A partly clumped-particles combined with joint planes model was developed to simulate the microstructure of quartz mica schist.It considers grain-scale heterogeneity including microgeometry heterogeneity and grain-sca...A partly clumped-particles combined with joint planes model was developed to simulate the microstructure of quartz mica schist.It considers grain-scale heterogeneity including microgeometry heterogeneity and grain-scale elastic heterogeneity.Clumped-particles with larger volume and larger stiffness were used to represent stiff minerals such as quartz,the rest of unclumped particles with smaller stiffness were used to represent soft minerals such as mica.The joint planes,which have smaller stiffness and strength than mica,were used to describe schist.The extensive sensitivity studies have shown that the clump’s radius,clump’s content and joint plane’s strength affect the microscopic and macroscopic behaviors of sample.For DanBa quartz mica schist,the model calibrated uniaxial tests and well matched with the stress-strain curves,crack initiation stress and crack damage stress of laboratory test.展开更多
BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart fro...BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient(MMR-P)or microsatellite stable(MSS)counterparts.CRCs have several prognostic factors,including stage,tumor differentiation,location,lymphovascular and perineural invasion,tumor budding,tumor infiltrating lymphocytes,lymph node yield(LNY),and lymph node ratio(LNR).AIM To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.METHODS This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment.Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides.MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.RESULTS Of the 223 patients in our study,87(39.01%)were MMR-D/MSI-H CRCs while 136(60.99%)were MMR-P/MSS CRCs.The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors,including location,stage,tumor budding,lymphovascular and perineural invasion,lymphocytic response,LNY,LNR,and size of uninvolved lymph nodes.LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group(P=0.003 and P<0.001,respectively).Also,the interquartile range of the largest uninvolved lymph node was 1 cm(0.8 cm-1.2 cm)in MMR-D/MSI-H CRCs compared to 0.7 cm(0.6 cm-0.97 cm)in MMRP/MSS CRCs.The overall survival for the MMR-P/MSS CRC group was 71%at five years,and the MMR-D/MSIH CRC group was 92%at five years(P<0.001).CONCLUSION MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics,including an enhanced immune response.This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.展开更多
Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECK...Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.展开更多
BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the...BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.展开更多
Welding of high strength low alloy steels (HSLA) involves usage of low, even and high strength filler materials (electrodes) than the parent material depending on the application of the welded structures and the avail...Welding of high strength low alloy steels (HSLA) involves usage of low, even and high strength filler materials (electrodes) than the parent material depending on the application of the welded structures and the availability of the filler material. In the present investigation, the fatigue crack growth behaviour of weld metal (WM) and heat affected zone (HAZ) regions of under matched (UM), equal matched (EM) and over matched (OM) joints has been studied. The base material used in this investigation is HSLA-80 steel of weldable grade. Shielded metal arc welding (SMAW) process has been used to fabricate the butt joints. Centre cracked tension (CCT) specimen has been used to evaluate the fatigue crack growth behaviour of the welded joints. Fatigue crack growth experiments have been conducted using servo hydraulic controlled fatigue testing machine at constant amplitude loading (R=0).A method has been proposed to predict the fatigue life of HSLA steel welds using fracture mechanics approach by incorporating influences of mismatch ratio (MMR) and notch location.展开更多
In this paper, an adaptive full order sliding mode （FOSM） controller is proposed for strict feedback nonlinear systems with mismatched uncertainties. The design objective of the controller is to track a specified tr...In this paper, an adaptive full order sliding mode （FOSM） controller is proposed for strict feedback nonlinear systems with mismatched uncertainties. The design objective of the controller is to track a specified trajectory in presence of significant mismatched uncertainties. In the first step the dynamic model for the first state is considered by the desired tracking signal. After the first step the desired dynamic model for each state is defined by the previous one. An adaptive tuning law is developed for the FOSM controller to deal with the bounded system uncertainty. The major advantages offered by this adaptive FOSM controller are that advanced knowledge about the upper bound of the system uncertainties is not a necessary requirement and the proposed method is an effective solution for the chattering elimination from the control signal. The controller is designed considering the full-order sliding surface. System robustness and the stability of the controller are proved by using the Lyapunov technique. A systematic adaptive step by step design method using the full order sliding surface for mismatched nonlinear systems is presented, Simulation results validate the effectiveness of the proposed control law.展开更多
