Course InSight: An Application of Natural Language Processing in a Course Browser

Course inSight integrates a course catalog with natural language processing and cloud database to provide recommendations based on the concepts extracted from a given course, revealing meaningful connections between courses that are not available through existing technologies. This paper justifies the rationale behind the project, narrates the design process, and discusses implementation details and possible improvements

Shift boundary material pointmethod: an image-to-simulation workflow for solids of complex geometries undergoing large deformation

We introduce a mathematical framework designed to enable a simple image-to-simulation workflow for solids of complex geometries in the geometrically nonlinear regime. While the material point method is used to circumvent the mesh distortion issues commonly exhibited in Lagrangian meshes, a shifted domain technique originated fromMain and Scovazzi (J Comput Phys 372:972–995, 2018) is used to represent the boundary conditions implicitly via a level set or signed distance function. Consequently, this method completely bypasses the need to generate high-quality conformal mesh to represent complex geometries and therefore allows modelers to select the space of the interpolation function without the constraints due to the geometric need. This important simplification enables us to simulate deformation of complex geometries inferred from voxel images. Verification examples on deformable body subjected to finite rotation have shown that the new shifted domain material point method is able to generate frame-indifferent results. Meanwhile, simulations using micro-CT images of a Hostun sand have demonstrated that this method is able to reproduce the quasi-brittle damage mechanisms of single grain without the excessively concentrated nodes commonly displayed in conformal meshes that represent 3D objects with local fine details

Different Amyloid-β Self-Assemblies Have Distinct Effects on Intracellular Tau Aggregation.

Alzheimer's disease (AD) pathology is characterized by the aggregation of beta-amyloid (Aβ) and tau in the form of amyloid plaques and neurofibrillary tangles in the brain. It has been found that a synergistic relationship between these two proteins may contribute to their roles in disease progression. However, how Aβ and tau interact has not been fully characterized. Here, we analyze how tau seeding or aggregation is influenced by different Aβ self-assemblies (fibrils and oligomers). Our cellular assays utilizing tau biosensor cells show that transduction of Aβ oligomers into the cells greatly enhances seeded tau aggregation in a concentration-dependent manner. In contrast, transduced Aβ fibrils slightly reduce tau seeding while untransduced Aβ fibrils promote it. We also observe that the transduction of α-synuclein fibrils, another amyloid protein, has no effect on tau seeding. The enhancement of tau seeding by Aβ oligomers was confirmed using tau fibril seeds derived from both recombinant tau and PS19 mouse brain extracts containing human tau. Our findings highlight the importance of considering the specific form and cellular location of Aβ self-assembly when studying the relationship between Aβ and tau in future AD therapeutic development

Structures of fibrils formed by α-synuclein hereditary disease mutant H50Q reveal new polymorphs.

Deposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, with hereditary mutations in α-synuclein linked to the first two of these conditions. Seeing the changes to the structures of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two previously unobserved polymorphs of α-synuclein: narrow and wide fibrils, formed from either one or two protofilaments, respectively. These structures recapitulate conserved features of the wild-type fold but reveal new structural elements, including a previously unobserved hydrogen-bond network and surprising new protofilament arrangements. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells and greater cytotoxicity that we observe for H50Q compared to wild-type α-synuclein

DP-MPM: Domain partitioning material point method for evolving multi-body thermal–mechanical contacts during dynamic fracture and fragmentation

We propose a material point method (MPM) to model the evolving multi-body contacts due to crack growth and fragmentation of thermo-elastic bodies. By representing particle interface with an implicit function, we adopt the gradient partition techniques introduced by Homel and Herbold (2017) to identify the separation between a pair of distinct material surfaces. This treatment allows us to replicate the frictional heating of the evolving interfaces and predict the energy dissipation more precisely in the fragmentation process. By storing the temperature at material points, the resultant MPM model captures the thermal advection–diffusion in a Lagrangian frame during the fragmentation, which in return affects the structural heating and dissipation across the frictional interfaces. The resultant model is capable of replicating the crack growth and fragmentation without requiring dynamic adaptation of data structures or insertion of interface elements. A staggered algorithm is adopted to integrate the displacement and temperature sequentially. Numerical experiments are employed to validate the diffusion between the thermal contact, the multi-body contact interactions and demonstrate how these thermo-mechanical processes affect the path-dependent behaviors of the multi-body systems