Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predic...Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.展开更多
It aims to investigate the protective effects of sodium hyaluronate,panthenol,Portulaca oleracea L.and Calendula officinalis L.on hyperosmotic dehydration-induced injury of human immortalized keratinocytes(HaCaT).The ...It aims to investigate the protective effects of sodium hyaluronate,panthenol,Portulaca oleracea L.and Calendula officinalis L.on hyperosmotic dehydration-induced injury of human immortalized keratinocytes(HaCaT).The safety mass concentrations of four raw materials were screened by detecting cell viability,and the secretion of hyaluronic acid(HA)was determined using the ELISA method.The expression of HaCaT barrier function related genes(OVOL1,EREG,TGM1,TGM2,IVL,IRF6,THBS1,CASP14)was detected at the mRNA level to explore the regulatory effect of four raw materials on these genes.The results demonstrate that pretreatment with the four kinds of raw materials could increase the cell viability after hyperosmotic dehydration,promote the secretion of HA,and improve the expression of barrier function related genes after hyperosmotic dehydration,among which panthenol and Calendula officinalis L.are better.The results show that the four raw materials have a certain protective effect on the hyperosmotic dehydration cell model,which provides data support for its application in cosmetics.展开更多
When the proton exchange membrane fuel cell(PEMFC)system is running,there will be a condition that does not require power output for a short time.In order to achieve zero power output under low power consumption,it is...When the proton exchange membrane fuel cell(PEMFC)system is running,there will be a condition that does not require power output for a short time.In order to achieve zero power output under low power consumption,it is necessary to consider the diversity of control targets and the complexity of dynamic models,which brings the challenge of high-precision tracking control of the stack output power and cathode intake flow.For system idle speed control,a modelbased nonlinear control framework is constructed in this paper.Firstly,the nonlinear dynamic model of output power and cathode intake flow is derived.Secondly,a control scheme combining nonlinear extended Kalman filter observer and state feedback controller is designed.Finally,the control scheme is verified on the PEMFC experimental platform and compared with the proportion-integration-differentiation(PID)controller.The experimental results show that the control strategy proposed in this paper can realize the idle speed control of the fuel cell system and achieve the purpose of zero power output.Compared with PID controller,it has faster response speed and better system dynamics.展开更多
The objective of this work is to develop a novel feature for traffic flow models, when traffic queues on two-way arterials periodically extend until then they block an upstream signal in oversaturated conditions. The ...The objective of this work is to develop a novel feature for traffic flow models, when traffic queues on two-way arterials periodically extend until then they block an upstream signal in oversaturated conditions. The new model, proposed as conditional cell transmission model （CCTM） has been developed with two improvements. First, cell transmission model （CTM） is expanded for two-way arterials by taking account of all diverging and merging activities at intersections. Second, a conditional cell is added to simulate periodic spillback and blockages at an intersection. The results of experiments for a multilane, two-way, three-signal sample network demonstrate that CCTM can accommodate various traffic demands and accurate representation of blockages at intersections. The delay of left turns is underestimated by 40 % in moderate conditions and by 58% in oversamrated condition when using the CTM rather than CCTM. Finally, the consistency between HCS 2000 and CCTM shows that CCTM is a reliable methodology of modeling traffic flow in oversaturated condition.展开更多
A water balance has a significant impact on the overall system performance in proton exchange membrane fuel cell.An actual fuel cell application has a dynamic electrical load which means also dynamic electrical curren...A water balance has a significant impact on the overall system performance in proton exchange membrane fuel cell.An actual fuel cell application has a dynamic electrical load which means also dynamic electrical current.Therefore,since this electrical current is known,the water production from the fuel cell reaction is also able to be predicted.As long as the fuel cell water transportation model is provided,the present liquid water inside the porous medium is also able to be modeled.A model of the liquid water saturation level in a fuel cell in unsteady load condition was proposed.This model is a series of the water transportation model of water saturation level for the final output of proton exchange membrane(PEM) fuel cell to predict the flooding or drying of PEM fuel cell.The simulation of vehicle fuel cell in different dynamic load profiles and different inlet air conditions was done using this model.The simulation result shows that PEM fuel cell with different dynamic load profiles has different liquid water saturation level profiles.This means that a dynamic load fuel cell requires also a dynamic input air humidification.展开更多
