High microsatellite instability(MSI-H)colorectal cancer(CRC),caused by deficient mismatch repair,accounts for about 15%of all CRC cases and is more common in right-sided tumors.While early-stage MSI-H CRC has a relati...High microsatellite instability(MSI-H)colorectal cancer(CRC),caused by deficient mismatch repair,accounts for about 15%of all CRC cases and is more common in right-sided tumors.While early-stage MSI-H CRC has a relatively good prognosis,advanced cases often respond poorly to standard chemotherapy.Immune checkpoint inhibitors,such as pembrolizumab,have shown strong and lasting effects in MSI-H CRC.Pembrolizumab is now approved as a first-line treatment for metastatic MSI-H CRC due to its superior outcomes compared to traditional chemotherapy.CASE SUMMARY A 44-year-old male with MSI-H transverse colon cancer presented with hematochezia,abdominal pain,and significant weight loss.Imaging revealed a bulky tumor with invasion of adjacent structures and multiple liver lesions.A diverting ileostomy was performed followed by 36 cycles of pembrolizumab.The patient achieved a clinical and radiologic complete response.One month after completing the treatment,the patient underwent laparoscopic right hemicolectomy.A spontaneous transection of the colon at the original tumor site was unexpectedly identified.Final pathology confirmed pathological complete response(ypT0N0)with fibrosis.The patient recovered well after surgery,and follow-up showed no evidence of recurrence.CONCLUSION Immune checkpoint inhibitors may cause delayed structural damage to bowel tissue even after apparent complete tumor regression.展开更多
The influence of the squeeze film between the tube and the support structure on flow-induced vibrations is a critical factor in tube bundles subjected to two-phase cross-flow.This aspect can significantly alter the th...The influence of the squeeze film between the tube and the support structure on flow-induced vibrations is a critical factor in tube bundles subjected to two-phase cross-flow.This aspect can significantly alter the threshold for fluidelastic instability and affect heat transfer efficiency.This paper presents a mathematical model incorporating the squeeze film force between the tube and the support structure.We aim to clarify the mechanisms underlying fluidelastic instability in tube bundle systems exposed to two-phase flow.Using a self-developed computer program,we performed numerical calculations to examine the influence of the squeeze film on the threshold of fluidelastic instability in the tube bundle system.Furthermore,we analyzed how the thickness and length of the squeeze film affect both the underlying mechanisms and the critical velocity of fluidelastic instability.展开更多
We are intrigued by the issues of shock instability,with a particular emphasis on numerical schemes that address the carbuncle phenomenon by reducing dissipation rather than increasing it.For a specific class of plana...We are intrigued by the issues of shock instability,with a particular emphasis on numerical schemes that address the carbuncle phenomenon by reducing dissipation rather than increasing it.For a specific class of planar flow fields where the transverse direction exhibits vanishing but non-zero velocity components,such as a disturbed onedimensional(1D)steady shock wave,we conduct a formal asymptotic analysis for the Euler system and associated numerical methods.This analysis aims to illustrate the discrepancies among various low-dissipative numerical algorithms.Furthermore,a numerical stability analysis of steady shock is undertaken to identify the key factors underlying shock-stable algorithms.To verify the stability mechanism,a consistent,low-dissipation,and shock-stable HLLC-type Riemann solver is presented.展开更多
Self-excited longitudinal combustion instabilities were investigated in a hypergolic liquid bipropellant combustor, which applied single dual-swirl coaxial injector. Hot-fire tests were conducted for four different in...Self-excited longitudinal combustion instabilities were investigated in a hypergolic liquid bipropellant combustor, which applied single dual-swirl coaxial injector. Hot-fire tests were conducted for four different injector geometries, while extensive tests on injection conditions were carried out for each injector geometry. The synchronous measurement of the pressure and heat release rate was applied, successfully capturing the process of the pressure and heat release rate enhanced coupling and developing into in-phase oscillation. By calculating Rayleigh index at the head and middle section of the chamber, it is shown that Rayleigh index of the middle section is even higher than that of the head, indicating a long heat release zone. When the combustion instability occurs, the pressure in propellant manifolds also oscillates with the same frequency and lags behind the oscillation in the combustor. Compared to the oscillation in the outer injector manifold, the oscillation in the inner injector manifold shows a higher correlation with that in the chamber in amplitude and phase. Based on numerical simulations of the multiphase cold flow inside the injector and combustion process in the chamber, it is found that injector geometries affect longitudinal combustion instability by changing spray cone angle. The spray with small cone angle is more sensitive to the modulation of longitudinal pressure wave in combustion simulations, which is more likely to excite the longitudinal combustion instability. Meanwhile, the combustion instability may be related to the pulsating coherent structure generated by the spray fluctuation, which is determined by injection conditions. Besides, a positive feedback closed-loop system associated with the active fluctuation and passive oscillation of the spray is believed to excite and sustain the longitudinal combustion instability.展开更多
