Photonic spin Hall effect(PSHE), as a novel physical effect in light–matter interaction, provides an effective metrological method for characterizing the tiny variation in refractive index(RI). In this work, we propo...Photonic spin Hall effect(PSHE), as a novel physical effect in light–matter interaction, provides an effective metrological method for characterizing the tiny variation in refractive index(RI). In this work, we propose a multi-functional PSHE sensor based on VO_(2), a material that can reveal the phase transition behavior. By applying thermal control, the mutual transformation into different phase states of VO_(2) can be realized, which contributes to the flexible switching between multiple RI sensing tasks. When VO_(2) is insulating, the ultrasensitive detection of glucose concentrations in human blood is achieved. When VO_(2) is in a mixed phase, the structure can be designed to distinguish between the normal cells and cancer cells through no-label and real-time monitoring. When VO_(2) is metallic, the proposed PSHE sensor can act as an RI indicator for gas analytes. Compared with other multi-functional sensing devices with the complex structures, our design consists of only one analyte and two VO_(2) layers, which is very simple and elegant. Therefore, the proposed VO_(2)-based PSHE sensor has outstanding advantages such as small size, high sensitivity, no-label, and real-time detection, providing a new approach for investigating tunable multi-functional sensors.展开更多
To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforc...To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.展开更多
Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmo...Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.展开更多
目的分离纯化碧根果致敏原Car i 1,并对其结构进行表征鉴定。方法以新鲜碧根果果仁为原料,通过粉碎、脱脂、浸提、粗分级、凝胶过滤层析,对碧根果致敏原蛋白Car i 1进行分离纯化。结合十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、液相色谱-串...目的分离纯化碧根果致敏原Car i 1,并对其结构进行表征鉴定。方法以新鲜碧根果果仁为原料,通过粉碎、脱脂、浸提、粗分级、凝胶过滤层析,对碧根果致敏原蛋白Car i 1进行分离纯化。结合十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、液相色谱-串联质谱法和免疫印迹法3种方法对Cari1进行鉴定,并通过圆二色谱仪与紫外分光光度计表征其二、三级结构。结果本方法纯化获得碧根果致敏原Cari1,单轮制备量可达5 mg以上,且纯度大于95%,蛋白质高级结构未被破坏,能够被全部3名碧根果过敏患者的血清准确识别。结论该纯化方法技术路线简单、设备要求低且单次制备量高,总得率可达65%,操作便捷,为碧根果致敏原Car i 1的相关研究奠定了物质基础。展开更多
We propose a novel and efficient multi-functional optical fiber sensor system based on a dense wavelength division multiplexer(DWDM).This system consists of an optical fiber temperature sensor, an optical fiber strain...We propose a novel and efficient multi-functional optical fiber sensor system based on a dense wavelength division multiplexer(DWDM).This system consists of an optical fiber temperature sensor, an optical fiber strain sensor, and a 48-channel DWDM.This system can monitor temperature and strain changes at the same time.The ranges of these two sensors are from-20℃ to 100℃ and from-1000 με to 2000 με, respectively.The sensitivities of the temperature sensor and strain sensor are 0.03572 nm/℃ and 0.03808 nm/N, respectively.With the aid of a broadband source and spectrometer,different kinds and ranges of parameters in the environment can be monitored by using suitable sensors.展开更多
A compound multi-functional sensor was designed by the study on the on-line testing technology of wood-based panels, and its properties of shape, functions, size, resistance to special environment were studied in deta...A compound multi-functional sensor was designed by the study on the on-line testing technology of wood-based panels, and its properties of shape, functions, size, resistance to special environment were studied in details. The operational principles of different sensors, technical flow of manufacturing, development of software systems of special functions, and the assessments of technical specification were also be introduced. This sensor adopted many new technologies, such as the applications of piezoresistant effect and heat sensitive effect can effectively measure the pressure and temperature, digital signal processing technology was used to extract and treat signals, and resist interference, encapsulation technology was used to keep the normal run of sensor under a harsh environment. Thus, the on-line compound multi-functional temperature/pressure sensor can be applied better to supervise the production of wood-based panels. All technical specifications of the compound multi-functional sensor were tested and the results met the requirements of the equipments.展开更多
A new appraisal method（QDA, quasi-distribution appraisal） which could be used to evaluate the finite element analysis of multi-functional structure made of honeycomb sandwich materials is developed based on sub-sect...A new appraisal method（QDA, quasi-distribution appraisal） which could be used to evaluate the finite element analysis of multi-functional structure made of honeycomb sandwich materials is developed based on sub-section Bezier curve. It is established by simulating the distribution histogram data obtained from the numerical finite element analysis values of a satellite component with sub-section Bezier curve. Being dealt with area normalization method, the simulation curve could be regarded as a kind of probability density function（PDF）, its mathematical expectation and the variance could be used to evaluate the result of finite element analysis. Numerical experiments have indicated that the QDA method demonstrates the intrinsic characteristics of the finite element analysis of multi-functional structure made of honeycomb sandwich materials, as an appraisal method, it is effective and feasible.展开更多
Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion cha...Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.展开更多
In order to meet increasing demand for higher productivity and flexibility, recently many kinds of multi-functional machine tools, which are capable of multiple machining functions or different kinds of machining proc...In order to meet increasing demand for higher productivity and flexibility, recently many kinds of multi-functional machine tools, which are capable of multiple machining functions or different kinds of machining processes on one machine, have been developed and widely used in manufacturing industries. In this study, a multi-functional turning lathe, which has two spindles and two turrets so that multiple turning operations and various machining processes could be performed simultaneously, has been developed. Furthermore, the equations of correlation between whole responses and cross responses of the two spindles have been derived to examine to what extent the two spindles affect each other’s vibrations.展开更多
This study presents a design of a multifunctional laparoscopic appendectomy device that includes three surgical instruments commonly used in laparoscopic appendicitis surgeries:endoloop,endobag and scissors.It collect...This study presents a design of a multifunctional laparoscopic appendectomy device that includes three surgical instruments commonly used in laparoscopic appendicitis surgeries:endoloop,endobag and scissors.It collects these three independent surgical tools in a single laparoscopic appendectomy device.These days there is a trend of moving to multi-functional surgery devices during minimally invasive surgery.The main reasons behind the minimal invasive surgery are to avoid changing the devices several times during the operation,to reduce the time spent in operation,to increase the efficiency of the operation,to facilitate the follow-up of the camera and devices,and to leave trocars to be used for other surgical instruments.The multi-functional appendectomy device that,we present here,provides these benefits.The standard trocar entries are appropriate for its usage.The presented multifunctional laparoscopic appendectomy device offers more practical use in comparison to individual devices.On the other hand,development of these multi-functional surgery devices can be directly enhanced to the robotic surgery devices.展开更多
The experimental idea of the present project was elaborated in order to create a structure where different categories and institutions could collaborate, with the common aim to develop a sustainable and profitable agr...The experimental idea of the present project was elaborated in order to create a structure where different categories and institutions could collaborate, with the common aim to develop a sustainable and profitable agriculture in mountain and marginal areas. The target was the recovering of an abandoned agricultural site, throughout its re-organisation, re-qualification and auto-sustainability, involving local citizens. This approach was based on three further broad functions such as environmental, economic and social purposes. This cooperation, that allows the capitalization of local knowledge and the forging of relationships between local and external sources of expertise, information and advice, is fundamental to the future of existing rural communities, in particular in mountain areas. The model proposed, with the elaboration of a management software and technical agronomic sheets, could be an incentive for the activities already present in that region and to stimulate new ones. The enhancing of the native ecological system, the biodiversity tutelage and the valorization of the knowledge of the territory is the basic requirement for the successful of any land management.展开更多
The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administratio...The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.NSFC 12175107)the Natural Science Foundation of Nanjing Vocational University of Industry Technology,China(Grant No.YK22-02-08)+3 种基金the Qing Lan Project of Jiangsu Province,Chinathe Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.KYCX23_0964)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20230347)the Fund from the Research Center of Industrial Perception and Intelligent Manufacturing Equipment Engineering of Jiangsu Province,China(Grant No.ZK21-05-09)。
文摘Photonic spin Hall effect(PSHE), as a novel physical effect in light–matter interaction, provides an effective metrological method for characterizing the tiny variation in refractive index(RI). In this work, we propose a multi-functional PSHE sensor based on VO_(2), a material that can reveal the phase transition behavior. By applying thermal control, the mutual transformation into different phase states of VO_(2) can be realized, which contributes to the flexible switching between multiple RI sensing tasks. When VO_(2) is insulating, the ultrasensitive detection of glucose concentrations in human blood is achieved. When VO_(2) is in a mixed phase, the structure can be designed to distinguish between the normal cells and cancer cells through no-label and real-time monitoring. When VO_(2) is metallic, the proposed PSHE sensor can act as an RI indicator for gas analytes. Compared with other multi-functional sensing devices with the complex structures, our design consists of only one analyte and two VO_(2) layers, which is very simple and elegant. Therefore, the proposed VO_(2)-based PSHE sensor has outstanding advantages such as small size, high sensitivity, no-label, and real-time detection, providing a new approach for investigating tunable multi-functional sensors.
