The traditional deterministic analysis for tunnel face stability neglects the uncertainties of geotechnical parameters,while the simplified reliability analysis which models the potential uncertainties by means of ran...The traditional deterministic analysis for tunnel face stability neglects the uncertainties of geotechnical parameters,while the simplified reliability analysis which models the potential uncertainties by means of random variables usually fails to account for soil spatial variability.To overcome these limitations,this study proposes an efficient framework for conducting reliability analysis and reliability-based design(RBD)of tunnel face stability in spatially variable soil strata.The three-dimensional(3D)rotational failure mechanism of the tunnel face is extended to account for the soil spatial variability,and a probabilistic framework is established by coupling the extended mechanism with the improved Hasofer-Lind-Rackwits-Fiessler recursive algorithm(iHLRF)as well as its inverse analysis formulation.The proposed framework allows for rapid and precise reliability analysis and RBD of tunnel face stability.To demonstrate the feasibility and efficacy of the proposed framework,an illustrative case of tunnelling in frictional soils is presented,where the soil's cohesion and friction angle are modelled as two anisotropic cross-correlated lognormal random fields.The results show that the proposed method can accurately estimate the failure probability(or reliability index)regarding the tunnel face stability and can efficiently determine the required supporting pressure for a target reliability index with soil spatial variability being taken into account.Furthermore,this study reveals the impact of various factors on the support pressure,including coefficient of variation,cross-correlation between cohesion and friction angle,as well as autocorrelation distance of spatially variable soil strata.The results also demonstrate the feasibility of using the forward and/or inverse first-order reliability method(FORM)in high-dimensional stochastic problems.It is hoped that this study may provide a practical and reliable framework for determining the stability of tunnels in complex soil strata.展开更多
Hoek-Brown (HB) failure criterion is widely used to predict the strength of intact or heavily jointed rock mass. For stability analysis of rock slopes governed by the HB failure criterion, the equivalent linearity to ...Hoek-Brown (HB) failure criterion is widely used to predict the strength of intact or heavily jointed rock mass. For stability analysis of rock slopes governed by the HB failure criterion, the equivalent linearity to Mohr-Coulomb (MC) criterion is often adopted, leading to the well-known equivalent Mohr-Coulomb method (EMCM). Existing studies on EMCM analysis mainly consider the shear strength of rock material, while consideration of the tensile strength is rare. This contradicts the fact that the underlying tensile strength of rock mass has considerable impact on the rock slope stability in real world. In this regard, this paper proposes a limit analysis-based approach that can account for tension in the three-dimensional (3D) stability analysis of HB rock slope. This approach is established on the equivalent linearity of the HB criterion with consideration of tensile strength, known as the equivalent tension cut-off MC method (ETMCM), and using a horn-like 3D mechanism of limit analysis. The safety factor solutions given by the proposed approach are validated by previous studies and numerical results. Parametric studies are conducted to investigate the effect of rock tensile strength on slope stability. Results show that the consideration of tension leads to a more conservative safety factor and a sharper curvature of the failure surface, and these impacts tend to be more obvious with the increases in slope inclination and slope width. Finally, the stability of the HB rock slope under seepage conditions is studied using the proposed approach. The results indicate that the effect of tensile strength is highly remarkable in seepage circumstances.展开更多
In this study, a three-dimensional (3D) finite element modelling (FEM) analysis is carried out to investigate the effects of soil spatial variability on the response of retaining walls and an adjacent box culvert due ...In this study, a three-dimensional (3D) finite element modelling (FEM) analysis is carried out to investigate the effects of soil spatial variability on the response of retaining walls and an adjacent box culvert due to a braced excavation. The spatial variability of soil stiffness is modelled using a variogram and calibrated by high-quality experimental data. Multiple random field samples (RFSs) of soil stiffness are generated using geostatistical analysis and mapped onto a finite element mesh for stochastic analysis of excavation-induced structural responses by Monte Carlo simulation. It is found that the spatial variability of soil stiffness can be described by an exponential variogram, and the associated vertical correlation length is varied from 1.3 m to 1.6 m. It also reveals that the spatial variability of soil stiffness has a significant effect on the variations of retaining wall deflections and box culvert settlements. The ignorance of spatial variability in 3D FEM can result in an underestimation of lateral wall deflections and culvert settlements. Thus, the stochastic structural responses obtained from the 3D analysis could serve as an effective aid for probabilistic design and analysis of excavations.展开更多
