain. This indicates that the loading of the individual dowels in the connection differs depending on their location.
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- Bader, Thomas K., 1980-, et al.
(author)
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Experimental Assessment of the Load Distribution in Multi-Dowel Timber Connections
- 2016
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In: 17th International Conference on Experimental Mechanics, Rhodes, Greece, July 3-7, 2016.
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Conference paper (other academic/artistic)abstract
- An integrative, hierarchically organized testing procedure for the quantification of the load distribution in multi-dowel timber connections is presented herein. The use of contactless deformation measurement systems allowed the combination of test data from single dowel and multi-dowel connections, which gave access to the loads acting on each dowel over the full loading history. As a consequence of the anisotropic material behavior of wood, a nonuniform and progressively changing load distribution among the dowels was found.
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- Bader, Thomas K., 1980-, et al.
(author)
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Experimental characterization of the global and local behavior of multi-dowel LVL-connections under complex loading
- 2016
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In: Materials and Structures. - : Springer Science and Business Media LLC. - 1359-5997 .- 1871-6873. ; 49:6, s. 2407-2424
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Journal article (peer-reviewed)abstract
- The thorough experimental characterization of a dowel-type connection under various combinations of bending moments and normal forces is presented in this study. Double-shear steel-to-timber connections with 12 and 20 mm steel dowels were tested in a 4-point bending test set-up. The load, between the connected steel and wood beams, was transferred by the dowels themselves and also via an additional (passive) contact device, which introduced an eccentric normal force in the timber beam. The behavior of the connections was studied at the global scale of the connection and at the local scale of the individual dowels. A non-contact deformation measurement system was used to assess the changes of the location of the center of relative rotation over the entire loading. At the same time, the head deformations of the individual dowels could be measured, giving a direct indication about the force distribution among the dowels. Due to reinforcement, connections behaved distinctly ductile with a global relative rotation of up to 3°. Pre-stressing of the contact device by a force of 40 kN yielded an even stiffer behavior. For the particular configurations tested herein, the center of rotation was found to be close to the vertical axis of symmetry of the joint and close to the top row of the dowels. Moreover, the superimposed vertical shift of the center of relative rotation in case of a delayed normal force could be quantified. © 2015 RILEM
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- Bader, Thomas K., et al.
(author)
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Integrative experimental characterization and engineering modeling of single-dowel connections in LVL
- 2016
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618 .- 1879-0526. ; 107, s. 235-246
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Journal article (peer-reviewed)abstract
- In order to be able to realistically and consistently elucidate and subsequently simulate the load displacement behavior of single-dowel connections, the material behavior of the individual components, namely steel dowels and wood, needs to be investigated. The behavior of slotted-in, single-dowel steel-to-laminated veneer lumber (LVL) connections with dowel diameters of 12 and 20 mm is thoroughly discussed here in relation to steel dowel and LVL properties. In addition to connection tests at different load-to-grain directions of 0, 45 and 90, the corresponding embedment behavior of LVL was tested up to dowel displacements of three times the dowel diameter. The material behavior of steel dowels was studied by means of tensile and 3-point bending tests and accompanying finite element simulations. A pronounced nonlinear behavior of the single-dowel connections was observed for all load-to-grain directions. In case of loading perpendicular to the grain, a significant hardening behavior was obvious. Due to the anisotropic material properties of wood, enforcing a loading direction of 45 to the grain resulted in an additional force perpendicular to the load direction which was quantified in a novel biaxial test setup. Thus, a comprehensive and consistent database over different scales of observations of dowel connections could be established, which subsequently was exploited by means of engineering modeling. The comparison of experimental and numerical data illustrates the potential of the engineering modeling approach to overcome drawbacks of current design regulations, which are unable to appropriately predict stiffness properties of dowel connections. Moreover, the quasi-elastic limit of dowel connections was calculated and discussed by means of the model. (c) 2016 Elsevier Ltd. All rights reserved.
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