The utilization of Inlet Guide Vane (IGV) plays a key factor in affecting the instability evolution. Existing literature mainly focuses on the effect of IGV on instability inception that occurs in the rotor region. Ho...The utilization of Inlet Guide Vane (IGV) plays a key factor in affecting the instability evolution. Existing literature mainly focuses on the effect of IGV on instability inception that occurs in the rotor region. However, with the emergence of compressor instability starting from the stator region, the mechanism of various instability inceptions that occurs in different blade rows due to the change of IGV angles should be further examined. In this study, experiments were focused on three types of instability inceptions observed previously in a 1.5-stage axial flow compressor. To analyze the conversion of stall evolutions, the compressor rotating speed was set to 17 160 r/min, at which both the blade loading in the stator hub region and rotor tip region were close to the critical value before final compressor stall. Meanwhile, the dynamic test points with high-response were placed to monitor the pressures both at the stator trailing edges and rotor tips. The results indicate that the variation of reaction determines the region where initial instability occurs. Indeed, negative pre-rotation of the inlet guide vane leads to high-reaction, initiating stall disturbance from the rotor region. Positive pre-rotation results in low-reaction, initiating stall disturbance from the stator region. Furthermore, the type of instability evolution is affected by the radial loading distribution under different IGV angles. Specifically, a spike-type inception occurs at the rotor blade tip with a large angle of attack at the rotor inlet (−2°, −4° and −6°). Meanwhile, the critical total pressure ratio at the rotor tip is 1.40 near stall. As the angle of attack decreases, the stator blade loading reaches its critical boundary, with a value of approximately 1.35. At this moment, if the rotor tip maintains high blade loading similar to the stator hub, the partial surge occurs (0° and +2°);otherwise, the hub instability occurs (+4° and +6°).展开更多
In order to calculate the multipoles in real materials with considerable intersite Coulomb interaction V,we develop a self-consistent program which starts from the frst-principles calculations to solve the tight-bindi...In order to calculate the multipoles in real materials with considerable intersite Coulomb interaction V,we develop a self-consistent program which starts from the frst-principles calculations to solve the tight-binding Hamiltonian including onsite Coulomb repulsion U,V,and spin-orbital couplingλ.The program is applied to Ba_(2)MgReO_(6)to fgure out the mechanism of structural instability and magnetic ordering.A comprehensive quadrupole phase diagram versus U and V withλ=0.28 eV is calculated.Our results demonstrate that the easy-plane anisotropy and the intersite Coulomb repulsion V must be considered to remove the orbital frustration.The increase of V to>20 meV would arrange quadrupole Q_(x^(2)-y^(2))antiparallelly,accompanied by small parallel Q_(3z)^(2)-r^(2),and stabilize Ba_(2)MgReO_(6)into the body-centered tetragonal structure.Such antiparallel Q_(x^(2)-y^(2))provides a new mechanism for the Dzyaloshinskii-Moriya interaction and gives rise to the canted antiferromagnetic(CAF)state along the[110]axis.Moreover,sizable octupoles such as O_(21)^(31),O_(21)^(33),O_(21)^(34)and O_(21)^(36)are discovered for the frst time in the CAF state.Our study not only provides a comprehensive understanding of the experimental results in Ba_(2)MgReO_(6),but also serves as a general and useful tool for the study of multipole physics in 5d compounds.展开更多
The effect of drive laser wavelength on the growth of ablative Rayleigh–Taylor instability(ARTI)in inertial confinemen fusion(ICF)is studied with two-dimensional numerical simulations.The results show that in the pla...The effect of drive laser wavelength on the growth of ablative Rayleigh–Taylor instability(ARTI)in inertial confinemen fusion(ICF)is studied with two-dimensional numerical simulations.The results show that in the plasma acceleration phase,shorter wavelengths lead to more efficien coupling between the laser and the kinetic energy of the implosion fluid Under the condition that the laser energy coupled to the implosion flui is constant,the ARTI growth rate decreases as the laser wavelength moves toward the extreme ultraviolet band,reaching its minimum value near λ=65 nm,and when the laser wavelength continuously moves toward the X-ray band,the ARTI growth rate increases rapidly.It is found that the results deviate from the theoretical ARTI growth rate.As the laser intensity benchmark increases,the position of the minimum ARTI growth rate shifts toward shorter wavelengths.As the initial sinusoidal perturbation wavenumber decreases,the position of the minimum ARTI growth rate shifts toward longer wavelengths.We believe that the conclusions drawn from the present simulations and analysis will help provide a better understanding of the ICF process and improve the theory of ARTI growth.展开更多
Hydrodynamic instability growth at the deuterium-tritium(DT)fuel-ablator interface plays a critical role in determining the performance of inertial confinement fusion implosions.During the late stages of implosion,ins...Hydrodynamic instability growth at the deuterium-tritium(DT)fuel-ablator interface plays a critical role in determining the performance of inertial confinement fusion implosions.During the late stages of implosion,insufficient doping of the ablator material can result in highenergy X-ray preheat,which may trigger the development of a classical-like Rayleigh-Taylor instability(RTI)at the fuel-ablator interface.In implosion experiments at the Shenguang 100 kJ-level laser facility,the primary source of perturbation is the roughness of the inner DT ice interface.In this study,we propose an analytical model to describe the feed-out process of the initial roughness of the inner DT ice interface.The perturbation amplitude derived from this model serves as the initial seed for the late-time RTI during the acceleration phase.Our findings confirm the presence of classical-like RTI at the fuel-ablator interface.Numerical simulations conducted using a radiation hydrodynamic code validate the proposed analytical model and demonstrate the existence of a peak mode number in both the feed-out process and the classical-like RTI.It provides an alternative bridge between the current target fabrication limitations and the unexpected implosion performance.展开更多
