BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-imm...BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.展开更多
BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing f...BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.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
The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed...The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed an evaluation indicator system and used the methods of gravity center model,spatial mismatch index model and obstacle degree model to calculate the spatial mismatch index and influencing factors of ice and snow tourism resources and tourism economy in Altay region as a whole and in each county and city.It found in the study period:(i)the ice and snow tourism resources and tourism economy in Altay region was synchronous in the development of time sequence,while the spatial distribution pattern was characterized by regional imbalance;(ii)at the macro scale,the spatial mismatch degree of the ice-snow tourism resource center and the tourism economic center in Altay region was gradually reduced,but they were always separated from the spatial geometric center of Altay region;(iii)at the micro scale,the spatial mismatch index of counties and cities in Altay region was mainly negative mismatch,and the types of spatial mismatch changed in different degrees;(iv)the factors showed certain spatial differentiation characteristics in different counties of Altay region,and there were some differences in the obstacles of different mismatch level areas,and the economic basis was the most frequent obstacle in different mismatch level areas of Altay region.展开更多
Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phas...Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.展开更多
In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile str...In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile strength of the joints reduces 32%,53% and 59%,when the mismatch of the joint was 0. 635 mm,1. 44 mm,1. 83 mm,respectively.Incomplete penetration,additional bending moment( Ma) and decrease of effective load region area are considered to explain this phenomenon. The fracture location of tensile specimens occurred at the weld zone( WZ) close to partial melt zone( PMZ),corresponding to a sharp decline of microhardness from PMZ to WZ. The original position of fracture is found at weld toe,where incomplete penetration forms due to the introduction of gradient mismatches.展开更多
The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of ar...The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of arrival (DOA) mismatch and the mismatches arising from array disturbance, are studied, respectively. To obtain the effective methods for compensating for the system mismatches, we analyze the performance of the improved LC-GSC with the diagonal loading and additional constraints (such as the directional constraints and derivative constraints). The computer simulations show that the techniques of diagonal loading and additional constraints can effectively compensate for the system mismatches. The loss of array gains can be controlled within 3 dB in the presence of 20% of array disturbances or DOA mismatch when the signal-to-noise ratio is less than 10 dB. The analysis illustrates that the proposed compensation methods are valid and feasible.展开更多
G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Ram...G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Raman spectral characterization of Polyadenylic acid (PolyA), Polyguanylic acid (PolyG) and their equimolar mixture in solution of 0.08 mol/L Na^+, pH7.0. The experiment showed the following three results. (1) At the experimental conditions used in the present work, PolyA and G A complexes existed as single-stranded and double-stranded helix of A form, respectively. And PolyG mainly occurred to be anti-parallel quadruplex conformers. (2) The formation of G A complexes, on one hand strengthened parts of base stacking interactions especially for PolyG, leading to Raman hypochromism effect with some corresponding bands shifting, and on the other hand weakened other base stacking interactions especially for PolyA to a certain degree. During this process, the backbone of PolyG underwent a significant change, but PolyA still conserved its main chain conformation. (3) The formation of G A complexes was stabilized by two interbase hydrogen- bond interactions (i.e. N6H2(A)-N3 (G) and N7 (A)--N2H2(G)) and a third hydrogen bond between O2^+ (G) and N6 (A). The third hydrogen bond was responsible for the remarkable changes of PolyG backbone conformation.展开更多
Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood h...Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood has been shown to impact discourse processing. In these studies, a strong expectancy was evoked by a linguistic context. In the present study, a strong expectancy was induced by a visual (non-linguistic) context paired with a sentence. A spatial array was followed by a sentence that matched (□○—The square stands in front of the circle) or mismatched the picture (intra-dimensional mismatch: □○—The square stands behind the circle;extra-dimensional mismatch: □○—The square stands above the circle). The main question was whether mood effects on the processing of visually induced expectancies are similar or different from mood effects on the processing of linguistically induced expectancies. To this aim, we presented conceptual (mis)matches that differed in saliency: intra-dimensional vs. extra-dimensional mismatches which are both reported to elicit an N2b/N400 and P600, reflecting reanalysis. EEG was recorded while participants read for comprehension. Mood (happy vs. sad) was effectively induced by film clips. Neither for N2b/N400 nor for P600, an interaction between mood and match was observed. Thus, in contrast with studies investigating the effects of pure linguistic mismatches (linguistic context paired with unexpected lexical item), mood did not modulate the processing of conceptual mismatches. However, a main effect of match revealed different ERP patterns for the two mismatches. While an increase in N2b/ N400 occurred for the intra-dimensional and extra-dimensional mismatches, a P600 only occurred to the extra-dimensional (more salient) mismatches. This finding is taken as support that being in an emotional state (positive or negative mood) influences processes of reanalysis. That is, when being in an emotional state, a reanalysis (monitoring) process is exclusively triggered by salient mismatches.展开更多
A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, w...A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, which include the capacitor mismatches and residue amplifier distortion, are extracted integrally. A modified 1st pipelined stage is adopted to solve the signal overflow caused by the Pseudo-random Noise (PN) sequences. Behavioral simulation results verify the effectiveness of the algorithm. It improves the Signal-to-Noise-plus-Distortion Ratio (SNDR) and Spurious-Free-Dynamic-Range (SFDR) of the pipelined ADC from 41.8 dB to 78.3 dB and 55.6 dB to 98.6 dB, respectively, which is comparable to the prior arts.展开更多
A low hole injection efficiency for InGaN/GaN micro-light-emitting diodes(μLEDs) has become one of the main bottlenecks affecting the improvement of the external quantum efficiency(EQE) and the optical power. In this...A low hole injection efficiency for InGaN/GaN micro-light-emitting diodes(μLEDs) has become one of the main bottlenecks affecting the improvement of the external quantum efficiency(EQE) and the optical power. In this work, we propose and fabricate a polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure for 445 nm GaN-based μLEDs with the size of 40 × 40 μm^(2), which serves as the hole injection layer. The polarization-induced electric field in the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure provides holes with more energy and can facilitate the non-equilibrium holes to transport into the active region for radiative recombination. Meanwhile, a secondary etched mesa for μLEDs is also designed, which can effectively keep the holes apart from the defected region of the mesa sidewalls, and the surface nonradiative recombination can be suppressed. Therefore, the proposed μLED with the secondary etched mesa and the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure has the enhanced EQE and the improved optical power density when compared with the μLED without such designs.展开更多
Aiming at the problem of detecting a distributed target when signal mismatch occurs,this paper proposes a tunable detector parameterized by an adjustable parameter.By adjusting the parameter,the tunable detector can a...Aiming at the problem of detecting a distributed target when signal mismatch occurs,this paper proposes a tunable detector parameterized by an adjustable parameter.By adjusting the parameter,the tunable detector can achieve robust or selective detection of mismatched signals.Moreover,the proposed tunable detector,with a proper tunable parameter,can provide higher detection probability compared with existing detectors in the case of no signal mismatch.In addition,the proposed tunable detector possesses the constant false alarm rate property with the unknown noise covariance matrix.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
BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dys...BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.展开更多
基金Supported by Ministerio de la Produccion de Peru,No.317-PNICP-EC-2014,and No.430-PNICP-PIAP-2014Consejo Nacional de Ciencia Tecnologia e Innovacion Tecnologica,No.196-2015-FONDECYT,No.197-2015-FONDECYT,and No.204-2015-FONDECYT.
文摘BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
基金Supported by National High Level Hospital Clinical Research Funding,No.2023-NHLHCRF-YYPPLC-TJ-03.
文摘BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.