针对输变电工程三维设计模型的多源、异构和模型整合应用所导致仿真系统设计难度大且数据管理和共享困难,而目前相关研究较少的问题,提出了一种面向输变电工程三维设计模型流程化整合方案。该方案基于SuperMap10平台和行业通用格式,采...针对输变电工程三维设计模型的多源、异构和模型整合应用所导致仿真系统设计难度大且数据管理和共享困难,而目前相关研究较少的问题,提出了一种面向输变电工程三维设计模型流程化整合方案。该方案基于SuperMap10平台和行业通用格式,采用模型层级分类、三维缓存技术、几何细节层次(levels of detail, LOD)优化体系和纹理优化等方法,设计出面向不同特性的三维设计模型与GIS数据融合方案。实验结果表明,该方案能在保证模型坐标系、属性和语义完整的同时,将不同三维模型格式的电力模型进行了统一,将有利于电力仿真系统的设计实现和进行电力数据协同分析;结合数据实际情况分析,对模型顶点和面进行针对性优化方法,使表面模型的数据量下降95%左右,并采用LOD模型构建和对场景进行三维缓存切片来控制场景性能,渲染时间较优化前减少约1倍;利用GIS软件二次开发接口,实现方案的流程化处理,大大减少了传统模式所需的人力资源。展开更多
To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply ...To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply formulated in x-space and requires neither transformation of correlated random variables nor optimization tools. The solution can be easily improved by iteratively adjusting the step length. The algorithm is particularly useful to practicing engineers for geotechnical reliability analysis where standalone(deterministic) numerical packages are used. Based on the proposed algorithm and through direct perturbation analysis of random variables, we conducted a case study of earth slope reliability with complete consideration of soil uncertainty and spatial variability.展开更多
Based on experimental results of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code(PFC2D). Then, the validation of the simulated models we...Based on experimental results of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code(PFC2D). Then, the validation of the simulated models were cross checked with the experimental results of brittle sandstone containing three parallel fissures under uniaxial compression. The simulated results agreed very well with the experimental results, including the peak strength, peak axial strain, and ultimate failure mode. Using the same microparameters, the numerical models containing a new geometry of three fissures are constructed to investigate the fissure angle on the fracture mechanical behavior of brittle sandstone under uniaxial compression. The strength and deformation parameters of brittle sandstone containing new three fissures are dependent to the fissure angle. With the increase of the fissure angle, the elastic modulus, the crack damage threshold,and the peak strength of brittle sandstone containing three fissures firstly increase and secondly decrease. But the peak axial strain is nonlinearly related to the fissure angle. In the entire process of deformation, the crack initiation and propagation behavior of brittle sandstone containing three fissures under uniaxial compression are investigated with respect tothe fissure angle. Six different crack coalescence modes are identified for brittle sandstone containing three fissures under uniaxial compression. The influence of the fissure angle on the length of crack propagation and crack coalescence stress is evaluated. These investigated conclusions are very important for ensuring the stability and safety of rock engineering with intermittent structures.展开更多
Heterogeneously catalyzed hydrolytic dehydrogenation of ammonia borane is a remarkable structure sensitive reaction. In this work, a strategy by using polyoxometalates(POMs) as the ligands is proposed to engineer the ...Heterogeneously catalyzed hydrolytic dehydrogenation of ammonia borane is a remarkable structure sensitive reaction. In this work, a strategy by using polyoxometalates(POMs) as the ligands is proposed to engineer the surface and electronic properties of Pt/CNT catalysts toward the enhanced hydrogen generation rate and durability. Three kinds of POMs, i.e., silicotungstic acid(STA), phosphotungstic acid(PTA)and molybdophosphoric acid(PMA), are comparatively studied, among which the STA shows positive effects on the catalytic activity and durability. A catalyst structure-performance relationship is established by a combination of kinetic and isotopic analyses with multiple characterization techniques, such as HAADF-STEM, EDS, Raman spectroscopy and XPS. It is shown that the STA compared to the other two POMs can increase the Pt binding energy and thus promote the reaction. The insights demonstrated here could open a new avenue for boosting the reaction by employing the POMs as the ligands to engineer the catalyst electronic properties.展开更多