Mechanical snap-through instability of bi-stable structures may find many practical applications such as state switching and energy transforming.Although there exist diverse bi-stable structures capable of snap-throug...Mechanical snap-through instability of bi-stable structures may find many practical applications such as state switching and energy transforming.Although there exist diverse bi-stable structures capable of snap-through instability,it is still difficult for a structure with high slenderness to undergo the axial snap-through instability with a large stroke.Here,an elastic structure with high slenderness is simply constructed by a finite number of identical,conventional bi-stable units with relatively low slenderness in series connection.For realizing the axial snap-through instability with a large stroke,common scissors mechanisms are further introduced as rigid constraints to guarantee the synchronous snap-through instability of these bi-stable units.The global feature of the large-stroke snap-through instability realized here is robust and even insusceptible to the local out-of-synchronization of individual units.The present design provides a simple and feasible way to achieve the large-stroke snap-through instability of slender structures,which is expected to be particularly useful for state switching and energy transforming in narrow spaces.展开更多
Rotating Instability (RI) is a typical unsteady flow phenomenon in compressors and may cause severe aerodynamic noise and even potential nonsynchronous vibration. Most studies of RI are based on the uniform inflow, ig...Rotating Instability (RI) is a typical unsteady flow phenomenon in compressors and may cause severe aerodynamic noise and even potential nonsynchronous vibration. Most studies of RI are based on the uniform inflow, ignoring the influence of inlet distortions. This study investigates the mechanism of RI in a transonic rotor through full-annulus unsteady simulations, with a particular focus on the effects of boundary layer ingesting distortions. The results show that at the uniform inflow, the RI fluctuations with the broadband hump can be observed over a relatively wide mass flow rate range, and its origin can be attributed to the coupling effect between the tip leakage flow and shear layer instability. At the inlet distortions, the broadband hump only occurs with partial circumferential locations. This kind of flow phenomenon is defined as Partial Rotating Instability (PRI). The PRI only occurs in a narrower mass flow rate range in which the circumferential range of strong shear is sufficiently large and the self-induced unsteady effects are strong enough. Further, this study confirms that the averaged tip leakage flow axial momentum at the onset of RI or PRI is close, so it can be used as the parameter to determine whether RI or PRI occurs.展开更多
A hydrodynamic model is used to study Kelvin-Helmholtz(KH)instability of the interface between two particle-laden inviscid fluids moving with two different uniform mean velocities.Explicit eigen-equation is derived to...A hydrodynamic model is used to study Kelvin-Helmholtz(KH)instability of the interface between two particle-laden inviscid fluids moving with two different uniform mean velocities.Explicit eigen-equation is derived to study the effect of suspended particles on the growth rate of KH instability.For dusty gases with negligible volume fraction of heavy particles and small particle-to-fluid mass ratio,the real and imaginary parts of leading-order asymptotic expression derived by the present model for the growth rate are shown to be identical to the earlier results derived by the classical Saffman model established for dusty gases.Beyond the known results,explicit leading-order asymptotic expressions for the effect of suspended particles on the growth rate are derived for several typical cases of basic interest.It is shown that the suspended particles can decrease or increase the growth rate of KH instability depending on the Stokes numbers of the particles and whether the particles are heavier or lighter than the clean fluid.Compared to the mass density of the clean fluid,our results based on leading-order asymptotic solutions show that heavier particles and lighter particles have opposite effects on the growth rate of KH instability,while the effect of neutrally buoyant particles on the growth rate of KH instability is negligible.展开更多
1.Challenges Thermoacoustic instability in combustors arises from the interaction between sound waves and unsteady heat release,commonly found in systems like gas turbines and aeroengines.This instability leads to und...1.Challenges Thermoacoustic instability in combustors arises from the interaction between sound waves and unsteady heat release,commonly found in systems like gas turbines and aeroengines.This instability leads to undesirable consequences such as structural damage and performance deterioration.The challenge lies in predicting and mitigating these instabilities due to the complex interplay of various physical phenomena like acoustic propagation,turbulent flow,and combustion chemistry,which are summarized in detail in Aimee S.Morgans and Dong Yang's published article.展开更多
Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-...Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-H)CRC is characterized by heightened systemic inflammation,altered cytokine profiles,and unique gut microbiota compositions.Concurrently,MSI-H patients often exhibit poorer nutritional status,as reflected by lower body mass index,decreased serum albumin,and metabolic dysregulation.These immunonutritional alterations influence patient outcomes by affecting prognosis,response to therapy,and overall survival.This editorial summarizes current evidence linking MSI status with inflammatory and nutritional markers,highlighting the clinical implications of integrating nutritional assessment and inflammatory modulation into the maagement of CRC patients.展开更多
