A multigrid method for steady Euler equations on unstructured adaptive grids

A flux-difference splitting type algorithm is formulated for the steady Euler equations on unstructured grids. The polynomial flux-difference splitting technique is used. A vertex-centered finite volume method is employed on a triangular mesh. The multigrid method is in defect-correction form. A relaxation procedure with a first order accurate inner iteration and a second-order correction performed only on the finest grid, is used. A multi-stage Jacobi relaxation method is employed as a smoother. Since the grid is unstructured a Jacobi type is chosen. The multi-staging is necessary to provide sufficient smoothing properties. The domain is discretized using a Delaunay triangular mesh generator. Three grids with more or less uniform distribution of nodes but with different resolution are generated by successive refinement of the coarsest grid. Nodes of coarser grids appear in the finer grids. The multigrid method is started on these grids. As soon as the residual drops below a threshold value, an adaptive refinement is started. The solution on the adaptively refined grid is accelerated by a multigrid procedure. The coarser multigrid grids are generated by successive coarsening through point removement. The adaption cycle is repeated a few times. Results are given for the transonic flow over a NACA-0012 airfoil

Molecular Mechanisms of C9ORF72-linked Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two devastating neurological disorders that share clinical, genetic and pathological overlap. The discovery of a hexanucleotide G4C2 repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene as a major cause of FTD and ALS confirmed the genetic link between these two neurodegenerative diseases, collectively referred to as C9FTD/ALS. Many different hypotheses about the possible pathogenic mechanisms of this repeat have been proposed, including haploinsufficiency leading to partial loss of function of the endogenous C9ORF72 protein product, RNA toxicity caused by RNA molecules or RNA foci that bind and sequester RNA-binding proteins or production of toxic dipeptide repeat proteins (DPR) by repeat-associated non-AUG initiated (RAN) translation of the repeat. In this thesis, we study RNA and DPR gain-of toxicity in vitro and in vivo models (zebrafish and mouse). We also characterize HR23B pathology in post-mortem brain sections of C9FTD/ALS patients. Our data mainly supports DPR toxicity. Identification of the pathological pathways underlying neurodegeneration could guide future research and lead to new treatments and is therefore of great importance for the FTD/ALS field

Simulation of fluid-structure interaction with the interface artificial compressibility method

Partitioned fluid–structure interaction simulations of the arterial system are difficult due to the incompressibility of the fluid and the shape of the domain. The interface artificial compressibility (IAC) method mitigates the incompressibility constraint by adding a source term to the continuity equation in the fluid domain adjacent to the fluid–structure interface. This source term imitates the effect of the structure's displacement as a result of the fluid pressure and disappears when the coupling iterations have converged. The IAC method requires a small modification of the flow solver but not of the black-box structural solver and it outperforms a partitioned quasi-Newton coupling of the two black-box solvers in a simulation of a carotid bifurcation. Copyright © 2009 John Wiley & Sons, Ltd

Inducible expression of human C9ORF72 36× G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice

The hexanucleotide G4C2 repeat expansion in the first intron of the C9ORF72 gene accounts for the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs), which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion, and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the human C9ORF72 repeat and/ or DPRs show variable pathological, functional and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36× pure G4C2 repeats with 100-bp upstream and downstream human flanking regions. Brain-specific expression causes the formation of sporadic sense DPRs aggregates upon 6 months of dox induction, but no apparent neurodegeneration. Expression in the rest of the body evokes abundant sense DPRs in multiple organs, leading to weight loss, neuromuscular junction disruption, myopathy and a locomotor phenotype within the time frame of 4 weeks. We did not observe any RNA foci or pTDP-43 pathology. Accumulation of DPRs and the myopathy phenotype could be prevented when 36× G4C2 repeat expression was stopped after 1 week. After 2 weeks of expression, the phenotype could not be reversed, even though DPR levels were reduced. In conclusion, expression of 36× pure G4C2 repeats including 100-bp human flanking regions is sufficient for RAN translation of sense DPRs, and evokes a functional locomotor phenotype. Our inducible mouse model suggests that early diagnosis and treatment are important for C9FTD/ALS patients