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The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed an evaluation indicator system and used the methods of gravity center model,spatial mismatch index model and obstacle degree model to calculate the spatial mismatch index and influencing factors of ice and snow tourism resources and tourism economy in Altay region as a whole and in each county and city.It found in the study period:(i)the ice and snow tourism resources and tourism economy in Altay region was synchronous in the development of time sequence,while the spatial distribution pattern was characterized by regional imbalance;(ii)at the macro scale,the spatial mismatch degree of the ice-snow tourism resource center and the tourism economic center in Altay region was gradually reduced,but they were always separated from the spatial geometric center of Altay region;(iii)at the micro scale,the spatial mismatch index of counties and cities in Altay region was mainly negative mismatch,and the types of spatial mismatch changed in different degrees;(iv)the factors showed certain spatial differentiation characteristics in different counties of Altay region,and there were some differences in the obstacles of different mismatch level areas,and the economic basis was the most frequent obstacle in different mismatch level areas of Altay region.
基金supported in part by the National Natural Science Founda⁃tion of China(NSFC)under Grant Nos.62301148,62341107,and 62261160576by the Natural Science Foundation of Jiangsu Prov⁃ince under Grant No.BK20230824in part by the Key Technologies R&D Program of Jiangsu(Prospective and Key Technologies for Indus⁃try)under Grant Nos.BE2023022 and BE2023022-1.
文摘Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.
基金supported by the National Natural Science Foundation of China(No.50904020)the Fundamental Research Funds for the Central Universities(No.HIT.NSRIF.2012007)
文摘In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile strength of the joints reduces 32%,53% and 59%,when the mismatch of the joint was 0. 635 mm,1. 44 mm,1. 83 mm,respectively.Incomplete penetration,additional bending moment( Ma) and decrease of effective load region area are considered to explain this phenomenon. The fracture location of tensile specimens occurred at the weld zone( WZ) close to partial melt zone( PMZ),corresponding to a sharp decline of microhardness from PMZ to WZ. The original position of fracture is found at weld toe,where incomplete penetration forms due to the introduction of gradient mismatches.
基金supported by the Aviation Science Foundation of China under Grant No. 20112080014
文摘The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller (LC-GSC) is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of arrival (DOA) mismatch and the mismatches arising from array disturbance, are studied, respectively. To obtain the effective methods for compensating for the system mismatches, we analyze the performance of the improved LC-GSC with the diagonal loading and additional constraints (such as the directional constraints and derivative constraints). The computer simulations show that the techniques of diagonal loading and additional constraints can effectively compensate for the system mismatches. The loss of array gains can be controlled within 3 dB in the presence of 20% of array disturbances or DOA mismatch when the signal-to-noise ratio is less than 10 dB. The analysis illustrates that the proposed compensation methods are valid and feasible.
基金Project supported by the Natural Science Foundation of Guangdong Province, China (Grant No 021093) and Key-stone Science and Technology Foundation of Guangdong Province, China (Grant No 2KM04502S).
文摘G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Raman spectral characterization of Polyadenylic acid (PolyA), Polyguanylic acid (PolyG) and their equimolar mixture in solution of 0.08 mol/L Na^+, pH7.0. The experiment showed the following three results. (1) At the experimental conditions used in the present work, PolyA and G A complexes existed as single-stranded and double-stranded helix of A form, respectively. And PolyG mainly occurred to be anti-parallel quadruplex conformers. (2) The formation of G A complexes, on one hand strengthened parts of base stacking interactions especially for PolyG, leading to Raman hypochromism effect with some corresponding bands shifting, and on the other hand weakened other base stacking interactions especially for PolyA to a certain degree. During this process, the backbone of PolyG underwent a significant change, but PolyA still conserved its main chain conformation. (3) The formation of G A complexes was stabilized by two interbase hydrogen- bond interactions (i.e. N6H2(A)-N3 (G) and N7 (A)--N2H2(G)) and a third hydrogen bond between O2^+ (G) and N6 (A). The third hydrogen bond was responsible for the remarkable changes of PolyG backbone conformation.