The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the...The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the study reveals that MSI-high tumors are associated with significantly lower serum albumin,body mass index,and absolute lymphocyte counts,alongside elevated neutrophil-tolymphocyte ratios compared to microsatellite stable tumors.These findings highlight distinct immunological and nutritional profiles in MSI-high CRC,suggesting potential clinical utility in risk stratification and personalized treat-ment.While the study underscores the importance of MSI status in CRC mana-gement,its single-center design and limited sample size warrant validation through multicenter trials.This article contextualizes these findings within the broader landscape of CRC research,emphasizing the need for integrating bio-markerdriven strategies into clinical practice to optimize outcomes for patients with differing MSI statuses.展开更多
We study the Rayleigh-Taylor instability(RTI)of electrostatic plane wave perturbations in compressible relativistic magnetoplasma fluids with thermal ions under gravity in three different cases of when(ⅰ)electrons ar...We study the Rayleigh-Taylor instability(RTI)of electrostatic plane wave perturbations in compressible relativistic magnetoplasma fluids with thermal ions under gravity in three different cases of when(ⅰ)electrons are in isothermal equilibrium,i.e.,classical or nondegenerate,(ⅱ)electrons are fully degenerate(with Te=0),and(ⅲ)electrons are partially degenerate or have finite temperature degeneracy(with Te≠0).While in the cases of(ⅰ)and(ⅲ),we focus on the regimes where the particle's thermal energy is more or less than the rest mass energy,i.e.,βe≡kBTe/mec2<1or>1,the case(ⅱ)considers from weakly to ultra-relativistic degenerate regimes.A general expression of the growth rate of instability is obtained and analyzed in the three different cases relevant to laboratory and astrophysical plasmas,which generalize and advance the previous theory on RTI.展开更多
To investigate the instability mechanisms of heterogeneous geological structures in goaf area roofs,three-point bending tests(TPBT)and numerical simulations are performed on composite coal-rock(CCR).Acoustic emission(...To investigate the instability mechanisms of heterogeneous geological structures in goaf area roofs,three-point bending tests(TPBT)and numerical simulations are performed on composite coal-rock(CCR).Acoustic emission(AE)monitoring is employed to analyze key parameters,establishing a multiparameter quantitative system for CCR fracture processes.The impact of lithological homogeneity on fracture evolution and energy migration is examined.Results show that CCR exhibits a three-stage mechanical response:weak contact,strong contact,and post-peak stages,each with distinct crack evolution patterns.A positive correlation is found between lithological homogeneity and tensile crack proportion.No significant correlation is observed between AE average frequency(AF)and AE counts across different lithological CCR;however,peak frequency(PF)displays clear lithology-dependent characteristics.The regulatory effect of the rock homogeneity coefficient(φ)on crack deriva tion mechanisms is quantfied,yielding mathematical relationships between fracture strength(f),crack propagation path angle(β),crack fractal dimension(D),andφ.The study highlights how different fracture modes alter energy migration pathways,confirming the coupling effect of grain distribution on mechanical response and crack propagation,and the influence of parameterφon critical energy release zones.These findings offer new insights into CCR failure mechanisms for mining safety.展开更多
Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their asso...Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their association in South Korea remains underexplored.This study investigates LS-associated pathogenic germline variants in MSI-H GC patients using whole-exome sequencing(WES)on normal tissues.Methods:This retrospective study included patients who underwent gastrectomy for GC at Soonchunhyang University Bucheon and Cheonan Hospitals from January 2011 to October 2023.Among 1,537 patients screened for MSI status,127(8.3%)were identified as MSI-H.WES was performed on normal tissues from 123 patients.Pathogenic/likely pathogenic(P/LP)variants in mismatch repair(MMR)genes were identified using in silico models and protein loss assessments in corresponding tumor tissues.Results:Of the 127 MSI-H GC cases,characteristics aligned with typical MSI-H GC.The average age was70.02 years,with 98(77.2%)located in the lower body and 81(63.8%)of the intestinal type.All five MSI markers were positive in 46.5%of cases,whereas four markers were positive in 27.6%.Of the MSI-H GCs,10 LS candidates were identified.Three patients had known P/LP variants[MLH1(c.1758dup),MSH6(c.3261dup),MSH2(c.1241T>C)].Seven patients had variants of unknown significance(VUS)in MMR genes.Six(4.9%)patients were identified as having LS or possible LS,including one patient with the MLH1(c.1153C>T)variant previously classified as VUS but now considered LS-associated.Conclusions:This large-scale screening for LS in MSI-H GC patients using retrospective samples confirmed the lower incidence of LS than those of colorectal or endometrial cancer and GC patients in Western countries,emphasizing the need for clinical consideration in managing MSI-H GC patients.展开更多
