This paper presents an approach of the force/position hybrid control for a hexa parallel robot to guarantee a safe and accurate interaction when touching the object surface. A double-loop PID controller is proposed to replace the common PID controller in the position control to eliminate position errors due to the dynamics coupling effect between the arms and the vibration of the mechanical system. An impedance control model is used to guarantee a safe and accurate interaction when touching the object surface. In addition, a gradient descent iterative learning control algorithm is used and modified to determine the optimal impedance parameters in unknown environments. A model of the robot is built in SimMechanics to simulate and estimate system parameters. After that, the experimental work was conducted on a real robot to verify the effectiveness and feasibility of the proposed method. INDEX TERMS Hybrid control, Hexa robot, impedance control, double-loop PID, iterative learning.
Background Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure. Results In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway. Conclusions These findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.
Cancer cells consistently utilize the unfolded protein response (UPR) to encounter the abnormal endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins. Extreme activation of the UPR could also provoke maladaptive cell death. Previous reports have shown that NRF2 antioxidant signaling is activated by UPR and serves as noncanonical pathway to defense and reduce excessive ROS levels during ER stress. However, the mechanisms of regulating NRF2 signaling upon ER stress in glioblastoma have not been fully elucidated. Here we identify that SMURF1 protects against ER stress and facilitates glioblastoma cell survival by rewiring KEAP1-NRF2 pathway. We show that ER stress induces SMURF1 degradation. Knockdown of SMURF1 upregulates IRE1 and PERK signaling in the UPR pathway and prevents ER-associated protein degradation (ERAD) activity, leading to cell apoptosis. Importantly, SMURF1 overexpression activates NRF2 signaling to reduce ROS levels and alleviate UPR-mediated cell death. Mechanistically, SMURF1 interacts with and ubiquitinates KEAP1 for its degradation (NRF2 negative regulator), resulting in NRF2 nuclear import. Moreover, SMURF1 loss reduces glioblastoma cell proliferation and growth in subcutaneously implanted nude mice xenografts. Taken together, SMURF1 rewires KEAP1-NRF2 pathway to confer resistance to ER stress inducers and protect glioblastoma cell survival. ER stress and SMURF1 modulation may provide promising therapeutic targets for the treatment of glioblastoma.
The shape of the humanoid robot is one of the best shapes of remotely controlled robots. However, there are only a few investigations on humanoid teleoperation. In this paper, firstly, a remote cockpit and teleoperation strategy for the humanoid robot (BHR-01) are proposed. Then, we focused on the manipulation and the design of the master arm and hand. The designed master arm and hand has the following three characteristics: a) similar mechanism with human, b) the upper arm and forearm with adjustable length, c) the gravity compensation to hold on some postures. Finally, an experiment that an operator manipulated BHR-01 tracking and grasping an object is provided.
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