This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenM...This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenMP parallel framework.Then,the applicability of this method was validated by comparing the generated random field with theoretical result and by simulating the post-failure process of an actual landslide.Thereafter,an illustrative landslide example was created and simulated to obtain the spatial variability effect of internal friction angle on the post-failure behavior of landslides under different coefficients of variation(COVs) and correlation lengths(CLs).As a conclusion,the reinforcement with materials of a larger friction angle can reduce the runout distance and impact the force of a landslide.As the increase of COV,the distribution range of influence zones also increases,which indicates that the deviation of influence zones becomes large.In addition,the correlation length in Monte Carlo simulations should not be too small,otherwise the variation range of influence zones will be underestimated.展开更多
Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivat...Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.展开更多
In order to maintain the safety of underground constructions that significantly involve geo-material uncertainties,this paper delivers a new computation framework for conducting reliability-based design(RBD)of shallow...In order to maintain the safety of underground constructions that significantly involve geo-material uncertainties,this paper delivers a new computation framework for conducting reliability-based design(RBD)of shallow tunnel face stability,utilizing a simplified inverse first-order reliability method(FORM).The limit state functions defining tunnel face stability are established for both collapse and blow-out modes of the tunnel face failure,respectively,and the deterministic results of the tunnel face support pressure are obtained through three-dimensional finite element limit analysis(FELA).Because the inverse reliability method can directly capture the design support pressure according to prescribed target reliability index,the computational cost for probabilistic design of tunnel face stability is greatly reduced.By comparison with Monte Carlo simulation results,the accuracy and feasibility of the proposed method are verified.Further,this study presents a series of reliability-based design charts for vividly understanding the limit support pressure on tunnel face in both cohesionless(sandy)soil and cohesive soil stratums,and their optimal support pressure ranges are highlighted.The results show that in the case of sandy soil stratum,the blowout failure of tunnel face is extremely unlikely,whereas the collapse is the only possible failure mode.The parametric study of various geotechnical uncertainties also reveals that ignoring the potential correlation between soil shear strength parameters will lead to over-designed support pressure,and the coefficient of variation of internal friction angle has a greater influence on the tunnel face failure probability than that of the cohesion.展开更多
Objective:To evaluate the bone metabolism balance and traumatic reaction of minimally invasive mippo intramedullary nail internal fixation treatment of femoral shaft fractures. Methods:80 patients with femoral shaft f...Objective:To evaluate the bone metabolism balance and traumatic reaction of minimally invasive mippo intramedullary nail internal fixation treatment of femoral shaft fractures. Methods:80 patients with femoral shaft fractures who were treated in our hospital between May 2011 and December 2016 were collected and divided into control group (n=40) and observation group (n=40) according to random number table, control group received conventional steel plate internal fixation treatment, and observation group received minimally invasive mippo intramedullary nail internal fixation treatment. Differences in serum levels of bone formation indexes, bone resorption indexes, inflammatory factors, and pain mediators and so on were compared between two groups of patients before operation and 1 week after treatment.Results: Before operation, differences in serum levels of bone formation indexes, bone resorption indexes, inflammatory factors and pain mediators were not statistically significant between two groups of patients. After operation, serum bone formation indexes P ICP, BGP, BALP and ALP levels in observation group were higher than those in control group;serum bone resorption indexesβ-CTX and OPG levels were lower than those in control group;serum inflammatory factors IL-1β, IL-6, IL-8 and CRP levels were lower than those in control group;serum pain mediators SP, PGE2 and 5-HT levels were lower than those in control group.Conclusion:Minimally invasive mippo intramedullary nail internal fixation treatment of femoral shaft fractures can promote the bone formation, relatively inhibit bone resorption and cause less traumatic reaction.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.U22A20594)the Fundamental Research Funds for the Central Universities(Grant No.B230205028)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX23_0694).
