The finite element analysis and the optimum design of aluminum profile extrusion mould were investigated using the ANSYS software and its parameterized modeling method. The optimum dimensions of the mould were obtaine...The finite element analysis and the optimum design of aluminum profile extrusion mould were investigated using the ANSYS software and its parameterized modeling method. The optimum dimensions of the mould were obtained. It is found that the stress distribution is very uneven, and the stress convergence is rather severe in the bridge of the aluminum profile extrusion mould. The optimum height of the mould is 70.527 mm, and the optimum radius of dividing holes are 70.182 mm and 80.663 mm. Increasing the height of the mould in the range of 61.282 mm to 70.422 mm can prolong its longevity, but when the height is over 70.422 mm, its longevity reduces.展开更多
Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate vario...Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate various computational tools,including machine learning,molecular dynamic simulation and physiologically based absorption modeling(PBAM),to enhance andrographolide(AG)/cyclodextrins(CDs)formulation design.The light GBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy.AG/γ-CD inclusion complexes showed the strongest binding affinity,which was experimentally validated by the phase solubility study.The molecular dynamic simulation was used to investigate the inclusion mechanism between AG andγ-CD,which was experimentally characterized by DSC,FTIR and NMR techniques.PBAM was applied to simulate the in vivo behavior of the formulations,which were validated by cell and animal experiments.Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate(TPGS)significantly increased the intracellular uptake of AG in MDCKMDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers.The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills,respectively.In conclusion,this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility,dissolution rate and bioavailability.The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.展开更多
Thermodynamic and kinetic study on TRIP (transformation induced plasticity) steels, cemented carbides and mold steel for plastics were carried out in order to design modern advanced materials. With the sublattice mo...Thermodynamic and kinetic study on TRIP (transformation induced plasticity) steels, cemented carbides and mold steel for plastics were carried out in order to design modern advanced materials. With the sublattice model, equilibrium compositions of ferrite and austenite phases in TRIP steels, as well as volume fraction of austenite at inter-critical temperatures for different time were calculated. Concentration profiles of carbon, manganese, aluminum and silicon in the steels were also estimated in the lattice fixed frame of reference. The effect of Si and Mn on TRIP was discussed according to thermodynamic and kinetic analyses. In order to understand and produce the graded nanophase structure of cemented carbides, miscellaneous phases in the M-Co-C (M= Ti, Ta, Nh) systems and Co-V-C system were modeled. Solution parameters and thermodynamic: properties were listed in detail. The improvement of machining behavior of prehardened mould steel for plastics was obtained by computer-aided composition design. The results showed that the matrix composition of large-section prehardened mould steel for plastic markedly influences the precipitation of non-metallic inclusion and the composition control by the aid of Thermo-Calc software package minimizes the amount of detrimental oxide inclusion. In addition, the modification of calcium was optimized in composition design.展开更多
Suitable optimization and simulation were performed using a powerful software package with a mature database as well as modem measurement facilities, which led to the successful designing and manufacturing of advanced...Suitable optimization and simulation were performed using a powerful software package with a mature database as well as modem measurement facilities, which led to the successful designing and manufacturing of advanced steels. In the course of designing, the composition of a large section of prehardened mold steel for plastics was estimated so as to lower the quantities of oxide inclusions to change the type of carbides and to raise the machinability. The composition and process were adjusted to obtain satisfactory surface quality for the prevailing galvanization in transformation-induced plasticity (TRIP) steel. The refuting process of low-carbon steel was simulated in the light of both Thermo-Calc and Factsage. Thermodynamic and kinetic analyses were always conducted during the test and the procedure.展开更多
