Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.

This paper introduces a procedure in the field of computational contact mechanics to analyze contact dynamics of beams undergoing large overall motion with large deformations and in self-contact situations. The presented contact procedure consists of a contact search algorithm which is employed with two approaches to impose contact constraint. The contact search task aims to detect the contact events and to identify the contact point candidates that is accomplished using an algorithm based on intersection of the oriented bounding boxes (OBBs). To impose the contact constraint, an approach based on the complementarity problem (CP) is introduced in the context of beam-to-beam contact. The other approach to enforce the contact constraint in this work is the penalty method, which is often used in the finite element and multibody literature. The latter contact force model is compared against the frictionless variant of the complementarity problem approach, linear complementarity problem approach (LCP). In the considered approaches, the absolute nodal coordinate formulation (ANCF) is used as an underlying finite element method for modeling beam-like structures in multibody applications, in particular. The employed penalty method makes use of an internal iteration scheme based on the Newton solver to fulfill the criteria for minimal penetration. Numerical examples in the case of flexible beams demonstrate the applicability of the introduced approach in a situation where a variety of contact types occur. It was found that the employed contact detection method is sufficiently accurate when paired with the studied contact constraint imposition models in simulation of the contact dynamics problems. It is further shown that the optimization-based complementarity problem approach is computationally more economical than the classical penalty method in the case of studied 2D-problems.

No abstract

No abstract

No abstract

A line-to-line beam contact formulation in the framework of the absolute nodal coordinate formulation (ANCF) is introduced in this paper. Higher- and lower-order ANCF beam elements employ the introduced beam contact formulation. The higher- and lower-order ANCF beam elements are compared in terms of their accuracy and performance in a large deformation contact problem. Efficiency of numerical integration of contact energy variation contribution to the system’s equations of motion is studied. The contacting elements’ surfaces of the ANCF beam elements are parameterized by segmentation of integration over the contact patch. Numerical results investigate the accuracy, robustness and efficiency of the developed line-to-line contact formulation by comparing against a solid element type using commercial finite element code. According to the numerical results, the higher-order ANCF beam element’s solution is closer than the lower-order ANCF beam element’s in accordance with the reference solution provided by a solid element type using commercial finite element code ABAQUS. Furthermore, the higher-order beam element is found to be more efficient than the lower-order beam with respect to the numerical integration of the contact energy variation. Expectedly, the higher-order ANCF beam element is able to capture the cross-section deformation in a large deformation contact problem, while the lower-order element fails to exhibit such cross-sectional deformation.

No abstract

No abstract