基金supported by the National Natural Science Foundations of China(Nos.5157051626,51475225)
文摘To fulfill the demands for higher quality,efficiency and flexibility in aviation industry,a multi-functional end effector is designed to automate the drilling and riveting processes in assembling carbon fiber reinforced polymer(CFRP)and aluminum components for a robotic aircraft assembly system.To meet the specific functional requirements for blind rivet installation on CFRP and aluminum materials,additional modules are incorporated on the end effector aside of the basic processing modules for drilling.And all of these processing modules allow for a onestep-drilling-countersinking process,hole inspection,automatic rivet feed,rivet geometry check,sealant application,rivet insertion and installation.Besides,to guarantee the better quality of the hole drilled and joints riveted,several online detection and adjustment measures are applied to this end effector,including the reference detection and perpendicular calibration,which could effectively ensure the positioning precision and perpendicular accuracy as demanded.Finally,the test result shows that this end effector is capable of producing each hole to a positioning precision within ±0.5 mm,aperpendicular accuracy within 0.3°,a diameter tolerance of H8,and a countersink depth tolerance of±0.01 mm.Moreover,it could drill and rivet up to three joints per minute,with acceptable shearing and tensile strength.
基金supported by grants from CAMS Innovation Fund for Medical Sciences(Grant No.:2021-I2M-1-026)Scientific Research Project of Tianjin Education Commission(Grant No.:2020KJ140)Tianjin Health Research Project(Grant No.:KJ20017)。
文摘Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.
文摘目的分离纯化碧根果致敏原Car i 1,并对其结构进行表征鉴定。方法以新鲜碧根果果仁为原料,通过粉碎、脱脂、浸提、粗分级、凝胶过滤层析,对碧根果致敏原蛋白Car i 1进行分离纯化。结合十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、液相色谱-串联质谱法和免疫印迹法3种方法对Cari1进行鉴定,并通过圆二色谱仪与紫外分光光度计表征其二、三级结构。结果本方法纯化获得碧根果致敏原Cari1,单轮制备量可达5 mg以上,且纯度大于95%,蛋白质高级结构未被破坏,能够被全部3名碧根果过敏患者的血清准确识别。结论该纯化方法技术路线简单、设备要求低且单次制备量高,总得率可达65%,操作便捷,为碧根果致敏原Car i 1的相关研究奠定了物质基础。
基金Project supported by the National Key Research and Development Program of China(Grant No.2016YFB0402504)the National Natural Science Foundation of China(Grant Nos.61875069 and 61575076)+1 种基金Hong Kong Scholars Program,China(Grant No.XJ2016026)the Science and Technology Development Plan of Jilin Province,China(Grant Nos.20190302010GX and 20160520091JH)
文摘We propose a novel and efficient multi-functional optical fiber sensor system based on a dense wavelength division multiplexer(DWDM).This system consists of an optical fiber temperature sensor, an optical fiber strain sensor, and a 48-channel DWDM.This system can monitor temperature and strain changes at the same time.The ranges of these two sensors are from-20℃ to 100℃ and from-1000 με to 2000 με, respectively.The sensitivities of the temperature sensor and strain sensor are 0.03572 nm/℃ and 0.03808 nm/N, respectively.With the aid of a broadband source and spectrometer,different kinds and ranges of parameters in the environment can be monitored by using suitable sensors.
基金This project was supported by China Postdoctoral Science Funds, Jiangsu Planned Projects for Postdoctoral Research Funds and Northeast Forestry University Research Funds.