The general computer-aided design (CAD) software cannot meet the mould design requirement of the autoclave process for composites, because many parameters such as temperature and pressure should be considered in the...The general computer-aided design (CAD) software cannot meet the mould design requirement of the autoclave process for composites, because many parameters such as temperature and pressure should be considered in the mould design process, in addition to the material and geometry of the part. A framed-mould computer-aided design system (FMCAD) used in the autoclave moulding process is proposed in this paper. A function model of the software is presented, in which influence factors such as part structure, mould structure, and process parameters are considered; a design model of the software is established using object oriented (O-O) technology to integrate the stiffness calculation, temperature field calculation, and deformation field calculation of mould in the design, and in the design model, a hybrid model of mould based on calculation feature and form feature is presented to support those calculations. A prototype system is developed, in which a mould design process wizard is built to integrate the input information, calculation, analysis, data storage, display, and design results of mould design. Finally, three design examples are used to verify the prototype.展开更多
Fully human antibodies have minimal immunogenicity and safety profiles.At present,most potential antibody drugs in clinical trials are humanized or fully human.Human antibodies are mostly generated using the phage dis...Fully human antibodies have minimal immunogenicity and safety profiles.At present,most potential antibody drugs in clinical trials are humanized or fully human.Human antibodies are mostly generated using the phage display method(in vitro)or by transgenic mice(in vivo);other methods include B lymphocyte immortalization,human–human hybridoma,and single-cell polymerase chain reaction.Here,we describe a structure-based computer-aided de novo design technology for human antibody generation.Based on the complex structure of human epidermal growth factor receptor 2(HER2)/Herceptin,we first designed six short peptides targeting the potential epitope of HER2 recognized by Herceptin.Next,these peptides were set as complementarity determining regions in a suitable immunoglobulin frame,giving birth to a novel anti-HER2 antibody named "HF,"which possessed higher affinity and more effective anti-tumor activity than Herceptin.Our work offers a useful tool for the quick design and selection of novel human antibodies for basic mechanical research as well as for imaging and clinical applications in immune-related diseases,such as cancer and infectious diseases.展开更多
Custom-made esthetic finger prostheses, which are used for rehabilitation of patients with missing or impaired fingers, have been fabricated manually. However, such fabrication is time-consuming and requires manual sk...Custom-made esthetic finger prostheses, which are used for rehabilitation of patients with missing or impaired fingers, have been fabricated manually. However, such fabrication is time-consuming and requires manual skill. Here we propose a computer-aided method for fabricating finger pros-theses to save time and allow fabrications that do not require considerable manual skill. In this method, the dimensions of a patient’s healthy finger on the contralateral hand are first measured using a caliper. Using these dimensions, a three-dimensional model is constructed for fabricating a prosthesis for the patient’s impaired finger. Using the 3D model, a mold is designed using 3D modeling tools and a computer-aided design system. The resulting mold is then fabricated using a 3D printer. A finger prosthesis is fabricated by pouring silicone resin into the mold. A finger prosthesis for a volunteer was experimentally fabricated according to the proposed method. To evaluate the size and shape of the finger prosthesis, the difference between the finger prosthesis and the original finger of the volunteer was analyzed. Because the average difference between them was 0.25 mm, it was concluded that the proposed method could be used to fabricate a finger prosthesis of adequate size and shape.展开更多
The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on th...The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on the basis of shadow projections. This article provides basic information regarding CAD of X-ray microtomography and a scheme consisting of three levels. The article also shows basic relations of X-ray computed tomography, the generalized scheme of an X-ray microtomographic scanner. The methods of X-ray imaging of the spatial microstructure and morphometry of materials are described. The main characteristics of an X-ray microtomographic scanner, the X-ray source, X-ray optical elements and mechanical components of the positioning system are shown. The block scheme and software functional scheme for intelligent neural network system of analysis of the internal microstructure of objects are presented. The method of choice of design parameters of CAD of X-ray microtomography aims at improving the quality of design and reducing costs of it. It is supposed to reduce the design time and eliminate the growing number of engineers involved in development and construction of X-ray microtomographic scanners.展开更多
Transportation plays a critical role in the economic sector in Bangladesh.Since its independence,infrastructure has been developing rapidly,includ-ing land,water,and air transportation.National economy is increasing a...Transportation plays a critical role in the economic sector in Bangladesh.Since its independence,infrastructure has been developing rapidly,includ-ing land,water,and air transportation.National economy is increasing at a relatively high rate,leading to the better-off of people’s lives.As the living standards keep improving,people are more concerned about safety issues in transportation.This article makes an analysis of the status quo of traffic safety in Bangladesh and compares the Bangladeshi code with American code AASHTO from the geometric aspects of horizontal and vertical align-ment,in an effort to provide reference to the highway design in Bangla-desh.Through a reasonable design,the traffic safety will be under control and accident rate as well as economic loss will be minimized.展开更多
Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different ge...Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different geometries,and at the macro-level,the geometric design of implants will also affect the biological function of cells.In this study,three kinds of porous scaffolds with square,triangular and circle rod shapes were designed and 3D printed.This study observed the proliferation and differentiation of MC3T3-E1 cells during surface culture of the three types of scaffolds.It also evaluated the characteristics of the three scaffolds by means of compression tests and scanning electron microscopy to provide a reference for the design of porous titanium alloy implants for clinical applications.The trends of cell proliferation and gene expression between the three types of scaffolds were observed after treatment with two inhibitors.The results show that the square rod porous scaffolds have the best proliferative and osteogenic activities,and these findings may be due to differences in piezo-type mechanosensitive ion channel component 1(Piezo1)and Yes-associated protein(YAP)expression caused by the macro-geometric topography.展开更多
Colorectal cancer(CRC)is the second leading cause of cancer mortality worldwide.At initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-est...Colorectal cancer(CRC)is the second leading cause of cancer mortality worldwide.At initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor.In this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported previously.ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound.In addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound state.Furthermore,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef interaction.These results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.展开更多
Inspired by the driving muscles of the human arm,a 4-Degree of Freedom(DOF)concentrated driving humanoid robotic arm is proposed based on a spatial double parallel four-bar mechanism.The four-bar mechanism design redu...Inspired by the driving muscles of the human arm,a 4-Degree of Freedom(DOF)concentrated driving humanoid robotic arm is proposed based on a spatial double parallel four-bar mechanism.The four-bar mechanism design reduces the inertia of the elbow-driving unit and the torque by 76.65%and 57.81%,respectively.Mimicking the human pose regulation strategy that the human arm picks up a heavy object by adjusting its posture naturally without complicated control,the robotic arm features an integrated position-level closed-form inverse solution method considering both geometric and load capacity limitations.This method consists of a geometric constraint model incorporating the arm angle(φ)and the Global Configuration(GC)to avoid joint limits and singularities,and a load capacity model to constrain the feasible domain of the arm angle.Further,trajectory tracking simulations and experiments are conducted to validate the feasibility of the proposed inverse solution method.The simulated maximum output torque,maximum output power and total energy consumption of the robotic arm are reduced by up to 2.0%,13.3%,and 33.3%,respectively.The experimental results demonstrate that the robotic arm can bear heavy loads in a human-like posture,effectively reducing the maximum output torque and energy consumption of the robotic arm by 1.83%and 5.03%,respectively,while avoiding joints beyond geometric and load capacity limitations.The proposed design provides a high payload–weight ratio and an efficient pose control solution for robotic arms,which can potentially broaden the application spectrum of humanoid robots.展开更多
Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes ...Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes which are subjected to stress-induced failure.The probability of failure(POF)depends on many factors,of which the geometry of an open stope is especially important.In this study,a methodology is proposed to assess the effect of stope geometrical parameters on the POF,using numerical modelling.Different ranges for each input parameter are defined according to previous surveys on open stope geometry in a number of Canadian underground mines.A Monte-Carlo simulation technique is combined with the finite difference code FLAC3D,to generate model realizations containing stopes with different geometrical features.The probability of failure(POF)for different categories of stope geometry,is calculated by considering two modes of failure;relaxation-related gravity driven(tensile)failure and rock mass brittle failure.The individual and interactive effects of stope geometrical parameters on the POF,are analyzed using a general multi-level factorial design.Finally,mathematical optimization techniques are employed to estimate the most stable stope conditions,by determining the optimal ranges for each stope’s geometrical parameter.展开更多
