Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Phd by thesis

BackgroundPrevious trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. MethodsWe randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. ResultsThe rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan–Meier event...

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Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

The return of a forgotten polymer—Polycaprolactone in the 21st century

Classical experiments performed half a century ago demonstrated the immense self-organizing capacity of vertebrate cells. Even after complete dissociation, cells can reaggregate and reconstruct the original architecture of an organ. More recently, this outstanding feature was used to rebuild organ parts or even complete organs from tissue or embryonic stem cells. Such stem cell-derived three-dimensional cultures are called organoids. Because organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies. Here, we summarize this rapidly evolving field and outline the potential of organoid technology for future biomedical research.

http://science.sciencemag.org/content/sci/345/6194/1247125.full.pdf

Organogenesis in a dish: modeling development and disease using organoid technologies.

https://repositorium.sdum.uminho.pt/bitstream/1822/14053/1/file.pdf

Natural–origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications

Laminopathies comprise a group of inherited diseases with variable clinical phenotypes, caused by mutations in the lamin A/C gene (LMNA). A prominent feature in several of these diseases is muscle wasting, as seen in Emery-Dreifuss muscle dystrophy, dilated cardiomyopathy and limb-girdle muscular dystrophy. Although the mechanisms underlying this phenotype remain largely obscure, two major working hypotheses are currently being investigated, namely, defects in gene regulation and/or abnormalities in nuclear architecture causing cellular fragility. In this study, using a newly developed cell compression device we have tested the latter hypothesis. The device allows controlled application of mechanical load onto single living cells, with simultaneous visualization of cellular deformation and quantitation of resistance. With the device, we have compared wild-type (MEF+/+) and LMNA knockout (MEF-/-) mouse embryonic fibroblasts (MEFs), and found that MEF-/- cells show a significantly decreased mechanical stiffness and a significantly lower bursting force. Partial rescue of the phenotype by transfection with either lamin A or lamin C prevented gross nuclear disruption, as seen in MEF-/- cells, but was unable to fully restore mechanical stiffness in these cells. Our studies show a direct correlation between absence of LMNA proteins and nuclear fragility in living cells. Simultaneous recordings by confocal microscopy revealed that the nuclei in MEF-/- cells, in contrast to MEF+/+ cells, exhibited an isotropic deformation upon indentation, despite an anisotropic deformation of the cell as a whole. This nuclear behaviour is indicative for a loss of interaction of the disturbed nucleus with the surrounding cytoskeleton. In addition, careful investigation of the three-dimensional organization of actin-, vimentin- and tubulin-based filaments showed a disturbed interaction of these structures in MEF-/- cells. Therefore, we suggest that in addition to the loss of nuclear stiffness, the loss of a physical interaction between nuclear structures (i.e. lamins) and the cytoskeleton is causing more general cellular weakness and emphasizes a potential key function for lamins in maintaining cellular tensegrity.

http://www.mate.tue.nl/mate/pdfs/4508.pdf

Decreased mechanical stiffness in LMNA−/− cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies

The progress made during the past decade in the application of mixed finite element methods to solve viscoelastic flow problems using differential constitutive equations is reviewed. The algorithmic developments are discussed in detail. Starting with the classical mixed formulation, the elastic viscous stress splitting (EVSS) method as well as the related discrete EVSS and the so-called EVSS-G method are discussed among others. Furthermore, stabilization techniques such as the streamline upwind Petrov‐Galerkin (SUPG) and the discontinuous Galerkin (DG) are reviewed. The performance of the numerical schemes for both smooth and non-smooth benchmark problems is discussed. Finally, the capabilities of viscoelastic flow solvers to predict experimental observations are reviewed. # 1998 Elsevier Science B.V. All rights reserved.

http://www.mate.tue.nl/~hulsen/cr/Baaijens1998.pdf

Mixed finite element methods for viscoelastic flow analysis : a review

A new method for the computational analysis of fluid-structure interaction of a Newtonian fluid with slender bodies is developed. It combines ideas of the fictitious domain and the mortar element method by imposing continuity of the velocity field along an interface by means of Lagrange multipliers. The key advantage of the method is that it circumvents the need for complicated mesh movement strategies common in arbitrary Lagrangian-Eulerian (ALE) methods, usually used for this purpose

A fictitious domain/mortar element method for fluid-structure interaction

Nonlocal implicit gradient-enhanced elasto-plasticity for the modelling of softening behaviour

The Pom‐Pom model, recently introduced by McLeish and Larson @J. Rheol. 42, 81‐110~1998!#, is a breakthrough in the field of viscoelastic constitutive equations. With this model, a correct nonlinear behavior in both elongation and shear is accomplished. The original differential equations, improved with local branch-point displacement, are modified to overcome three drawbacks: solutions in steady state elongation show discontinuities, the equation for orientation is unbounded for high strain rates, the model does not have a second normal stress difference in shear. The modified extended Pom‐Pom model does not show the three problems and is easy for implementation in finite element packages, because it is written as a single equation. Quantitative agreement is shown with experimental data in uniaxial, planar, equibiaxial elongation as well as shear, reversed flow and step-strain for two commercial low density polyethylene ~LDPE! melts and one high density polyethylene ~HDPE! melt. Such a good agreement over a full range of well defined rheometric experiments, i.e., shear, including reversed flow for one LDPE melt, and different elongational flows, is exceptional. © 2001 The Society of Rheology. @DOI: 10.1122/1.1380426#

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Frank P. T. Baaijens

Papers

Decreased mechanical stiffness in LMNA−/− cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies

Mixed finite element methods for viscoelastic flow analysis : a review

A fictitious domain/mortar element method for fluid-structure interaction

Nonlocal implicit gradient-enhanced elasto-plasticity for the modelling of softening behaviour

Differential constitutive equations for polymer melts: The extended Pom–Pom model