A novel conditional cell transmission model （CCTM） is a potential simulation tool because it accommodates all traffic conditions from light condition to oversaturated condition. To test the performance of the CCTM, ...A novel conditional cell transmission model （CCTM） is a potential simulation tool because it accommodates all traffic conditions from light condition to oversaturated condition. To test the performance of the CCTM, a series of experiments for sensitivity analysis were designed and performed for a multilane, two-way, three-signal sample network. Experiment 1 shows that the model is performed in a logical and expected manner with variations in traffic demand with time and direction. Experiment 2 shows when the possibility of the occurrence of a useful gap increases to 60% and 100%, the delays in left rams decrease by 5% and 15%, respectively. In Experiment 3, comparing the possibility of a conditional cell of 0 with 100%, delay of left turn and delay of the entire network were underestimated by 58% and 11%, respectively. Hence, sensitivity analysis demonstrates that by reflecting local drivers＇ behaviors properly, the CCTM provides an accurate representation of traffic flow in simulating oversaturated traffic conditions.展开更多
In order to investigate enhancements to cell transmission model (CTM) as a tool for traffic signal timing in oversaturated conditions, randomly distributed saturation flow rates and arrival rates were used instead of ...In order to investigate enhancements to cell transmission model (CTM) as a tool for traffic signal timing in oversaturated conditions, randomly distributed saturation flow rates and arrival rates were used instead of constant values to simulate traffic flow movement, estimate the average delay of the network and search for an optimal traffic signal timing plan. A case study was given to demonstrate that the proposed methodology can capture unique phenomena in oversaturated conditions such as forward wave, spillback and lane entrance blockage. The results show that CTM underestimates travel time by 25% when compared to Simtraffic, while the enhanced CTM underestimates by only 3%. A second case study shows that a dynamic signal timing plan is superior to a fixed signal timing plan in the term of average delay.展开更多
Background The mechanical properties are related with many biological functions of cells. Accurate quantification of the mechanical properties of living cells require the combined use of experimental techniques and th...Background The mechanical properties are related with many biological functions of cells. Accurate quantification of the mechanical properties of living cells require the combined use of experimental techniques and theoretical models. Micropipette aspiration (MPA) is one of common techniques in determining mechanical properties of the living cells. The halfspace model (HSM) is employed in MPA technique. However,in the conditions of linear constitutive relations and small deformations,the HSM is inadequate for characterizing the MPA of a spherical cell in two respects. Firstly,the cell size is fairly finite other than semi-infinite to the inner radius of a micropipette;Secondly,cells are compressible,with a Poisson’s ratioνvarying from 0. 2 to 0. 4 (23-25) instead of incompressible (ν=0. 5). Thus,a more accurate model is necessary.In this study,the viscoelastic expressions were derived from our previous MPA test. Then,a sphere model (SM) employed to analyze mechanical properties of rabbit chondrocytes combined with the experimental data. Differences in mechanical properties estimated by different mechanical models were evaluated.Methods A sphere model (SM) was employed. The relative dimension of cell to micropipette and the compressibility of the cell were taken into account,as shown in Fig. 1a.■Fig.1 Sphere model of the MPA of a single cell employing different constitutive relationships The approximate expression for the aspirated length was obtained from our previous study as follows:■Furthermore,assuming that the cell behaves as a homogeneous and isotropic standard linear solid (Fig. 1b),two viscoelastic creep expressions of the aspirated length for incompressible sphere model (ICSM) and for compressible sphere model (CSM) were derived by elastic-viscoelastic correspondence principle and integral transformation as Eqs.(2) and (3)respectively.■Results(1) Comparisons of models The elastic modulus from the ICSM was 47. 4%higher than that of the half-space model (HSM)(P<0. 001). For the CSM,the percentage increase in E over the value for the HSM was 87. 7%,78. 9%,and 64. 9%when the Poisson’s ratio was set to 0. 2,0. 3,and 0. 4,respectively.For the viscoelasticity,the parameters for the ICSM and CSM were significantly larger than those of the HSM (P <0. 001). The k1,k2,andμfor the ICSM were 37. 8%,37. 9%,and 39. 0%higher,respectively,than those of the HSM. For the CSM,the viscoelastic parameters decreased with the increase ofν. Whenν=0. 3,k1,k2,andμincreased by 71. 0%,200%,and 157%,respectively,compared to those of the ICSM (P<0. 