文摘A compound multi-functional sensor was designed by the study on the on-line testing technology of wood-based panels, and its properties of shape, functions, size, resistance to special environment were studied in details. The operational principles of different sensors, technical flow of manufacturing, development of software systems of special functions, and the assessments of technical specification were also be introduced. This sensor adopted many new technologies, such as the applications of piezoresistant effect and heat sensitive effect can effectively measure the pressure and temperature, digital signal processing technology was used to extract and treat signals, and resist interference, encapsulation technology was used to keep the normal run of sensor under a harsh environment. Thus, the on-line compound multi-functional temperature/pressure sensor can be applied better to supervise the production of wood-based panels. All technical specifications of the compound multi-functional sensor were tested and the results met the requirements of the equipments.
基金Funded by the National Natural Science Foundation of China(No.61471024)National Marine Technology Program for Public Welfare,China(No.201505002-1)
文摘A new appraisal method（QDA, quasi-distribution appraisal） which could be used to evaluate the finite element analysis of multi-functional structure made of honeycomb sandwich materials is developed based on sub-section Bezier curve. It is established by simulating the distribution histogram data obtained from the numerical finite element analysis values of a satellite component with sub-section Bezier curve. Being dealt with area normalization method, the simulation curve could be regarded as a kind of probability density function（PDF）, its mathematical expectation and the variance could be used to evaluate the result of finite element analysis. Numerical experiments have indicated that the QDA method demonstrates the intrinsic characteristics of the finite element analysis of multi-functional structure made of honeycomb sandwich materials, as an appraisal method, it is effective and feasible.
文摘Calcium is a critical second messenger molecule in all cells and is vital in neurons for synaptic transmission.Given this importance,calcium ions are tightly controlled by a host of molecular players including ion channels,sensors,and buffering proteins.Calcium can act directly by binding to signaling molecules or calcium’s effects can be indirect,for example by altering nuclear histones.
文摘In order to meet increasing demand for higher productivity and flexibility, recently many kinds of multi-functional machine tools, which are capable of multiple machining functions or different kinds of machining processes on one machine, have been developed and widely used in manufacturing industries. In this study, a multi-functional turning lathe, which has two spindles and two turrets so that multiple turning operations and various machining processes could be performed simultaneously, has been developed. Furthermore, the equations of correlation between whole responses and cross responses of the two spindles have been derived to examine to what extent the two spindles affect each other’s vibrations.
文摘This study presents a design of a multifunctional laparoscopic appendectomy device that includes three surgical instruments commonly used in laparoscopic appendicitis surgeries:endoloop,endobag and scissors.It collects these three independent surgical tools in a single laparoscopic appendectomy device.These days there is a trend of moving to multi-functional surgery devices during minimally invasive surgery.The main reasons behind the minimal invasive surgery are to avoid changing the devices several times during the operation,to reduce the time spent in operation,to increase the efficiency of the operation,to facilitate the follow-up of the camera and devices,and to leave trocars to be used for other surgical instruments.The multi-functional appendectomy device that,we present here,provides these benefits.The standard trocar entries are appropriate for its usage.The presented multifunctional laparoscopic appendectomy device offers more practical use in comparison to individual devices.On the other hand,development of these multi-functional surgery devices can be directly enhanced to the robotic surgery devices.
文摘The experimental idea of the present project was elaborated in order to create a structure where different categories and institutions could collaborate, with the common aim to develop a sustainable and profitable agriculture in mountain and marginal areas. The target was the recovering of an abandoned agricultural site, throughout its re-organisation, re-qualification and auto-sustainability, involving local citizens. This approach was based on three further broad functions such as environmental, economic and social purposes. This cooperation, that allows the capitalization of local knowledge and the forging of relationships between local and external sources of expertise, information and advice, is fundamental to the future of existing rural communities, in particular in mountain areas. The model proposed, with the elaboration of a management software and technical agronomic sheets, could be an incentive for the activities already present in that region and to stimulate new ones. The enhancing of the native ecological system, the biodiversity tutelage and the valorization of the knowledge of the territory is the basic requirement for the successful of any land management.
基金supported by the National Natural Science Foundation of China(Grant Nos.82073934,81872937,and 81673513).
文摘The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.
