In the current practice of multi-axis machining of freeform surfaces, the interface surface between the roughing and finishing process is simply an offset surface of the nominal surface. While there have already been ...In the current practice of multi-axis machining of freeform surfaces, the interface surface between the roughing and finishing process is simply an offset surface of the nominal surface. While there have already been attempts at minimizing the machining time by considering the kinematic capacities of the machine tool and/or the physical constraints such as the cutting force, they all target independently at either the finishing or the roughing process alone and are based on the simple premise of an offset interface surface. Conceivably, since the total machining time should count that of both roughing and finishing process and both of them crucially depend on the interface surface, it is natural to ask if, under the same kinematic capacities and the same physical constraints, there is a nontrivial interface surface whose corresponding total machining time will be the minimum among all the possible（infinite） choices of interface surfaces, and this is the motivation behind the work of this paper. Specifically, with respect to the specific type of iso-planar milling for both roughing and finishing, we present a practical algorithm for determining such an optimal interface surface for an arbitrary freeform surface. While the algorithm is proposed for iso-planar milling, it can be easily adapted to other types of milling strategy such as contour milling. Both computer simulation and physical cutting experiments of the proposed method have convincingly demonstrated its advantages over the traditional simple offset method.展开更多
Thermotherapy and chemotherapy have received extensive attention to tumor treatment. However, thermal tolerance and drug resistance severely limit clinical effect of tumor therapy owing to endoplasmic reticulum(ER) st...Thermotherapy and chemotherapy have received extensive attention to tumor treatment. However, thermal tolerance and drug resistance severely limit clinical effect of tumor therapy owing to endoplasmic reticulum(ER) stress. Reducing thermal tolerance and drug resistance of tumors is an urgent challenge to be solved. In this work, we design a nanoplatform of PBA-Dtxl@MIL-101 as an ER inhibitor. Amino functionalized Fe-metal organic framework(MIL-101) nanoparticles are synthesized as p H and microwave(MW) dual stimuli-responsive drug delivery system. Then, the chemical chaperones of 4-phenylbutyric acid(PBA) and antineoplastic drug Docetaxel(Dtxl) were successfully loaded into MIL-101 nanoparticles to form PBA-Dtxl@MIL-101 nanoparticles. Furthermore, PBA-Dtxl@MIL-101 nanoparticles exhibit inhibitor effect of ER stress through upregulating caspase 9 proteins and reduce thermal tolerance by downregulating HSP 90. It was demonstrated that the therapy sensitized by PBA-Dtxl@MIL-101 nanoparticles obviously destroyed tumor cells, showing simultaneously enhanced thermo-chemo therapy.展开更多
文摘In the current practice of multi-axis machining of freeform surfaces, the interface surface between the roughing and finishing process is simply an offset surface of the nominal surface. While there have already been attempts at minimizing the machining time by considering the kinematic capacities of the machine tool and/or the physical constraints such as the cutting force, they all target independently at either the finishing or the roughing process alone and are based on the simple premise of an offset interface surface. Conceivably, since the total machining time should count that of both roughing and finishing process and both of them crucially depend on the interface surface, it is natural to ask if, under the same kinematic capacities and the same physical constraints, there is a nontrivial interface surface whose corresponding total machining time will be the minimum among all the possible（infinite） choices of interface surfaces, and this is the motivation behind the work of this paper. Specifically, with respect to the specific type of iso-planar milling for both roughing and finishing, we present a practical algorithm for determining such an optimal interface surface for an arbitrary freeform surface. While the algorithm is proposed for iso-planar milling, it can be easily adapted to other types of milling strategy such as contour milling. Both computer simulation and physical cutting experiments of the proposed method have convincingly demonstrated its advantages over the traditional simple offset method.
基金financial support from the Beijing Natural Science Foundation (No. 2202057)Sichuan Science and Technology Program (No. 2020YFSY0018)。
文摘Thermotherapy and chemotherapy have received extensive attention to tumor treatment. However, thermal tolerance and drug resistance severely limit clinical effect of tumor therapy owing to endoplasmic reticulum(ER) stress. Reducing thermal tolerance and drug resistance of tumors is an urgent challenge to be solved. In this work, we design a nanoplatform of PBA-Dtxl@MIL-101 as an ER inhibitor. Amino functionalized Fe-metal organic framework(MIL-101) nanoparticles are synthesized as p H and microwave(MW) dual stimuli-responsive drug delivery system. Then, the chemical chaperones of 4-phenylbutyric acid(PBA) and antineoplastic drug Docetaxel(Dtxl) were successfully loaded into MIL-101 nanoparticles to form PBA-Dtxl@MIL-101 nanoparticles. Furthermore, PBA-Dtxl@MIL-101 nanoparticles exhibit inhibitor effect of ER stress through upregulating caspase 9 proteins and reduce thermal tolerance by downregulating HSP 90. It was demonstrated that the therapy sensitized by PBA-Dtxl@MIL-101 nanoparticles obviously destroyed tumor cells, showing simultaneously enhanced thermo-chemo therapy.