001);For the cases ofν=0. 2 andν=0. 4,the above parameters were respectively 102%,243%,and 209%and 35. 3%,97. 5%,and 79%higher than those of the ICSM.(2) Predictions for the relative errors of mechanical parameters caused by HSM e is defined as the relative change of elastic moduli (or relative error) between the HSM and SM. As shown in Fig. 2,when Poisson’s ratioνis 0. 3,in order to let the e less than 30%,relative dimension between the cell and the micropipetteξneeds to be at least 5. 0. Whenνequals 0. 5 (ICSM),ξis about 3. 3 to make the e reach 20%. However,ξis rarely larger than 5. 0 in general MPA experiments,thus the relative error of modulus will exceed 30%. The above results are independent of cell types,thus they are applicable to other spherical solid-like cells.■Fig.2 Thresholds ofξvarying withνwhen e was 10%,20%,and 30%,respectively Another parameter VR was introduced to represent the relative errors of viscoelastic parameters between HSM and SM.With regard to ICSM (Fig. 3a),whenξis 3,VRis nearly 22%. If theξis larger than 8. 0,the relative error will be reduced to less than 10%. For the CSM,the viscoelastic parameters of a typical chondrocyte varying withξandνwere obtained,as shown from Figs. 3b to 3d. Whenνtends to 0. 5,the parameters tend to those of ICSM. When theξexceeds 10,each parameter changes very little. For a certain Poisson’s ratio (ν=0. 3),whenξis 3,the VR of k1,k2,andμare 47. 1%,70. 8%,and 68. 2%,respectively. Whenξequals 5 and 10,the above values are 42. 3%,68. 8%,65%,and 38. 4%,66. 0%,63. 2%,respectively. For a givenξ(ξ=3),whenνis 0. 2,the VR of k1,k2,andμare 53. 6%,73. 3%,and 75. 0%,respectively.Whenνis taken as 0. 3 and 0. 4,the above errors are 47. 7%,71. 1%,68. 2%,and 38. 4%,58. 8%,54. 8%,respectively.Thus,the VR also decreases with the increase ofξandν.Conclusions The effects of the relative dimension between the cell,and micropipette and the Poisson’s ratio of cell were remarkable and should be taken into consideration in the pursuit of more accurate mechanical parameters of cells.展开更多
基金国家自然科学基金项目(No.81902513)山西省应用基础研究计划项目(No.202303021211114 and 202103021224228)山西省高等教育百亿工程“科技引导”专项(No.BYJL047)资助。
文摘Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8^(+)T cell immune infiltration and immune suppression.We constructed a CD8^(+)T cells related risk score model to predict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8^(+)T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS 2,and TNFRSF1B was constructed.The risk score model was well validated through an independent external validation cohort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8^(+)T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity analysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene model was verified by immunohistochemistry.In summary,the establishment and validation of a CD8^(+)T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
文摘It aims to investigate the protective effects of sodium hyaluronate,panthenol,Portulaca oleracea L.and Calendula officinalis L.on hyperosmotic dehydration-induced injury of human immortalized keratinocytes(HaCaT).The safety mass concentrations of four raw materials were screened by detecting cell viability,and the secretion of hyaluronic acid(HA)was determined using the ELISA method.The expression of HaCaT barrier function related genes(OVOL1,EREG,TGM1,TGM2,IVL,IRF6,THBS1,CASP14)was detected at the mRNA level to explore the regulatory effect of four raw materials on these genes.The results demonstrate that pretreatment with the four kinds of raw materials could increase the cell viability after hyperosmotic dehydration,promote the secretion of HA,and improve the expression of barrier function related genes after hyperosmotic dehydration,among which panthenol and Calendula officinalis L.are better.The results show that the four raw materials have a certain protective effect on the hyperosmotic dehydration cell model,which provides data support for its application in cosmetics.
基金Supported by the Major Science and Technology Projects in Jilin Province and Changchun City(20220301010GX).
文摘When the proton exchange membrane fuel cell(PEMFC)system is running,there will be a condition that does not require power output for a short time.In order to achieve zero power output under low power consumption,it is necessary to consider the diversity of control targets and the complexity of dynamic models,which brings the challenge of high-precision tracking control of the stack output power and cathode intake flow.For system idle speed control,a modelbased nonlinear control framework is constructed in this paper.Firstly,the nonlinear dynamic model of output power and cathode intake flow is derived.Secondly,a control scheme combining nonlinear extended Kalman filter observer and state feedback controller is designed.Finally,the control scheme is verified on the PEMFC experimental platform and compared with the proportion-integration-differentiation(PID)controller.The experimental results show that the control strategy proposed in this paper can realize the idle speed control of the fuel cell system and achieve the purpose of zero power output.Compared with PID controller,it has faster response speed and better system dynamics.