The concept of′Probe detector′is introduced in this paper with its application in geometricmodeling and graphics.In terms of the concept,the authors derive edge data from the CSG datarepresentation and establish a w...The concept of′Probe detector′is introduced in this paper with its application in geometricmodeling and graphics.In terms of the concept,the authors derive edge data from the CSG datarepresentation and establish a wireframe model.展开更多
Abstract For two rational quadratic B spline curves with same control vertexes, the cross ratio of four collinear points are represented: which are any one of the vertexes, and the two points that the ray initialing f...Abstract For two rational quadratic B spline curves with same control vertexes, the cross ratio of four collinear points are represented: which are any one of the vertexes, and the two points that the ray initialing from the vertex intersects with the corresponding segments of the two curves, and the point the ray intersecting with the connecting line between the two neighboring vertexes. Different from rational quadratic Bézier curves, the value is generally related with the location of the ray, and the necessary and sufficient condition of the ratio being independent of the ray's location is showed. Also another cross ratio of the following four collinear points are suggested, i.e. one vertex, the points that the ray from the initial vertex intersects respectively with the curve segment, the line connecting the segments end points, and the line connecting the two neighboring vertexes. This cross ratio is concerned only with the ray's location, but not with the weights of the curve. Furthermore, the cross ratio is projective invariant under the projective transformation between the two segments.展开更多
文摘The finite element analysis and the optimum design of aluminum profile extrusion mould were investigated using the ANSYS software and its parameterized modeling method. The optimum dimensions of the mould were obtained. It is found that the stress distribution is very uneven, and the stress convergence is rather severe in the bridge of the aluminum profile extrusion mould. The optimum height of the mould is 70.527 mm, and the optimum radius of dividing holes are 70.182 mm and 80.663 mm. Increasing the height of the mould in the range of 61.282 mm to 70.422 mm can prolong its longevity, but when the height is over 70.422 mm, its longevity reduces.
基金financially supported by the FDCT Project 0029/2018/A1the University of Macao Research Grants(MYRG2019-00041-ICMS)performed in part at the High-Performance Computing Cluster(HPCC)which is supported by Information and Communication Technology Office(ICTO)of the University of Macao。
文摘Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists,which is time-consuming,high cost and waste materials.This research aims to integrate various computational tools,including machine learning,molecular dynamic simulation and physiologically based absorption modeling(PBAM),to enhance andrographolide(AG)/cyclodextrins(CDs)formulation design.The light GBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy.AG/γ-CD inclusion complexes showed the strongest binding affinity,which was experimentally validated by the phase solubility study.The molecular dynamic simulation was used to investigate the inclusion mechanism between AG andγ-CD,which was experimentally characterized by DSC,FTIR and NMR techniques.PBAM was applied to simulate the in vivo behavior of the formulations,which were validated by cell and animal experiments.Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate(TPGS)significantly increased the intracellular uptake of AG in MDCKMDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers.The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills,respectively.In conclusion,this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility,dissolution rate and bioavailability.The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.
文摘Thermodynamic and kinetic study on TRIP (transformation induced plasticity) steels, cemented carbides and mold steel for plastics were carried out in order to design modern advanced materials. With the sublattice model, equilibrium compositions of ferrite and austenite phases in TRIP steels, as well as volume fraction of austenite at inter-critical temperatures for different time were calculated. Concentration profiles of carbon, manganese, aluminum and silicon in the steels were also estimated in the lattice fixed frame of reference. The effect of Si and Mn on TRIP was discussed according to thermodynamic and kinetic analyses. In order to understand and produce the graded nanophase structure of cemented carbides, miscellaneous phases in the M-Co-C (M= Ti, Ta, Nh) systems and Co-V-C system were modeled. Solution parameters and thermodynamic: properties were listed in detail. The improvement of machining behavior of prehardened mould steel for plastics was obtained by computer-aided composition design. The results showed that the matrix composition of large-section prehardened mould steel for plastic markedly influences the precipitation of non-metallic inclusion and the composition control by the aid of Thermo-Calc software package minimizes the amount of detrimental oxide inclusion. In addition, the modification of calcium was optimized in composition design.