In this paper,the distributed fuzzy fault-tolerant tracking consensus problem of leader-follower multi-agent systems(MASs)is studied.The objective system includes actuator faults,mismatched parameter uncertainties,non...In this paper,the distributed fuzzy fault-tolerant tracking consensus problem of leader-follower multi-agent systems(MASs)is studied.The objective system includes actuator faults,mismatched parameter uncertainties,nonlinear functions,and exogenous disturbances under switching communication topologies.To solve this problem,a distributed fuzzy fault-tolerant controller is proposed for each follower by adaptive mechanisms to track the state of the leader.Furthermore,the fuzzy logic system is utilized to approximate the unknown nonlinear dynamics.An error estimator is introduced between the mismatched parameter matrix and the input matrix.Then,a selective adaptive law with relative state information is adopted and applied.When calculating the Lyapunov function’s derivative,the coupling terms related to consensus error and mismatched parameter uncertainties can be eliminated.Finally,a numerical simulation is given to validate the effectiveness of the proposed protocol.展开更多
This paper proposes a discrete-time robust control technique for an uncertain nonlinear system. The uncertainty mainly affects the system dynamics due to mismatched parameter variation which is bounded by a predefined...This paper proposes a discrete-time robust control technique for an uncertain nonlinear system. The uncertainty mainly affects the system dynamics due to mismatched parameter variation which is bounded by a predefined known function. In order to compensate the effect of uncertainty, a robust control input is derived by formulating an equivalent optimal control problem for a virtual nominal system with a modified costfunctional. To derive the stabilizing control law for a mismatched system, this paper introduces another control input named as virtual input. This virtual input is not applied directly to stabilize the uncertain system, rather it is used to define a sufficient condition. To solve the nonlinear optimal control problem, a discretetime general Hamilton-Jacobi-Bellman(DT-GHJB) equation is considered and it is approximated numerically through a neural network(NN) implementation. The approximated solution of DTGHJB is used to compute the suboptimal control input for the virtual system. The suboptimal inputs for the virtual system ensure the asymptotic stability of the closed-loop uncertain system. A numerical example is illustrated with simulation results to prove the efficacy of the proposed control algorithm.展开更多
The accurate measurement of parameters such as the cavity-loaded quality factor(Q_(L))and half bandwidth(f_(0.5))is essential for monitoring the performance of superconducting radio-frequency cavities.However,the conv...The accurate measurement of parameters such as the cavity-loaded quality factor(Q_(L))and half bandwidth(f_(0.5))is essential for monitoring the performance of superconducting radio-frequency cavities.However,the conventional"field decay method"employed to calibrate these values requires the cavity to satisfy a"zero-input"condition.This can be challenging when the source impedance is mismatched and produce nonzero forward signals(V_(f))that significantly affect the measurement accuracy.To address this limitation,we developed a modified version of the"field decay method"based on the cavity differential equation.The proposed approach enables the precise calibration of f_(0.5) even under mismatch conditions.We tested the proposed approach on the SRF cavities of the Chinese Accelerator-Driven System Front-End Demo Superconducting Linac and compared the results with those obtained from a network analyzer.The two sets of results were consistent,indicating the usefulness of the proposed approach.展开更多
The design of servo controllers for flexible ball screw drives with matched and mismatched disturbances and uncertainties is focused to improve the tracking performance and bandwidth of ball screw drives.A two degrees...The design of servo controllers for flexible ball screw drives with matched and mismatched disturbances and uncertainties is focused to improve the tracking performance and bandwidth of ball screw drives.A two degrees of freedom mass model is established based on the axial vibration characteristics of the transport ball screw,and the controller of an adaptive integral sliding mode is proposed combining the optimal design of state feedback gain matrix K to restrain the vibration and the matched disturbances and uncertainties.Then for the counteraction of the mismatched disturbances and uncertainties,a nonlinear disturbance observer is also developed.The trajectory tracking performance experiments and bandwidth analysis were conducted on experimental setup with the proposed control method.It is proved that the adaptive integral sliding mode controller has a high tracking performance and bandwidth especially for the axial vibration characteristics model of ball screw drives.And the ball screw tracking accuracy also has a considerable improvement with the application of the proposed nonlinear disturbance observer.展开更多
This letter delnonstrates the structure of the passive radar using TV signals. Because the TV signal is a kind of pseudoperiodic signal, the matched filtering of color TV signals would yield high sidelobes which cause...This letter delnonstrates the structure of the passive radar using TV signals. Because the TV signal is a kind of pseudoperiodic signal, the matched filtering of color TV signals would yield high sidelobes which cause the range ambiguity. To overcome this problem, the mismatched filter is proposed to suppress the correlation sidelobcs of matched filtering of TV signals. By utilizing the iteration process, this method could achieve the required peak sidclobc level. The impacts of the noise and target movement on mismatched filtering are also analysed, Simulation results are included to demonstrate the effectiveness of the proposed technique.展开更多