This study introduced an innovative numerical approach to examine combustion instability in Solid Rocket Motors(SRMs).The paper commenced with the derivation of a transient model for the solid propellant's condens...This study introduced an innovative numerical approach to examine combustion instability in Solid Rocket Motors(SRMs).The paper commenced with the derivation of a transient model for the solid propellant's condensed phase,followed by its numerical discretization.Subsequently,this model was integrated with gas phase computations of the chamber's internal flow field,encompassing fluid dynamics and combustion processes.The precision of the numerical method was validated by experimental data,and its reliability was confirmed through a grid independence analysis.The study then investigated the motor's stability under various operating conditions,revealing the impact of parameters such as the sensitivity coefficient of the burning rate to temperature and the nozzle throat diameter on the motor's stability.The results confirmed the bistable nature of combustion instability in specific regions.For instance,when the sensitivity coefficients of burning rate to ambient temperature(k_(1))ranged from 1.4 to 1.8,the SRM adopted in this study with a throat diameter of 0.12 m remained stable under small disturbances but triggered instability under large disturbances.Moreover,increasing the value of k_(1)and reducing the throat diameter can exacerbate combustion instability,leading to more pronounced nonlinear characteristics.The numerical method developed in this paper could effectively capture the nonlinear features of the combustion instability occurring in the motor,providing guidance for SRMs design.展开更多
Shallow-buried thick sand strata present considerable local instability risks during diaphragm wall trenching construction.However,this critical issue has not been extensively studied,despite its serious safety conseq...Shallow-buried thick sand strata present considerable local instability risks during diaphragm wall trenching construction.However,this critical issue has not been extensively studied,despite its serious safety consequences.This paper proposes an automatic identification model for shallow-buried thick sand strata,integrating three-dimensional limit equilibrium theory with a genetic algorithm to precisely identify the most potentially dangerous local instability mass and determine its minimum safety factor.The model establishes three undetermined parameters:failure angle,upper boundary,and thickness of the local instability mass.These parameters define the search space for the local instability mass.The effectiveness of this approach was confirmed through a diaphragm wall engineering case near the Rhine River in France,where the predicted instability location closely aligned with field observations.A systematic analysis of the model indicated that the difference in slurry-groundwater levels and the friction angle are the most significant factors affecting local instability in shallow-buried thick sand strata.The model indicated that the location of the most potentially dangerous instability mass changes depending on geological conditions,and larger instability masses do not always relate to lower safety factors.Additionally,exploratory experiments revealed that support pressure losses caused by slurry infiltration significantly influence local instability calculations in sand strata.This points out the importance of considering these support pressure losses in the stability evaluations of high permeable sand strata.The results improve the evaluation of safety and the optimization of design for diaphragm wall construction in shallow-buried thick sand strata.展开更多
This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic ...This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic response mechanism of coal energy evolution is examined, and the energy instability criterion is established. The validity of the instability criterion is explored from the standpoint of damage progression. The results demonstrate that the energy conversion mechanism undergoes a fundamental alternation under impact disturbance. Moreover, the energy release rate as well as the energy dissipation rate undergo comparable changes across distinct levels of impact disturbance. The distinction between the energy release rate and the energy dissipation rate (DRD) increases as coal mass deformation grows. Prior to coal facing instability and failure, the DRD experienced an inflection point followed by a sharp decrease. In conjunction with the discussion on the damage evolution, the physical and mechanical significance of DRD remains clear, which can essentially describe the whole impact loading process. The phenomenon that the inflection point appears and DRD subsequently suddenly decreases can be employed as the energy criterion prior to the failure of instability. Furthermore, this paper provides significant reference for the prediction of dynamic instability of coal under dynamic disturbance.展开更多
文摘High microsatellite instability(MSI-H)colorectal cancer(CRC),caused by deficient mismatch repair,accounts for about 15%of all CRC cases and is more common in right-sided tumors.While early-stage MSI-H CRC has a relatively good prognosis,advanced cases often respond poorly to standard chemotherapy.Immune checkpoint inhibitors,such as pembrolizumab,have shown strong and lasting effects in MSI-H CRC.Pembrolizumab is now approved as a first-line treatment for metastatic MSI-H CRC due to its superior outcomes compared to traditional chemotherapy.CASE SUMMARY A 44-year-old male with MSI-H transverse colon cancer presented with hematochezia,abdominal pain,and significant weight loss.Imaging revealed a bulky tumor with invasion of adjacent structures and multiple liver lesions.A diverting ileostomy was performed followed by 36 cycles of pembrolizumab.The patient achieved a clinical and radiologic complete response.One month after completing the treatment,the patient underwent laparoscopic right hemicolectomy.A spontaneous transection of the colon at the original tumor site was unexpectedly identified.Final pathology confirmed pathological complete response(ypT0N0)with fibrosis.The patient recovered well after surgery,and follow-up showed no evidence of recurrence.CONCLUSION Immune checkpoint inhibitors may cause delayed structural damage to bowel tissue even after apparent complete tumor regression.
基金financially supported by the National Natural Science Foundation of China(Grant No.12072336).
