Engineering multi-functional protein biologics through PAL-mediated hydrazide ligation

Attributed to the -effects, hydrazides are nucleophilic despite being non-basic. Herein, we report that the hydrazide nucleophiles are effective acyl acceptors in the ligation reactions catalyzed by peptidyl asparaginyl ligases (PALs). Because hydrazides are easily functionalizable, hydrazide ligation is highly versatile. Interestingly, the linkages formed with the hydrazide substrates have varying degrees of liability toward the PAL enzyme, with some being remarkably resistant and thus ensuring nearly irreversible ligation. Using the hydrazide ligation method, we labelled an EGFR-targeting affibody-Fc fusion protein with various functional moieties to generate selective and potent cancer-imaging and therapeutic agents. Irreversible hydrazide ligation also allowed a sequential ligation scheme to be conducted on a protein. Using this scheme, quadruple FITC labels were introduced onto the N- and C-termini of the affibody-Fc protein to yield a bi-specific engager for Car-NK cell therapy. Our work expands the substrate scope of PAL enzymes and further point to their promise as a precision manufacturing tool for multi-functional protein biologics.

A Graph Theory-Based Method for Dynamic Modeling and Parameter Identification of 6-DOF Industrial Robots

At present, the absolute positioning accuracy and control accuracy of industrial serial robots need to be improved to meet the accuracy requirements of precision manufacturing and precise control. An accurate dynamic model is an important theoretical basis for solving this problem, and precise dynamic parameters are the prerequisite for precise control. The research of dynamics and parameter identification can greatly promote the application of robots in the field of precision manufacturing and automation. In this paper, we study the dynamical modeling and dynamic parameter identification of an industrial robot system with six rotational DOF (6R robot system) and propose a new method for identifying dynamic parameters. Our aim is to provide an accurate mathematical description of the dynamics of the 6R robot and to accurately identify its dynamic parameters. First, we establish an unconstrained dynamic model for the 6R robot system and rewrite it to obtain the dynamic parameter identification model. Second, we establish the constraint equations of the 6R robot system. Finally, we establish the dynamic model of the constrained 6R robot system. Through the ADAMS simulation experiment, we verify the correctness and accuracy of the dynamic model. The experiments prove that the result of parameter identification has extremely high accuracy and the dynamic model can accurately describe the 6R robot system mathematically. The dynamic modeling method proposed in this paper can be used as the theoretical basis for the study of 6R robot system dynamics and the study of dynamics-based control theory.

Research on Surface Quality by Ultrasonic Vibration-Assisted Face Grinding of Cemented Carbide

Cemented carbide has huge applications in industrial production, but its high mechanical properties also increase the difficulty of processing. In this work, ultrasonic vibration-assisted grinding technology is used for the precision manufacturing of cemented carbide. The influence of the dynamic trajectory of the grains on the material removal process is analyzed. The morphology and roughness of the processed surface are measured and studied. It was observed that in the conventional grinding, the blade pattern is obvious with some defects on the surface. While in the ultrasonic vibration-assisted grinding, the material surface is mainly distributed with pits and small protrusions, and there is no obvious blade pattern. According to the roughness test, the roughness of ultrasonic vibration-assisted grinding is better than that of conventional grinding, and the increase in amplitude has a significant effect on the improvement of roughness. When the amplitude increases from 3μm to 9μm, the surface roughness is improved about 38.1%. The research of ultrasonic vibration-assisted grinding should be of great importance for promote the high-efficiency and high-quality processing and special applications of cemented carbide.