基金The study was financially supported by the key project of Science and Technology Commission of Shanghai Local Gov-ernment (No. 015211010), the National Natural Science Foundation of China (No. 50171038) and the China-Belgium bi-lateral project (No. 2001-242).
文摘Suitable optimization and simulation were performed using a powerful software package with a mature database as well as modem measurement facilities, which led to the successful designing and manufacturing of advanced steels. In the course of designing, the composition of a large section of prehardened mold steel for plastics was estimated so as to lower the quantities of oxide inclusions to change the type of carbides and to raise the machinability. The composition and process were adjusted to obtain satisfactory surface quality for the prevailing galvanization in transformation-induced plasticity (TRIP) steel. The refuting process of low-carbon steel was simulated in the light of both Thermo-Calc and Factsage. Thermodynamic and kinetic analyses were always conducted during the test and the procedure.
文摘The general computer-aided design (CAD) software cannot meet the mould design requirement of the autoclave process for composites, because many parameters such as temperature and pressure should be considered in the mould design process, in addition to the material and geometry of the part. A framed-mould computer-aided design system (FMCAD) used in the autoclave moulding process is proposed in this paper. A function model of the software is presented, in which influence factors such as part structure, mould structure, and process parameters are considered; a design model of the software is established using object oriented (O-O) technology to integrate the stiffness calculation, temperature field calculation, and deformation field calculation of mould in the design, and in the design model, a hybrid model of mould based on calculation feature and form feature is presented to support those calculations. A prototype system is developed, in which a mould design process wizard is built to integrate the input information, calculation, analysis, data storage, display, and design results of mould design. Finally, three design examples are used to verify the prototype.
基金This work was supported by grants from the National Sciences Fund(31370938 and 81272528)The Fund(81272528)offered experiment material and collected the data for analysisThe Fund(31370938)helped design the study and was helpful in preparing the manuscript.
文摘Fully human antibodies have minimal immunogenicity and safety profiles.At present,most potential antibody drugs in clinical trials are humanized or fully human.Human antibodies are mostly generated using the phage display method(in vitro)or by transgenic mice(in vivo);other methods include B lymphocyte immortalization,human–human hybridoma,and single-cell polymerase chain reaction.Here,we describe a structure-based computer-aided de novo design technology for human antibody generation.Based on the complex structure of human epidermal growth factor receptor 2(HER2)/Herceptin,we first designed six short peptides targeting the potential epitope of HER2 recognized by Herceptin.Next,these peptides were set as complementarity determining regions in a suitable immunoglobulin frame,giving birth to a novel anti-HER2 antibody named "HF,"which possessed higher affinity and more effective anti-tumor activity than Herceptin.Our work offers a useful tool for the quick design and selection of novel human antibodies for basic mechanical research as well as for imaging and clinical applications in immune-related diseases,such as cancer and infectious diseases.
文摘Custom-made esthetic finger prostheses, which are used for rehabilitation of patients with missing or impaired fingers, have been fabricated manually. However, such fabrication is time-consuming and requires manual skill. Here we propose a computer-aided method for fabricating finger pros-theses to save time and allow fabrications that do not require considerable manual skill. In this method, the dimensions of a patient’s healthy finger on the contralateral hand are first measured using a caliper. Using these dimensions, a three-dimensional model is constructed for fabricating a prosthesis for the patient’s impaired finger. Using the 3D model, a mold is designed using 3D modeling tools and a computer-aided design system. The resulting mold is then fabricated using a 3D printer. A finger prosthesis is fabricated by pouring silicone resin into the mold. A finger prosthesis for a volunteer was experimentally fabricated according to the proposed method. To evaluate the size and shape of the finger prosthesis, the difference between the finger prosthesis and the original finger of the volunteer was analyzed. Because the average difference between them was 0.25 mm, it was concluded that the proposed method could be used to fabricate a finger prosthesis of adequate size and shape.