An idealized tri-material assumption is established to describe the constitutive relationship of mismatched welded joints by considering the influence of heat affected zone（HAZ）.The fracture parameters Jand C＊are e...An idealized tri-material assumption is established to describe the constitutive relationship of mismatched welded joints by considering the influence of heat affected zone（HAZ）.The fracture parameters Jand C＊are estimated for mismatched welded joints with HAZ cracks by finite element analysis with ABAQUS.A middle crack tension（M（T））specimen is utilized in the analysis for different material properties and geometries of the weldment.The influence of mechanical property and geometry on the fracture parameters Jand C＊of the specimen is discussed for the welded joints with HAZ crack.The results suggest that the HAZ property is a significant factor in the estimation of Jand C＊for the mismatched welded joint with HAZ crack.展开更多
Based on the scatter matrix of the four-port lossless mismatched circulator, the phase differential equation of the injection-locked magnetron is derived by comparing different effects of the mismatched and perfect ci...Based on the scatter matrix of the four-port lossless mismatched circulator, the phase differential equation of the injection-locked magnetron is derived by comparing different effects of the mismatched and perfect circulator on the injection ratio. Besides, the locking range of the injection-locked magnetron with the mismatched circulator is deduced by functional operation. In addition, the phase differential equation and the locked bandwidth of the injection-locked system with a mismatched circulator are compared with those of the small injection-ratio case with a perfect circulator. The in- fluence of the circulator reflection coefficient on the injection-locked magnetron is also analyzed by numerical calculation. Theoretical analysis shows that the decrement of the locked bandwidth is less than 1% and decrement of the stable phase difference is less than 1.2% when the reflection coefficient is less than 0.1.展开更多
Metal-on-metal hip resurfacing has gained popularity as a feasible treatment option for young and active patients with hip osteoarthritis and high functional expectations.This procedure should only be performed by sur...Metal-on-metal hip resurfacing has gained popularity as a feasible treatment option for young and active patients with hip osteoarthritis and high functional expectations.This procedure should only be performed by surgeons who have trained specifically in this technique.Preoperative planning is essential for hip resurfacing in order to execute a successful operation and preview any technical problems.The authors present a case of a man who underwent a resurfacing arthroplasty for osteoarthritis of the left hip that was complicated by mismatched implant components that were revised three days afterwards for severe pain and leg length discrepancy.Such mistakes,although rare,can be prevented by educating operating room staff in the size and colour code tables provided by the companies on their prostheses or implant boxes.展开更多
A two-layer switching architecture and a two-layer switching rule for stabilization of switched linear control systems are proposed, under which the mismatched switching between switched systems and their candidate hy...A two-layer switching architecture and a two-layer switching rule for stabilization of switched linear control systems are proposed, under which the mismatched switching between switched systems and their candidate hybrid controllers can be allowed. In the low layer, a state-dependent switching rule with a dwell time constraint to exponentially stabilize switched linear systems is given; in the high layer, supervisory conditions on the mismatched switching frequency and the mismatched switching ratio are presented, under which the closed-loop switched system is still exponentially stable in case of the candidate controller switches delay with respect to the subsystems. Different from the traditional switching rule, the two-layer switching architecture and switching rule have robustness, which in some extend permit mismatched switching between switched subsystems and their candidate controllers.展开更多
The paper presents finite element modeling of crack tip blunting for numerical estimation of fracture parameter of a Mode I crack, in weak alloy steel, which is near and normal to the interface of elastically identica...The paper presents finite element modeling of crack tip blunting for numerical estimation of fracture parameter of a Mode I crack, in weak alloy steel, which is near and normal to the interface of elastically identical but stronger maraging steel. The bimetallic body is subjected to monotonic load in K dominated regime. Crack tip yield zone across the interface, treated as Dugdale’s cohesive zone, is isolated from the bimetallic domain and is modeled alone under the action of respective cohesive stress over yield zones for obtaining the contribution of mismatch between yield strength of the steels in crack energy release rate component, Jinterface. Effect of far field load on Jinterface is found separately from a theoretical model. Numerical and theoretical results of Jinterface are in good agreement.展开更多
Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
Study of radiation properties of mismatched microstrip termination is carried out in warm ionized electron plasma medium. Linearised hydrodynamic theory coupled with vector wave technique is used to investigate radiat...Study of radiation properties of mismatched microstrip termination is carried out in warm ionized electron plasma medium. Linearised hydrodynamic theory coupled with vector wave technique is used to investigate radiation patterns and radiated power of a microstrip mismatched termination in one component electron plasma media for different plasma to source frequencies .These properties are used to compare the performance of an open circuit discontinuity with those of matched microstrip termination. Matched terminations are found more suitable for applications at higher frequencies than an open circuit discontinuity in the plasma medium though in free space they are less suitable.展开更多
基金supported by the Natural Science Foundation of Hubei Province(2021CFA081)the Fundamental Research Funds for the Central Universities(2042023kf0210)the National Natural Science Foundation of China(42277160).