基金Project(51108343) supported by the National Natural Science Foundation of ChinaProject(06121) supported by University of Transportation Center for Alabama,USA
文摘The objective of this work is to develop a novel feature for traffic flow models, when traffic queues on two-way arterials periodically extend until then they block an upstream signal in oversaturated conditions. The new model, proposed as conditional cell transmission model （CCTM） has been developed with two improvements. First, cell transmission model （CTM） is expanded for two-way arterials by taking account of all diverging and merging activities at intersections. Second, a conditional cell is added to simulate periodic spillback and blockages at an intersection. The results of experiments for a multilane, two-way, three-signal sample network demonstrate that CCTM can accommodate various traffic demands and accurate representation of blockages at intersections. The delay of left turns is underestimated by 40 % in moderate conditions and by 58% in oversamrated condition when using the CTM rather than CCTM. Finally, the consistency between HCS 2000 and CCTM shows that CCTM is a reliable methodology of modeling traffic flow in oversaturated condition.
文摘A water balance has a significant impact on the overall system performance in proton exchange membrane fuel cell.An actual fuel cell application has a dynamic electrical load which means also dynamic electrical current.Therefore,since this electrical current is known,the water production from the fuel cell reaction is also able to be predicted.As long as the fuel cell water transportation model is provided,the present liquid water inside the porous medium is also able to be modeled.A model of the liquid water saturation level in a fuel cell in unsteady load condition was proposed.This model is a series of the water transportation model of water saturation level for the final output of proton exchange membrane(PEM) fuel cell to predict the flooding or drying of PEM fuel cell.The simulation of vehicle fuel cell in different dynamic load profiles and different inlet air conditions was done using this model.The simulation result shows that PEM fuel cell with different dynamic load profiles has different liquid water saturation level profiles.This means that a dynamic load fuel cell requires also a dynamic input air humidification.
基金Project(51108343)supported by the National Natural Science Foundation of ChinaProject(06121)supported by University of Transportation Center for Alabama,USA
文摘A novel conditional cell transmission model （CCTM） is a potential simulation tool because it accommodates all traffic conditions from light condition to oversaturated condition. To test the performance of the CCTM, a series of experiments for sensitivity analysis were designed and performed for a multilane, two-way, three-signal sample network. Experiment 1 shows that the model is performed in a logical and expected manner with variations in traffic demand with time and direction. Experiment 2 shows when the possibility of the occurrence of a useful gap increases to 60% and 100%, the delays in left rams decrease by 5% and 15%, respectively. In Experiment 3, comparing the possibility of a conditional cell of 0 with 100%, delay of left turn and delay of the entire network were underestimated by 58% and 11%, respectively. Hence, sensitivity analysis demonstrates that by reflecting local drivers＇ behaviors properly, the CCTM provides an accurate representation of traffic flow in simulating oversaturated traffic conditions.
基金Project(51108343) supported by the National Natural Science Foundation of ChinaProject(06121) supported by University of Transportation Center for Alabama, USA
文摘In order to investigate enhancements to cell transmission model (CTM) as a tool for traffic signal timing in oversaturated conditions, randomly distributed saturation flow rates and arrival rates were used instead of constant values to simulate traffic flow movement, estimate the average delay of the network and search for an optimal traffic signal timing plan. A case study was given to demonstrate that the proposed methodology can capture unique phenomena in oversaturated conditions such as forward wave, spillback and lane entrance blockage. The results show that CTM underestimates travel time by 25% when compared to Simtraffic, while the enhanced CTM underestimates by only 3%. A second case study shows that a dynamic signal timing plan is superior to a fixed signal timing plan in the term of average delay.
