Search

Redundancy in the constrained mechanical systems often occurs in complex multibody mechanic systems in the existence of excessive constraints and singular positions due to system motion. In this work, Gauss principle of least constraint (GPLC) is applied to solve the dynamic motion of system with redundant constraints without changing the physics of system. Furthermore, the particle swarm optimization method is used to handle the minimization optimization problem. Eventually, the effectiveness of GPLC is validated through the dynamic modelling and simulation of two numerical examples (a planar four-bar mechanism and a spatial parallelogram mechanism). The simulation results are analyzed and compared with those obtained from Udwaia-Phohomsiri formulation and augmented Lagrangian formulation, in terms of constraint violation, computational efficiency and variation of the mechanical energy. From the viewpoint of computational efficiency and accuracy, GPLC can be regarded as a practical real-time simulation method for multibody systems with redundant constraints.

Gliomas are the most common and lethal tumor of the central nervous system (CNS). At present, standard treatment involves chemotherapy and radiotherapy after surgery, but the prognosis for most gliomas remains poor due to tumor heterogeneity and drug resistance. Microtubule-associated protein 2 (MAP2), a microtubule-stabilizing protein, plays a critical role in many cellular processes and may correlate with the proliferation, apoptosis, and drug sensitivity of tumor cells, especially their sensitivity to microtubule-targeting drugs (MTDs). In this study, we investigated the role of MAP2 in gliomas and its relationship to the chemosensitivity of vincristine (VCR), an MTD commonly used in glioma chemotherapy. We downregulated MAP2 expression in glioma cells using RNA interference, observed the resultant changes in the biological characteristics of the cells, and tested their drug sensitivity to VCR by MTT assay. The results show downregulation of MAP2 in glioma cells significantly inhibited cell viability and migration, induced apoptosis, and increased sensitivity to VCR in vitro. Our findings suggest that MAP2 may be a useful molecular marker in MTD chemotherapy and a potential therapeutic target in gliomas.

Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control.

In the simulation process for multi-body systems, the generated redundant constraints will result in ill-conditioned dynamic equations, which are not good for stable simulations when the system motion proceeds near a singular configuration. In order to overcome the singularity problems, the paper presents a regularization method with an explicit expression based on Gauss principle, which does not need to eliminate the constraint violation after each iteration step compared with the traditional methods. Then the effectiveness and stability are demonstrated through two numerical examples, a slider-crank mechanism and a planar four-bar linkage. Simulation results obtained with the proposed method are analyzed and compared with augmented Lagrangian formulation and the null space formulation in terms of constraints violation, drift mechanical energy and computational efficiency, which shows that the proposed method is suitable to perform efficient and stable dynamic simulations for multi-body systems with singular configurations.