文摘The influence of the squeeze film between the tube and the support structure on flow-induced vibrations is a critical factor in tube bundles subjected to two-phase cross-flow.This aspect can significantly alter the threshold for fluidelastic instability and affect heat transfer efficiency.This paper presents a mathematical model incorporating the squeeze film force between the tube and the support structure.We aim to clarify the mechanisms underlying fluidelastic instability in tube bundle systems exposed to two-phase flow.Using a self-developed computer program,we performed numerical calculations to examine the influence of the squeeze film on the threshold of fluidelastic instability in the tube bundle system.Furthermore,we analyzed how the thickness and length of the squeeze film affect both the underlying mechanisms and the critical velocity of fluidelastic instability.
基金Project supported by the National Natural Science Foundation of China(Nos.12471367 and12361076)the Research Program of Science and Technology at Universities of Inner Mongolia Autonomous Region(Nos.NJZY19186,NJZY22036,and NJZY23003)。
文摘We are intrigued by the issues of shock instability,with a particular emphasis on numerical schemes that address the carbuncle phenomenon by reducing dissipation rather than increasing it.For a specific class of planar flow fields where the transverse direction exhibits vanishing but non-zero velocity components,such as a disturbed onedimensional(1D)steady shock wave,we conduct a formal asymptotic analysis for the Euler system and associated numerical methods.This analysis aims to illustrate the discrepancies among various low-dissipative numerical algorithms.Furthermore,a numerical stability analysis of steady shock is undertaken to identify the key factors underlying shock-stable algorithms.To verify the stability mechanism,a consistent,low-dissipation,and shock-stable HLLC-type Riemann solver is presented.
基金support from the National Natural Science Foundation of China(No.12002386).
文摘Self-excited longitudinal combustion instabilities were investigated in a hypergolic liquid bipropellant combustor, which applied single dual-swirl coaxial injector. Hot-fire tests were conducted for four different injector geometries, while extensive tests on injection conditions were carried out for each injector geometry. The synchronous measurement of the pressure and heat release rate was applied, successfully capturing the process of the pressure and heat release rate enhanced coupling and developing into in-phase oscillation. By calculating Rayleigh index at the head and middle section of the chamber, it is shown that Rayleigh index of the middle section is even higher than that of the head, indicating a long heat release zone. When the combustion instability occurs, the pressure in propellant manifolds also oscillates with the same frequency and lags behind the oscillation in the combustor. Compared to the oscillation in the outer injector manifold, the oscillation in the inner injector manifold shows a higher correlation with that in the chamber in amplitude and phase. Based on numerical simulations of the multiphase cold flow inside the injector and combustion process in the chamber, it is found that injector geometries affect longitudinal combustion instability by changing spray cone angle. The spray with small cone angle is more sensitive to the modulation of longitudinal pressure wave in combustion simulations, which is more likely to excite the longitudinal combustion instability. Meanwhile, the combustion instability may be related to the pulsating coherent structure generated by the spray fluctuation, which is determined by injection conditions. Besides, a positive feedback closed-loop system associated with the active fluctuation and passive oscillation of the spray is believed to excite and sustain the longitudinal combustion instability.
基金support of the National Natural Science Foundation of China(No.52322603)the Science Center for Gas Turbine Project of China(Nos.P2022-B-II-004-001 and P2023-B-II-001-001)+1 种基金the Fundamental Research Funds for the Central Universities,Chinathe Beijing Nova Program of China(Nos.20220484074 and 20230484479).
文摘The utilization of Inlet Guide Vane (IGV) plays a key factor in affecting the instability evolution. Existing literature mainly focuses on the effect of IGV on instability inception that occurs in the rotor region. However, with the emergence of compressor instability starting from the stator region, the mechanism of various instability inceptions that occurs in different blade rows due to the change of IGV angles should be further examined. In this study, experiments were focused on three types of instability inceptions observed previously in a 1.5-stage axial flow compressor. To analyze the conversion of stall evolutions, the compressor rotating speed was set to 17 160 r/min, at which both the blade loading in the stator hub region and rotor tip region were close to the critical value before final compressor stall. Meanwhile, the dynamic test points with high-response were placed to monitor the pressures both at the stator trailing edges and rotor tips. The results indicate that the variation of reaction determines the region where initial instability occurs. Indeed, negative pre-rotation of the inlet guide vane leads to high-reaction, initiating stall disturbance from the rotor region. Positive pre-rotation results in low-reaction, initiating stall disturbance from the stator region. Furthermore, the type of instability evolution is affected by the radial loading distribution under different IGV angles. Specifically, a spike-type inception occurs at the rotor blade tip with a large angle of attack at the rotor inlet (−2°, −4° and −6°). Meanwhile, the critical total pressure ratio at the rotor tip is 1.40 near stall. As the angle of attack decreases, the stator blade loading reaches its critical boundary, with a value of approximately 1.35. At this moment, if the rotor tip maintains high blade loading similar to the stator hub, the partial surge occurs (0° and +2°);otherwise, the hub instability occurs (+4° and +6°).