文摘The traditional deterministic analysis for tunnel face stability neglects the uncertainties of geotechnical parameters,while the simplified reliability analysis which models the potential uncertainties by means of random variables usually fails to account for soil spatial variability.To overcome these limitations,this study proposes an efficient framework for conducting reliability analysis and reliability-based design(RBD)of tunnel face stability in spatially variable soil strata.The three-dimensional(3D)rotational failure mechanism of the tunnel face is extended to account for the soil spatial variability,and a probabilistic framework is established by coupling the extended mechanism with the improved Hasofer-Lind-Rackwits-Fiessler recursive algorithm(iHLRF)as well as its inverse analysis formulation.The proposed framework allows for rapid and precise reliability analysis and RBD of tunnel face stability.To demonstrate the feasibility and efficacy of the proposed framework,an illustrative case of tunnelling in frictional soils is presented,where the soil's cohesion and friction angle are modelled as two anisotropic cross-correlated lognormal random fields.The results show that the proposed method can accurately estimate the failure probability(or reliability index)regarding the tunnel face stability and can efficiently determine the required supporting pressure for a target reliability index with soil spatial variability being taken into account.Furthermore,this study reveals the impact of various factors on the support pressure,including coefficient of variation,cross-correlation between cohesion and friction angle,as well as autocorrelation distance of spatially variable soil strata.The results also demonstrate the feasibility of using the forward and/or inverse first-order reliability method(FORM)in high-dimensional stochastic problems.It is hoped that this study may provide a practical and reliable framework for determining the stability of tunnels in complex soil strata.
基金supported by the National Natural Science Foundation of China(Grant Nos.U22A20594 and 52108312).
文摘Hoek-Brown (HB) failure criterion is widely used to predict the strength of intact or heavily jointed rock mass. For stability analysis of rock slopes governed by the HB failure criterion, the equivalent linearity to Mohr-Coulomb (MC) criterion is often adopted, leading to the well-known equivalent Mohr-Coulomb method (EMCM). Existing studies on EMCM analysis mainly consider the shear strength of rock material, while consideration of the tensile strength is rare. This contradicts the fact that the underlying tensile strength of rock mass has considerable impact on the rock slope stability in real world. In this regard, this paper proposes a limit analysis-based approach that can account for tension in the three-dimensional (3D) stability analysis of HB rock slope. This approach is established on the equivalent linearity of the HB criterion with consideration of tensile strength, known as the equivalent tension cut-off MC method (ETMCM), and using a horn-like 3D mechanism of limit analysis. The safety factor solutions given by the proposed approach are validated by previous studies and numerical results. Parametric studies are conducted to investigate the effect of rock tensile strength on slope stability. Results show that the consideration of tension leads to a more conservative safety factor and a sharper curvature of the failure surface, and these impacts tend to be more obvious with the increases in slope inclination and slope width. Finally, the stability of the HB rock slope under seepage conditions is studied using the proposed approach. The results indicate that the effect of tensile strength is highly remarkable in seepage circumstances.
基金The authors would like to acknowledge the financial support provided by the National Natural Science Foundation of China(Grant No.41977240)the Fundamental Research Funds for the Central Universities(Grant No.B200202090).
文摘In this study, a three-dimensional (3D) finite element modelling (FEM) analysis is carried out to investigate the effects of soil spatial variability on the response of retaining walls and an adjacent box culvert due to a braced excavation. The spatial variability of soil stiffness is modelled using a variogram and calibrated by high-quality experimental data. Multiple random field samples (RFSs) of soil stiffness are generated using geostatistical analysis and mapped onto a finite element mesh for stochastic analysis of excavation-induced structural responses by Monte Carlo simulation. It is found that the spatial variability of soil stiffness can be described by an exponential variogram, and the associated vertical correlation length is varied from 1.3 m to 1.6 m. It also reveals that the spatial variability of soil stiffness has a significant effect on the variations of retaining wall deflections and box culvert settlements. The ignorance of spatial variability in 3D FEM can result in an underestimation of lateral wall deflections and culvert settlements. Thus, the stochastic structural responses obtained from the 3D analysis could serve as an effective aid for probabilistic design and analysis of excavations.