文摘A partly clumped-particles combined with joint planes model was developed to simulate the microstructure of quartz mica schist.It considers grain-scale heterogeneity including microgeometry heterogeneity and grain-scale elastic heterogeneity.Clumped-particles with larger volume and larger stiffness were used to represent stiff minerals such as quartz,the rest of unclumped particles with smaller stiffness were used to represent soft minerals such as mica.The joint planes,which have smaller stiffness and strength than mica,were used to describe schist.The extensive sensitivity studies have shown that the clump’s radius,clump’s content and joint plane’s strength affect the microscopic and macroscopic behaviors of sample.For DanBa quartz mica schist,the model calibrated uniaxial tests and well matched with the stress-strain curves,crack initiation stress and crack damage stress of laboratory test.
文摘BACKGROUND Mismatch repair deficient/microsatellite instability-high(MMR-D/MSI-H)colorectal cancers(CRCs)possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient(MMR-P)or microsatellite stable(MSS)counterparts.CRCs have several prognostic factors,including stage,tumor differentiation,location,lymphovascular and perineural invasion,tumor budding,tumor infiltrating lymphocytes,lymph node yield(LNY),and lymph node ratio(LNR).AIM To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs.METHODS This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment.Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides.MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing.RESULTS Of the 223 patients in our study,87(39.01%)were MMR-D/MSI-H CRCs while 136(60.99%)were MMR-P/MSS CRCs.The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors,including location,stage,tumor budding,lymphovascular and perineural invasion,lymphocytic response,LNY,LNR,and size of uninvolved lymph nodes.LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group(P=0.003 and P<0.001,respectively).Also,the interquartile range of the largest uninvolved lymph node was 1 cm(0.8 cm-1.2 cm)in MMR-D/MSI-H CRCs compared to 0.7 cm(0.6 cm-0.97 cm)in MMRP/MSS CRCs.The overall survival for the MMR-P/MSS CRC group was 71%at five years,and the MMR-D/MSIH CRC group was 92%at five years(P<0.001).CONCLUSION MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics,including an enhanced immune response.This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.
基金supported by The National Key Research and Development Program of China(Grant no.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant no.K-20230085)+5 种基金Post-doctoral Innovative Talent Support Program(Grant no.BX2023375)Lingyan Project of Zhejiang Provincial Department of Science and Technology(Grant no.2025C02059)the National Natural Science Foundation of China(Grant nos.82304946,82473489,and 82403546)Natural Science Foundation of Zhejiang Province(Grant nos.LR21H280001,LGF22H160056,ZCLQN25H1602,and LMS25H160006)Medicine and Health Science Fund of Zhejiang Province Health Commission(Grant nos.2025KY047 and 2022KY658)Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission(Grant no.2022ZA023).
文摘Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.