基金was supported by the National Key Research and Development Program of China(Grant Nos.2024YFA1611200 and 2018YFA0307000)the National Natural Science Foundation of China(Grant Nos.12274154 and 12404182)。
文摘In order to calculate the multipoles in real materials with considerable intersite Coulomb interaction V,we develop a self-consistent program which starts from the frst-principles calculations to solve the tight-binding Hamiltonian including onsite Coulomb repulsion U,V,and spin-orbital couplingλ.The program is applied to Ba_(2)MgReO_(6)to fgure out the mechanism of structural instability and magnetic ordering.A comprehensive quadrupole phase diagram versus U and V withλ=0.28 eV is calculated.Our results demonstrate that the easy-plane anisotropy and the intersite Coulomb repulsion V must be considered to remove the orbital frustration.The increase of V to>20 meV would arrange quadrupole Q_(x^(2)-y^(2))antiparallelly,accompanied by small parallel Q_(3z)^(2)-r^(2),and stabilize Ba_(2)MgReO_(6)into the body-centered tetragonal structure.Such antiparallel Q_(x^(2)-y^(2))provides a new mechanism for the Dzyaloshinskii-Moriya interaction and gives rise to the canted antiferromagnetic(CAF)state along the[110]axis.Moreover,sizable octupoles such as O_(21)^(31),O_(21)^(33),O_(21)^(34)and O_(21)^(36)are discovered for the frst time in the CAF state.Our study not only provides a comprehensive understanding of the experimental results in Ba_(2)MgReO_(6),but also serves as a general and useful tool for the study of multipole physics in 5d compounds.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant Nos.12074399,12204500,and 12004403)the Key Projects of the Intergovernmental International Scientifi and Technological Innovation Cooperation(Grant No.2021YFE0116700)+1 种基金the Shanghai Natural Science Foundation(Grant No.20ZR1464400)the Shanghai Sailing Program(Grant No.22YF1455300)。
文摘The effect of drive laser wavelength on the growth of ablative Rayleigh–Taylor instability(ARTI)in inertial confinemen fusion(ICF)is studied with two-dimensional numerical simulations.The results show that in the plasma acceleration phase,shorter wavelengths lead to more efficien coupling between the laser and the kinetic energy of the implosion fluid Under the condition that the laser energy coupled to the implosion flui is constant,the ARTI growth rate decreases as the laser wavelength moves toward the extreme ultraviolet band,reaching its minimum value near λ=65 nm,and when the laser wavelength continuously moves toward the X-ray band,the ARTI growth rate increases rapidly.It is found that the results deviate from the theoretical ARTI growth rate.As the laser intensity benchmark increases,the position of the minimum ARTI growth rate shifts toward shorter wavelengths.As the initial sinusoidal perturbation wavenumber decreases,the position of the minimum ARTI growth rate shifts toward longer wavelengths.We believe that the conclusions drawn from the present simulations and analysis will help provide a better understanding of the ICF process and improve the theory of ARTI growth.
基金funded by the National Key R&D Program of China(Grant No.2023YFA1608400)the National Natural Science Foundation of China(Grant No.12302281).
文摘Hydrodynamic instability growth at the deuterium-tritium(DT)fuel-ablator interface plays a critical role in determining the performance of inertial confinement fusion implosions.During the late stages of implosion,insufficient doping of the ablator material can result in highenergy X-ray preheat,which may trigger the development of a classical-like Rayleigh-Taylor instability(RTI)at the fuel-ablator interface.In implosion experiments at the Shenguang 100 kJ-level laser facility,the primary source of perturbation is the roughness of the inner DT ice interface.In this study,we propose an analytical model to describe the feed-out process of the initial roughness of the inner DT ice interface.The perturbation amplitude derived from this model serves as the initial seed for the late-time RTI during the acceleration phase.Our findings confirm the presence of classical-like RTI at the fuel-ablator interface.Numerical simulations conducted using a radiation hydrodynamic code validate the proposed analytical model and demonstrate the existence of a peak mode number in both the feed-out process and the classical-like RTI.It provides an alternative bridge between the current target fabrication limitations and the unexpected implosion performance.
基金supported by the National Natural Science Foundation of China(Grant Nos.11972027,12472093,and 11772272)the New Interdisciplinary Cultivation Fund of Southwest Jiaotong University(Grant No.2682022JX001)+1 种基金the Frontier Science and Technology Cultivation Project of Southwest Jiaotong University(Grant No.2682022KJ048)the Laboratory of Flexible Electronics Technology at Tsinghua University.
文摘Mechanical snap-through instability of bi-stable structures may find many practical applications such as state switching and energy transforming.Although there exist diverse bi-stable structures capable of snap-through instability,it is still difficult for a structure with high slenderness to undergo the axial snap-through instability with a large stroke.Here,an elastic structure with high slenderness is simply constructed by a finite number of identical,conventional bi-stable units with relatively low slenderness in series connection.For realizing the axial snap-through instability with a large stroke,common scissors mechanisms are further introduced as rigid constraints to guarantee the synchronous snap-through instability of these bi-stable units.The global feature of the large-stroke snap-through instability realized here is robust and even insusceptible to the local out-of-synchronization of individual units.The present design provides a simple and feasible way to achieve the large-stroke snap-through instability of slender structures,which is expected to be particularly useful for state switching and energy transforming in narrow spaces.