文摘针对输变电工程三维设计模型的多源、异构和模型整合应用所导致仿真系统设计难度大且数据管理和共享困难,而目前相关研究较少的问题,提出了一种面向输变电工程三维设计模型流程化整合方案。该方案基于SuperMap10平台和行业通用格式,采用模型层级分类、三维缓存技术、几何细节层次(levels of detail, LOD)优化体系和纹理优化等方法,设计出面向不同特性的三维设计模型与GIS数据融合方案。实验结果表明,该方案能在保证模型坐标系、属性和语义完整的同时,将不同三维模型格式的电力模型进行了统一,将有利于电力仿真系统的设计实现和进行电力数据协同分析;结合数据实际情况分析,对模型顶点和面进行针对性优化方法,使表面模型的数据量下降95%左右,并采用LOD模型构建和对场景进行三维缓存切片来控制场景性能,渲染时间较优化前减少约1倍;利用GIS软件二次开发接口,实现方案的流程化处理,大大减少了传统模式所需的人力资源。
基金Financial supports from National Science Foundation of China(Grant Nos.51609072,51879091,51479050 and 41630638)the National Key Basic Research Program of China("973" Program)(Grant No.2015CB057901)the Public Service Sector R&D Project of Ministry of Water Resource of China(Grant No.201501035-03)
文摘To meet the high demand for reliability based design of slopes, we present in this paper a simplified HLRF(Hasofere Linde Rackwitze Fiessler) iterative algorithm for first-order reliability method(FORM). It is simply formulated in x-space and requires neither transformation of correlated random variables nor optimization tools. The solution can be easily improved by iteratively adjusting the step length. The algorithm is particularly useful to practicing engineers for geotechnical reliability analysis where standalone(deterministic) numerical packages are used. Based on the proposed algorithm and through direct perturbation analysis of random variables, we conducted a case study of earth slope reliability with complete consideration of soil uncertainty and spatial variability.
基金supported by the Fundamental Research Funds for the Central Universities (China University of Mining and Technology) (Grant 2014YC10)the National Basic Research 973 Program of China (Grant 2014CB046905)
文摘Based on experimental results of brittle, intact sandstone under uniaxial compression, the micro-parameters were firstly confirmed by adopting particle flow code(PFC2D). Then, the validation of the simulated models were cross checked with the experimental results of brittle sandstone containing three parallel fissures under uniaxial compression. The simulated results agreed very well with the experimental results, including the peak strength, peak axial strain, and ultimate failure mode. Using the same microparameters, the numerical models containing a new geometry of three fissures are constructed to investigate the fissure angle on the fracture mechanical behavior of brittle sandstone under uniaxial compression. The strength and deformation parameters of brittle sandstone containing new three fissures are dependent to the fissure angle. With the increase of the fissure angle, the elastic modulus, the crack damage threshold,and the peak strength of brittle sandstone containing three fissures firstly increase and secondly decrease. But the peak axial strain is nonlinearly related to the fissure angle. In the entire process of deformation, the crack initiation and propagation behavior of brittle sandstone containing three fissures under uniaxial compression are investigated with respect tothe fissure angle. Six different crack coalescence modes are identified for brittle sandstone containing three fissures under uniaxial compression. The influence of the fissure angle on the length of crack propagation and crack coalescence stress is evaluated. These investigated conclusions are very important for ensuring the stability and safety of rock engineering with intermittent structures.
基金supported by the National Natural Science Foundation of China(21776077)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning+3 种基金the Shanghai Rising-Star Program(17QA1401200)the Open Project of SKLOCE(SKL-Che-15C03)the Shanghai Natural Science Foundation(17ZR1407300 and 17ZR1407500)the State Key Laboratory of Organic-Inorganic Composites(oic201801007)。
文摘Heterogeneously catalyzed hydrolytic dehydrogenation of ammonia borane is a remarkable structure sensitive reaction. In this work, a strategy by using polyoxometalates(POMs) as the ligands is proposed to engineer the surface and electronic properties of Pt/CNT catalysts toward the enhanced hydrogen generation rate and durability. Three kinds of POMs, i.e., silicotungstic acid(STA), phosphotungstic acid(PTA)and molybdophosphoric acid(PMA), are comparatively studied, among which the STA shows positive effects on the catalytic activity and durability. A catalyst structure-performance relationship is established by a combination of kinetic and isotopic analyses with multiple characterization techniques, such as HAADF-STEM, EDS, Raman spectroscopy and XPS. It is shown that the STA compared to the other two POMs can increase the Pt binding energy and thus promote the reaction. The insights demonstrated here could open a new avenue for boosting the reaction by employing the POMs as the ligands to engineer the catalyst electronic properties.
基金This work is supported by the Natural Science Foundation of China(NSFC Grant No.51808192,51879091,41630638)the Natural Science Foundation of Jiangsu Province(Grant No.BK20170887)the China Postdoctoral Science Foundation(Grant Nos.2017M611673 and 2018T110432).We thank Ms.Ruihua Yu for her contribution in compiling some of the figures in this work.