文摘BACKGROUND Colorectal cancer is one of the malignant tumors with a high incidence and mortality rate globally,and the occurrence of liver metastasis significantly affects patient survival prognosis.In recent years,the application of immune checkpoint inhibitors(ICIs)in cancer treatment has made important progress,especially showing good therapeutic effects in patients with high microsatellite instability or mismatch repair deficiency.However,for the majority of patients with microsatellite stable(MSS)or proficient mismatch repair(pMMR)colorectal cancer,the efficacy of ICIs is limited,prompting researchers to explore combination therapy strategies to improve efficacy.Targeted drugs such as tyrosine kinase inhibitors(TKIs)and radiotherapy are believed to work synergistically with ICIs by modifying the tumor microenvironment and enhancing antigen presentation.AIM To investigate the efficacy and safety of the combination therapy of radiotherapy,ICIs,and TKIs in patients with MSS or pMMR colorectal cancer liver metastasis(CCLM),in order to provide new clinical treatment references.METHODS A retrospective analysis was conducted on the clinical data of 43 MSS or pMMR CCLM patients treated at our hospital from September 2021 to July 2024.Based on the treatment interventions received,the patients were divided into a control group(n=21,receiving ICIs and TKIs combination therapy)and an observation group(n=22,receiving radiotherapy,ICIs,and TKIs triple therapy).The therapeutic effects,serum tumor markers(carcinoembryonic antigen and RESULTS The disease control rate in the observation group(63.64%)was significantly higher than that of the control group(23.81%)(P<0.05)).Both groups showed a decrease in carcinoembryonic antigen and carbohydrate antigen 199 levels post-treatment,with the observation group demonstrating a more significant change(P<0.05).The median progression-free survival and median overall survival in the control group were 5.1 months and 7.6 months,respectively,while the observation group had a median progression-free survival and overall survival of 4.3 months and 6.9 months,respectively.The control group had longer survival times than the observation group,but the differences were not statistically significant(P>0.05).The incidence of adverse reactions,including nausea and vomiting,gastrointestinal reactions,skin reactions,bone marrow suppression,liver and kidney function impairment,neurotoxicity,leukopenia,neutropenia,and thrombocytopenia,showed no significant differences between the two groups(P>0.05).CONCLUSION Compared to the ICIs and TKIs combination therapy,the radiotherapy,ICIs,and TKIs triple therapy can further improve the disease control rate and serum tumor marker levels in MSS or pMMR CCLM patients without increasing the risk of related adverse reactions,making it a treatment regimen worthy of further validation.
文摘Welding of high strength low alloy steels (HSLA) involves usage of low, even and high strength filler materials (electrodes) than the parent material depending on the application of the welded structures and the availability of the filler material. In the present investigation, the fatigue crack growth behaviour of weld metal (WM) and heat affected zone (HAZ) regions of under matched (UM), equal matched (EM) and over matched (OM) joints has been studied. The base material used in this investigation is HSLA-80 steel of weldable grade. Shielded metal arc welding (SMAW) process has been used to fabricate the butt joints. Centre cracked tension (CCT) specimen has been used to evaluate the fatigue crack growth behaviour of the welded joints. Fatigue crack growth experiments have been conducted using servo hydraulic controlled fatigue testing machine at constant amplitude loading (R=0).A method has been proposed to predict the fatigue life of HSLA steel welds using fracture mechanics approach by incorporating influences of mismatch ratio (MMR) and notch location.
文摘In this paper, an adaptive full order sliding mode （FOSM） controller is proposed for strict feedback nonlinear systems with mismatched uncertainties. The design objective of the controller is to track a specified trajectory in presence of significant mismatched uncertainties. In the first step the dynamic model for the first state is considered by the desired tracking signal. After the first step the desired dynamic model for each state is defined by the previous one. An adaptive tuning law is developed for the FOSM controller to deal with the bounded system uncertainty. The major advantages offered by this adaptive FOSM controller are that advanced knowledge about the upper bound of the system uncertainties is not a necessary requirement and the proposed method is an effective solution for the chattering elimination from the control signal. The controller is designed considering the full-order sliding surface. System robustness and the stability of the controller are proved by using the Lyapunov technique. A systematic adaptive step by step design method using the full order sliding surface for mismatched nonlinear systems is presented, Simulation results validate the effectiveness of the proposed control law.
基金This work was supported by Tianjin Natural Science Foundation of China(20JCYBJC01060,20JCQNJC01450)the National Natural Science Foundation of China(61973175)Tianjin Postgraduate Scientific Research and Innovation Project(2020YJSZXB03,2020YJSZXB12).
