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This paper presents a two-loop control framework for robotic manipulator systems subject to state constraints and input saturation, which effectively integrates planning and control strategies. Namely, a stability controller is designed in the inner loop to address uncertainties and nonlinearities; an optimization-based generator is constructed in the outer loop to ensure that state and input constraints are obeyed while concurrently minimizing the convergence time. Furthermore, to dramatically the computational burden, the optimization-based generator in the outer loop is switched to a direct model-based generator when the tracking errors are sufficiently small. In this way, both a high tracking accuracy and fast dynamic response are obtained for constrained robotic manipulator systems with considerably lower computational burden. The superiority and effectiveness of the proposed structure are illustrated through comparative simulations and experiments. • A general and systematic constrained control scheme for robotic manipulators. • Nonlinearities, uncertainties, state and input constraints are considered. • Adaptive robust controller is designed for high tracking accuracy. • Optimization-based generator is designed for fast dynamic response. • Experiments on Franka robotic manipulator reveal the effectiveness. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380). SYHA1813 exerts anti-tumor effects by simultaneously inhibiting angiogenesis and affecting tumor-associated macrophages, and shows the therapeutic potential of glioma by efficiently crossing the blood–brain barrier. [Display omitted] [ABSTRACT FROM AUTHOR]