文摘Background The mechanical properties are related with many biological functions of cells. Accurate quantification of the mechanical properties of living cells require the combined use of experimental techniques and theoretical models. Micropipette aspiration (MPA) is one of common techniques in determining mechanical properties of the living cells. The halfspace model (HSM) is employed in MPA technique. However,in the conditions of linear constitutive relations and small deformations,the HSM is inadequate for characterizing the MPA of a spherical cell in two respects. Firstly,the cell size is fairly finite other than semi-infinite to the inner radius of a micropipette;Secondly,cells are compressible,with a Poisson’s ratioνvarying from 0. 2 to 0. 4 (23-25) instead of incompressible (ν=0. 5). Thus,a more accurate model is necessary.In this study,the viscoelastic expressions were derived from our previous MPA test. Then,a sphere model (SM) employed to analyze mechanical properties of rabbit chondrocytes combined with the experimental data. Differences in mechanical properties estimated by different mechanical models were evaluated.Methods A sphere model (SM) was employed. The relative dimension of cell to micropipette and the compressibility of the cell were taken into account,as shown in Fig. 1a.■Fig.1 Sphere model of the MPA of a single cell employing different constitutive relationships The approximate expression for the aspirated length was obtained from our previous study as follows:■Furthermore,assuming that the cell behaves as a homogeneous and isotropic standard linear solid (Fig. 1b),two viscoelastic creep expressions of the aspirated length for incompressible sphere model (ICSM) and for compressible sphere model (CSM) were derived by elastic-viscoelastic correspondence principle and integral transformation as Eqs.(2) and (3)respectively.■Results(1) Comparisons of models The elastic modulus from the ICSM was 47. 4%higher than that of the half-space model (HSM)(P<0. 001). For the CSM,the percentage increase in E over the value for the HSM was 87. 7%,78. 9%,and 64. 9%when the Poisson’s ratio was set to 0. 2,0. 3,and 0. 4,respectively.For the viscoelasticity,the parameters for the ICSM and CSM were significantly larger than those of the HSM (P <0. 001). The k1,k2,andμfor the ICSM were 37. 8%,37. 9%,and 39. 0%higher,respectively,than those of the HSM. For the CSM,the viscoelastic parameters decreased with the increase ofν. Whenν=0. 3,k1,k2,andμincreased by 71. 0%,200%,and 157%,respectively,compared to those of the ICSM (P<0. 001);For the cases ofν=0. 2 andν=0. 4,the above parameters were respectively 102%,243%,and 209%and 35. 3%,97. 5%,and 79%higher than those of the ICSM.(2) Predictions for the relative errors of mechanical parameters caused by HSM e is defined as the relative change of elastic moduli (or relative error) between the HSM and SM. As shown in Fig. 2,when Poisson’s ratioνis 0. 3,in order to let the e less than 30%,relative dimension between the cell and the micropipetteξneeds to be at least 5. 0. Whenνequals 0. 5 (ICSM),ξis about 3. 3 to make the e reach 20%. However,ξis rarely larger than 5. 0 in general MPA experiments,thus the relative error of modulus will exceed 30%. The above results are independent of cell types,thus they are applicable to other spherical solid-like cells.■Fig.2 Thresholds ofξvarying withνwhen e was 10%,20%,and 30%,respectively Another parameter VR was introduced to represent the relative errors of viscoelastic parameters between HSM and SM.With regard to ICSM (Fig. 3a),whenξis 3,VRis nearly 22%. If theξis larger than 8. 0,the relative error will be reduced to less than 10%. For the CSM,the viscoelastic parameters of a typical chondrocyte varying withξandνwere obtained,as shown from Figs. 3b to 3d. Whenνtends to 0. 5,the parameters tend to those of ICSM. When theξexceeds 10,each parameter changes very little. For a certain Poisson’s ratio (ν=0. 3),whenξis 3,the VR of k1,k2,andμare 47. 1%,70. 8%,and 68. 2%,respectively. Whenξequals 5 and 10,the above values are 42. 3%,68. 8%,65%,and 38. 4%,66. 0%,63. 2%,respectively. For a givenξ(ξ=3),whenνis 0. 2,the VR of k1,k2,andμare 53. 6%,73. 3%,and 75. 0%,respectively.Whenνis taken as 0. 3 and 0. 4,the above errors are 47. 7%,71. 1%,68. 2%,and 38. 4%,58. 8%,54. 8%,respectively.Thus,the VR also decreases with the increase ofξandν.Conclusions The effects of the relative dimension between the cell,and micropipette and the Poisson’s ratio of cell were remarkable and should be taken into consideration in the pursuit of more accurate mechanical parameters of cells.