文摘In this paper,the distributed fuzzy fault-tolerant tracking consensus problem of leader-follower multi-agent systems(MASs)is studied.The objective system includes actuator faults,mismatched parameter uncertainties,nonlinear functions,and exogenous disturbances under switching communication topologies.To solve this problem,a distributed fuzzy fault-tolerant controller is proposed for each follower by adaptive mechanisms to track the state of the leader.Furthermore,the fuzzy logic system is utilized to approximate the unknown nonlinear dynamics.An error estimator is introduced between the mismatched parameter matrix and the input matrix.Then,a selective adaptive law with relative state information is adopted and applied.When calculating the Lyapunov function’s derivative,the coupling terms related to consensus error and mismatched parameter uncertainties can be eliminated.Finally,a numerical simulation is given to validate the effectiveness of the proposed protocol.
文摘This paper proposes a discrete-time robust control technique for an uncertain nonlinear system. The uncertainty mainly affects the system dynamics due to mismatched parameter variation which is bounded by a predefined known function. In order to compensate the effect of uncertainty, a robust control input is derived by formulating an equivalent optimal control problem for a virtual nominal system with a modified costfunctional. To derive the stabilizing control law for a mismatched system, this paper introduces another control input named as virtual input. This virtual input is not applied directly to stabilize the uncertain system, rather it is used to define a sufficient condition. To solve the nonlinear optimal control problem, a discretetime general Hamilton-Jacobi-Bellman(DT-GHJB) equation is considered and it is approximated numerically through a neural network(NN) implementation. The approximated solution of DTGHJB is used to compute the suboptimal control input for the virtual system. The suboptimal inputs for the virtual system ensure the asymptotic stability of the closed-loop uncertain system. A numerical example is illustrated with simulation results to prove the efficacy of the proposed control algorithm.
基金supported by the project of Large Research Infrastructures"China initiative Accelerator-Driven System"(No.2017-000052-75-01-000590)"Studies of intelligent LLRF control algorithms for superconducting RF cavities"(No.E129851YR0)the National Natural Science Foundation of China(No.12205344).
文摘The accurate measurement of parameters such as the cavity-loaded quality factor(Q_(L))and half bandwidth(f_(0.5))is essential for monitoring the performance of superconducting radio-frequency cavities.However,the conventional"field decay method"employed to calibrate these values requires the cavity to satisfy a"zero-input"condition.This can be challenging when the source impedance is mismatched and produce nonzero forward signals(V_(f))that significantly affect the measurement accuracy.To address this limitation,we developed a modified version of the"field decay method"based on the cavity differential equation.The proposed approach enables the precise calibration of f_(0.5) even under mismatch conditions.We tested the proposed approach on the SRF cavities of the Chinese Accelerator-Driven System Front-End Demo Superconducting Linac and compared the results with those obtained from a network analyzer.The two sets of results were consistent,indicating the usefulness of the proposed approach.
基金Project(2013ZX04008011)supported by the National Science and Technology Major Projects of ChinaProject(51675100)supported by the National Natural Science Foundation of China
文摘The design of servo controllers for flexible ball screw drives with matched and mismatched disturbances and uncertainties is focused to improve the tracking performance and bandwidth of ball screw drives.A two degrees of freedom mass model is established based on the axial vibration characteristics of the transport ball screw,and the controller of an adaptive integral sliding mode is proposed combining the optimal design of state feedback gain matrix K to restrain the vibration and the matched disturbances and uncertainties.Then for the counteraction of the mismatched disturbances and uncertainties,a nonlinear disturbance observer is also developed.The trajectory tracking performance experiments and bandwidth analysis were conducted on experimental setup with the proposed control method.It is proved that the adaptive integral sliding mode controller has a high tracking performance and bandwidth especially for the axial vibration characteristics model of ball screw drives.And the ball screw tracking accuracy also has a considerable improvement with the application of the proposed nonlinear disturbance observer.
文摘This letter delnonstrates the structure of the passive radar using TV signals. Because the TV signal is a kind of pseudoperiodic signal, the matched filtering of color TV signals would yield high sidelobes which cause the range ambiguity. To overcome this problem, the mismatched filter is proposed to suppress the correlation sidelobcs of matched filtering of TV signals. By utilizing the iteration process, this method could achieve the required peak sidclobc level. The impacts of the noise and target movement on mismatched filtering are also analysed, Simulation results are included to demonstrate the effectiveness of the proposed technique.