文摘The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on the basis of shadow projections. This article provides basic information regarding CAD of X-ray microtomography and a scheme consisting of three levels. The article also shows basic relations of X-ray computed tomography, the generalized scheme of an X-ray microtomographic scanner. The methods of X-ray imaging of the spatial microstructure and morphometry of materials are described. The main characteristics of an X-ray microtomographic scanner, the X-ray source, X-ray optical elements and mechanical components of the positioning system are shown. The block scheme and software functional scheme for intelligent neural network system of analysis of the internal microstructure of objects are presented. The method of choice of design parameters of CAD of X-ray microtomography aims at improving the quality of design and reducing costs of it. It is supposed to reduce the design time and eliminate the growing number of engineers involved in development and construction of X-ray microtomographic scanners.
文摘Transportation plays a critical role in the economic sector in Bangladesh.Since its independence,infrastructure has been developing rapidly,includ-ing land,water,and air transportation.National economy is increasing at a relatively high rate,leading to the better-off of people’s lives.As the living standards keep improving,people are more concerned about safety issues in transportation.This article makes an analysis of the status quo of traffic safety in Bangladesh and compares the Bangladeshi code with American code AASHTO from the geometric aspects of horizontal and vertical align-ment,in an effort to provide reference to the highway design in Bangla-desh.Through a reasonable design,the traffic safety will be under control and accident rate as well as economic loss will be minimized.
基金This study was carried out at the 3D Printing Innovation Research Centre of the Ninth People's Hospital Affiliated to the School of Medicine of Shanghai Jiao Tong University,and the authors thank the founding support from the Shanghai Municipal Key Clinical Specialty-Biomedical Materials(shslczdzk06701)the 3-year Action Plan of Shen kang Development Centre(SHDC2020CR2019B)+2 种基金the Huangpu District Industrial Support Fund(XK2020009)the Shanghai Engineering Research Centre of Innovative Orthopedic Instruments and Personalized Medicine(19DZ2250200)the Industry Standard Study on 3D Printing Personalized Titanium Alloy Pelvic Reconstruction Prosthesis(21DZ2201500).
文摘Porous titanium alloy is currently widely used in clinical treatment of orthopaedic diseases for its lower elastic modulus and ability to integrate with bone tissue.At the micro-level,cells can respond to different geometries,and at the macro-level,the geometric design of implants will also affect the biological function of cells.In this study,three kinds of porous scaffolds with square,triangular and circle rod shapes were designed and 3D printed.This study observed the proliferation and differentiation of MC3T3-E1 cells during surface culture of the three types of scaffolds.It also evaluated the characteristics of the three scaffolds by means of compression tests and scanning electron microscopy to provide a reference for the design of porous titanium alloy implants for clinical applications.The trends of cell proliferation and gene expression between the three types of scaffolds were observed after treatment with two inhibitors.The results show that the square rod porous scaffolds have the best proliferative and osteogenic activities,and these findings may be due to differences in piezo-type mechanosensitive ion channel component 1(Piezo1)and Yes-associated protein(YAP)expression caused by the macro-geometric topography.
基金funded by the National Key R&D Program of China(2023YFF1205103 to Jian Zhang)the Key Research and Construction Programs of Ningxia Hui Autonomous Region(2022BEG01002 to Jian Zhang,China)+3 种基金the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-007 to Jian Zhang,China)the National Natural Science Foundation of China(22237005 and 81925034 to Jian Zhang)the open fund of state key laboratory of Pharmaceutical Biotechnology,Nanjing University(KF-202201 to Jian Zhang,China)the open fund of Basic Science Research Center Base(Pharmaceutical Science Y202203 to Xiuyan Yang,China).