文摘This study proposed a random Smoothed Particle Hydrodynamics method for analyzing the post-failure behavior of landslides,which is based on the Karhunen-Loeve(K-L) expansion,the non-Newtonian fluid model,and the OpenMP parallel framework.Then,the applicability of this method was validated by comparing the generated random field with theoretical result and by simulating the post-failure process of an actual landslide.Thereafter,an illustrative landslide example was created and simulated to obtain the spatial variability effect of internal friction angle on the post-failure behavior of landslides under different coefficients of variation(COVs) and correlation lengths(CLs).As a conclusion,the reinforcement with materials of a larger friction angle can reduce the runout distance and impact the force of a landslide.As the increase of COV,the distribution range of influence zones also increases,which indicates that the deviation of influence zones becomes large.In addition,the correlation length in Monte Carlo simulations should not be too small,otherwise the variation range of influence zones will be underestimated.
基金supported by the Natural Science Foundation of China (Grant Nos. 52022090, 22005265, 82070739, 81870641)National Key R&D Program of China (Grant No. 2018YFC1106104)+3 种基金Key Research and Development Program of Zhejiang Province (Grant No. 2020C03035)Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ20E030011)Zhejiang Medical Health Science and Technology Program (Grant No. 2021RC061)Zhejiang Provincial Ten Thousand Talents Program (2018R52001)。
文摘Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.
基金supported by the Natural Science Foundation of China[NSFC Grant Nos.51879091,52079045,41772287]support from the Key R&D Project of Zhejiang Province(2021C03159).
文摘In order to maintain the safety of underground constructions that significantly involve geo-material uncertainties,this paper delivers a new computation framework for conducting reliability-based design(RBD)of shallow tunnel face stability,utilizing a simplified inverse first-order reliability method(FORM).The limit state functions defining tunnel face stability are established for both collapse and blow-out modes of the tunnel face failure,respectively,and the deterministic results of the tunnel face support pressure are obtained through three-dimensional finite element limit analysis(FELA).Because the inverse reliability method can directly capture the design support pressure according to prescribed target reliability index,the computational cost for probabilistic design of tunnel face stability is greatly reduced.By comparison with Monte Carlo simulation results,the accuracy and feasibility of the proposed method are verified.Further,this study presents a series of reliability-based design charts for vividly understanding the limit support pressure on tunnel face in both cohesionless(sandy)soil and cohesive soil stratums,and their optimal support pressure ranges are highlighted.The results show that in the case of sandy soil stratum,the blowout failure of tunnel face is extremely unlikely,whereas the collapse is the only possible failure mode.The parametric study of various geotechnical uncertainties also reveals that ignoring the potential correlation between soil shear strength parameters will lead to over-designed support pressure,and the coefficient of variation of internal friction angle has a greater influence on the tunnel face failure probability than that of the cohesion.
文摘Objective:To evaluate the bone metabolism balance and traumatic reaction of minimally invasive mippo intramedullary nail internal fixation treatment of femoral shaft fractures. Methods:80 patients with femoral shaft fractures who were treated in our hospital between May 2011 and December 2016 were collected and divided into control group (n=40) and observation group (n=40) according to random number table, control group received conventional steel plate internal fixation treatment, and observation group received minimally invasive mippo intramedullary nail internal fixation treatment. Differences in serum levels of bone formation indexes, bone resorption indexes, inflammatory factors, and pain mediators and so on were compared between two groups of patients before operation and 1 week after treatment.Results: Before operation, differences in serum levels of bone formation indexes, bone resorption indexes, inflammatory factors and pain mediators were not statistically significant between two groups of patients. After operation, serum bone formation indexes P ICP, BGP, BALP and ALP levels in observation group were higher than those in control group;serum bone resorption indexesβ-CTX and OPG levels were lower than those in control group;serum inflammatory factors IL-1β, IL-6, IL-8 and CRP levels were lower than those in control group;serum pain mediators SP, PGE2 and 5-HT levels were lower than those in control group.Conclusion:Minimally invasive mippo intramedullary nail internal fixation treatment of femoral shaft fractures can promote the bone formation, relatively inhibit bone resorption and cause less traumatic reaction.