基金Sponsored by National High Technology Research and Development Program of China(2012AA040106)
文摘An idealized tri-material assumption is established to describe the constitutive relationship of mismatched welded joints by considering the influence of heat affected zone（HAZ）.The fracture parameters Jand C＊are estimated for mismatched welded joints with HAZ cracks by finite element analysis with ABAQUS.A middle crack tension（M（T））specimen is utilized in the analysis for different material properties and geometries of the weldment.The influence of mechanical property and geometry on the fracture parameters Jand C＊of the specimen is discussed for the welded joints with HAZ crack.The results suggest that the HAZ property is a significant factor in the estimation of Jand C＊for the mismatched welded joint with HAZ crack.
基金Project supported by the National Basic Research Program of China(Grant No.2013CB328901)the National Natural Science Foundation of China(Grant No.11305177)
文摘Based on the scatter matrix of the four-port lossless mismatched circulator, the phase differential equation of the injection-locked magnetron is derived by comparing different effects of the mismatched and perfect circulator on the injection ratio. Besides, the locking range of the injection-locked magnetron with the mismatched circulator is deduced by functional operation. In addition, the phase differential equation and the locked bandwidth of the injection-locked system with a mismatched circulator are compared with those of the small injection-ratio case with a perfect circulator. The in- fluence of the circulator reflection coefficient on the injection-locked magnetron is also analyzed by numerical calculation. Theoretical analysis shows that the decrement of the locked bandwidth is less than 1% and decrement of the stable phase difference is less than 1.2% when the reflection coefficient is less than 0.1.
文摘Metal-on-metal hip resurfacing has gained popularity as a feasible treatment option for young and active patients with hip osteoarthritis and high functional expectations.This procedure should only be performed by surgeons who have trained specifically in this technique.Preoperative planning is essential for hip resurfacing in order to execute a successful operation and preview any technical problems.The authors present a case of a man who underwent a resurfacing arthroplasty for osteoarthritis of the left hip that was complicated by mismatched implant components that were revised three days afterwards for severe pain and leg length discrepancy.Such mistakes,although rare,can be prevented by educating operating room staff in the size and colour code tables provided by the companies on their prostheses or implant boxes.
基金This work was supported by the National Natural Science Foundation of China （51307076）, and the Provincial Natural Science Foundation of Liaoning （201602350）.
基金supported by the National Natural Science Foundation of China(No.61233002)the Fundamental Research Funds for the Central Universities(No.N120404019)
文摘A two-layer switching architecture and a two-layer switching rule for stabilization of switched linear control systems are proposed, under which the mismatched switching between switched systems and their candidate hybrid controllers can be allowed. In the low layer, a state-dependent switching rule with a dwell time constraint to exponentially stabilize switched linear systems is given; in the high layer, supervisory conditions on the mismatched switching frequency and the mismatched switching ratio are presented, under which the closed-loop switched system is still exponentially stable in case of the candidate controller switches delay with respect to the subsystems. Different from the traditional switching rule, the two-layer switching architecture and switching rule have robustness, which in some extend permit mismatched switching between switched subsystems and their candidate controllers.
文摘The paper presents finite element modeling of crack tip blunting for numerical estimation of fracture parameter of a Mode I crack, in weak alloy steel, which is near and normal to the interface of elastically identical but stronger maraging steel. The bimetallic body is subjected to monotonic load in K dominated regime. Crack tip yield zone across the interface, treated as Dugdale’s cohesive zone, is isolated from the bimetallic domain and is modeled alone under the action of respective cohesive stress over yield zones for obtaining the contribution of mismatch between yield strength of the steels in crack energy release rate component, Jinterface. Effect of far field load on Jinterface is found separately from a theoretical model. Numerical and theoretical results of Jinterface are in good agreement.
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
文摘Study of radiation properties of mismatched microstrip termination is carried out in warm ionized electron plasma medium. Linearised hydrodynamic theory coupled with vector wave technique is used to investigate radiation patterns and radiated power of a microstrip mismatched termination in one component electron plasma media for different plasma to source frequencies .These properties are used to compare the performance of an open circuit discontinuity with those of matched microstrip termination. Matched terminations are found more suitable for applications at higher frequencies than an open circuit discontinuity in the plasma medium though in free space they are less suitable.