文摘Colorectal cancer(CRC)is the second leading cause of cancer mortality worldwide.At initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging endeavor.In this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported previously.ONIOM model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental compound.In addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound state.Furthermore,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef interaction.These results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.
基金funded by the National Natural Science Foundation of China(NO.52175069).
文摘Inspired by the driving muscles of the human arm,a 4-Degree of Freedom(DOF)concentrated driving humanoid robotic arm is proposed based on a spatial double parallel four-bar mechanism.The four-bar mechanism design reduces the inertia of the elbow-driving unit and the torque by 76.65%and 57.81%,respectively.Mimicking the human pose regulation strategy that the human arm picks up a heavy object by adjusting its posture naturally without complicated control,the robotic arm features an integrated position-level closed-form inverse solution method considering both geometric and load capacity limitations.This method consists of a geometric constraint model incorporating the arm angle(φ)and the Global Configuration(GC)to avoid joint limits and singularities,and a load capacity model to constrain the feasible domain of the arm angle.Further,trajectory tracking simulations and experiments are conducted to validate the feasibility of the proposed inverse solution method.The simulated maximum output torque,maximum output power and total energy consumption of the robotic arm are reduced by up to 2.0%,13.3%,and 33.3%,respectively.The experimental results demonstrate that the robotic arm can bear heavy loads in a human-like posture,effectively reducing the maximum output torque and energy consumption of the robotic arm by 1.83%and 5.03%,respectively,while avoiding joints beyond geometric and load capacity limitations.The proposed design provides a high payload–weight ratio and an efficient pose control solution for robotic arms,which can potentially broaden the application spectrum of humanoid robots.
基金funded by a grant from Natural Sciences and Engineering Research Council of Canada (NSERC)the authors would like to acknowledge the Niobec mine (Saint-Honoré, QuébecQuébec)
文摘Stress-induced failure is among the most common causes of instability in Canadian deep underground mines.Open stoping is the most widely practiced underground excavation method in these mines,and creates large stopes which are subjected to stress-induced failure.The probability of failure(POF)depends on many factors,of which the geometry of an open stope is especially important.In this study,a methodology is proposed to assess the effect of stope geometrical parameters on the POF,using numerical modelling.Different ranges for each input parameter are defined according to previous surveys on open stope geometry in a number of Canadian underground mines.A Monte-Carlo simulation technique is combined with the finite difference code FLAC3D,to generate model realizations containing stopes with different geometrical features.The probability of failure(POF)for different categories of stope geometry,is calculated by considering two modes of failure;relaxation-related gravity driven(tensile)failure and rock mass brittle failure.The individual and interactive effects of stope geometrical parameters on the POF,are analyzed using a general multi-level factorial design.Finally,mathematical optimization techniques are employed to estimate the most stable stope conditions,by determining the optimal ranges for each stope’s geometrical parameter.
文摘The concept of′Probe detector′is introduced in this paper with its application in geometricmodeling and graphics.In terms of the concept,the authors derive edge data from the CSG datarepresentation and establish a wireframe model.
文摘Abstract For two rational quadratic B spline curves with same control vertexes, the cross ratio of four collinear points are represented: which are any one of the vertexes, and the two points that the ray initialing from the vertex intersects with the corresponding segments of the two curves, and the point the ray intersecting with the connecting line between the two neighboring vertexes. Different from rational quadratic Bézier curves, the value is generally related with the location of the ray, and the necessary and sufficient condition of the ratio being independent of the ray's location is showed. Also another cross ratio of the following four collinear points are suggested, i.e. one vertex, the points that the ray from the initial vertex intersects respectively with the curve segment, the line connecting the segments end points, and the line connecting the two neighboring vertexes. This cross ratio is concerned only with the ray's location, but not with the weights of the curve. Furthermore, the cross ratio is projective invariant under the projective transformation between the two segments.