文摘Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood has been shown to impact discourse processing. In these studies, a strong expectancy was evoked by a linguistic context. In the present study, a strong expectancy was induced by a visual (non-linguistic) context paired with a sentence. A spatial array was followed by a sentence that matched (□○—The square stands in front of the circle) or mismatched the picture (intra-dimensional mismatch: □○—The square stands behind the circle;extra-dimensional mismatch: □○—The square stands above the circle). The main question was whether mood effects on the processing of visually induced expectancies are similar or different from mood effects on the processing of linguistically induced expectancies. To this aim, we presented conceptual (mis)matches that differed in saliency: intra-dimensional vs. extra-dimensional mismatches which are both reported to elicit an N2b/N400 and P600, reflecting reanalysis. EEG was recorded while participants read for comprehension. Mood (happy vs. sad) was effectively induced by film clips. Neither for N2b/N400 nor for P600, an interaction between mood and match was observed. Thus, in contrast with studies investigating the effects of pure linguistic mismatches (linguistic context paired with unexpected lexical item), mood did not modulate the processing of conceptual mismatches. However, a main effect of match revealed different ERP patterns for the two mismatches. While an increase in N2b/ N400 occurred for the intra-dimensional and extra-dimensional mismatches, a P600 only occurred to the extra-dimensional (more salient) mismatches. This finding is taken as support that being in an emotional state (positive or negative mood) influences processes of reanalysis. That is, when being in an emotional state, a reanalysis (monitoring) process is exclusively triggered by salient mismatches.
基金Supported by the Doctoral Program Foundation of Institutions of Higher Education of China (No.20120111120008)State Key Lab of ASIC & System(Fudan University) (No. 11KF001)Special Fund for Doctoral Program (Hefei University of Technology) (No.2011HGBZ0953)
文摘A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, which include the capacitor mismatches and residue amplifier distortion, are extracted integrally. A modified 1st pipelined stage is adopted to solve the signal overflow caused by the Pseudo-random Noise (PN) sequences. Behavioral simulation results verify the effectiveness of the algorithm. It improves the Signal-to-Noise-plus-Distortion Ratio (SNDR) and Spurious-Free-Dynamic-Range (SFDR) of the pipelined ADC from 41.8 dB to 78.3 dB and 55.6 dB to 98.6 dB, respectively, which is comparable to the prior arts.
基金supported in part by the National Natural Science Foundation of China (Grant Nos.62074050 and 61975051)Research Fund by State Key Laboratory of Reliability and Intelligence of Electrical Equipment,Hebei University of Technology (Grant Nos.EERI PI2020008 and EERI_PD2021012)Joint Research Project for Tunghsu Group and Hebei University of Technology (Grant No.HI1909)。
文摘A low hole injection efficiency for InGaN/GaN micro-light-emitting diodes(μLEDs) has become one of the main bottlenecks affecting the improvement of the external quantum efficiency(EQE) and the optical power. In this work, we propose and fabricate a polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure for 445 nm GaN-based μLEDs with the size of 40 × 40 μm^(2), which serves as the hole injection layer. The polarization-induced electric field in the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure provides holes with more energy and can facilitate the non-equilibrium holes to transport into the active region for radiative recombination. Meanwhile, a secondary etched mesa for μLEDs is also designed, which can effectively keep the holes apart from the defected region of the mesa sidewalls, and the surface nonradiative recombination can be suppressed. Therefore, the proposed μLED with the secondary etched mesa and the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure has the enhanced EQE and the improved optical power density when compared with the μLED without such designs.
基金supported by the National Natural Science Foundation of China(62071482)。
文摘Aiming at the problem of detecting a distributed target when signal mismatch occurs,this paper proposes a tunable detector parameterized by an adjustable parameter.By adjusting the parameter,the tunable detector can achieve robust or selective detection of mismatched signals.Moreover,the proposed tunable detector,with a proper tunable parameter,can provide higher detection probability compared with existing detectors in the case of no signal mismatch.In addition,the proposed tunable detector possesses the constant false alarm rate property with the unknown noise covariance matrix.
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Supported by National Natural Science Foundation of China,No.82172628。
文摘BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.