基金supports of the National Natural Science Foundation of China(Nos.52076129,92360308,52376027)the Shanghai Municipal Education Commission of China(No.2023-02-4)+1 种基金the Fundamental Research Funds for the Central Universities of Chinathe United Innovation Center(UIC)of Aerothermal Technologies for Turbomachinery of China.
文摘Rotating Instability (RI) is a typical unsteady flow phenomenon in compressors and may cause severe aerodynamic noise and even potential nonsynchronous vibration. Most studies of RI are based on the uniform inflow, ignoring the influence of inlet distortions. This study investigates the mechanism of RI in a transonic rotor through full-annulus unsteady simulations, with a particular focus on the effects of boundary layer ingesting distortions. The results show that at the uniform inflow, the RI fluctuations with the broadband hump can be observed over a relatively wide mass flow rate range, and its origin can be attributed to the coupling effect between the tip leakage flow and shear layer instability. At the inlet distortions, the broadband hump only occurs with partial circumferential locations. This kind of flow phenomenon is defined as Partial Rotating Instability (PRI). The PRI only occurs in a narrower mass flow rate range in which the circumferential range of strong shear is sufficiently large and the self-induced unsteady effects are strong enough. Further, this study confirms that the averaged tip leakage flow axial momentum at the onset of RI or PRI is close, so it can be used as the parameter to determine whether RI or PRI occurs.
文摘A hydrodynamic model is used to study Kelvin-Helmholtz(KH)instability of the interface between two particle-laden inviscid fluids moving with two different uniform mean velocities.Explicit eigen-equation is derived to study the effect of suspended particles on the growth rate of KH instability.For dusty gases with negligible volume fraction of heavy particles and small particle-to-fluid mass ratio,the real and imaginary parts of leading-order asymptotic expression derived by the present model for the growth rate are shown to be identical to the earlier results derived by the classical Saffman model established for dusty gases.Beyond the known results,explicit leading-order asymptotic expressions for the effect of suspended particles on the growth rate are derived for several typical cases of basic interest.It is shown that the suspended particles can decrease or increase the growth rate of KH instability depending on the Stokes numbers of the particles and whether the particles are heavier or lighter than the clean fluid.Compared to the mass density of the clean fluid,our results based on leading-order asymptotic solutions show that heavier particles and lighter particles have opposite effects on the growth rate of KH instability,while the effect of neutrally buoyant particles on the growth rate of KH instability is negligible.
文摘1.Challenges Thermoacoustic instability in combustors arises from the interaction between sound waves and unsteady heat release,commonly found in systems like gas turbines and aeroengines.This instability leads to undesirable consequences such as structural damage and performance deterioration.The challenge lies in predicting and mitigating these instabilities due to the complex interplay of various physical phenomena like acoustic propagation,turbulent flow,and combustion chemistry,which are summarized in detail in Aimee S.Morgans and Dong Yang's published article.
文摘Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-H)CRC is characterized by heightened systemic inflammation,altered cytokine profiles,and unique gut microbiota compositions.Concurrently,MSI-H patients often exhibit poorer nutritional status,as reflected by lower body mass index,decreased serum albumin,and metabolic dysregulation.These immunonutritional alterations influence patient outcomes by affecting prognosis,response to therapy,and overall survival.This editorial summarizes current evidence linking MSI status with inflammatory and nutritional markers,highlighting the clinical implications of integrating nutritional assessment and inflammatory modulation into the maagement of CRC patients.
文摘The retrospective cohort study by Zuo et al investigates the interplay between microsatellite instability(MSI)status,nutritional indicators,and inflammatory profiles in colorectal cancer(CRC).Analyzing 56 patients,the study reveals that MSI-high tumors are associated with significantly lower serum albumin,body mass index,and absolute lymphocyte counts,alongside elevated neutrophil-tolymphocyte ratios compared to microsatellite stable tumors.These findings highlight distinct immunological and nutritional profiles in MSI-high CRC,suggesting potential clinical utility in risk stratification and personalized treat-ment.While the study underscores the importance of MSI status in CRC mana-gement,its single-center design and limited sample size warrant validation through multicenter trials.This article contextualizes these findings within the broader landscape of CRC research,emphasizing the need for integrating bio-markerdriven strategies into clinical practice to optimize outcomes for patients with differing MSI statuses.
基金support from the University Grants Commission(UGC),Government of India,for a Senior Research Fellowship(SRF)with Ref.No.1161/(CSIR-UGC NET DEC.2018)and 16-6(DEC.2018)/2019(NET/CSIR)。
文摘We study the Rayleigh-Taylor instability(RTI)of electrostatic plane wave perturbations in compressible relativistic magnetoplasma fluids with thermal ions under gravity in three different cases of when(ⅰ)electrons are in isothermal equilibrium,i.e.,classical or nondegenerate,(ⅱ)electrons are fully degenerate(with Te=0),and(ⅲ)electrons are partially degenerate or have finite temperature degeneracy(with Te≠0).While in the cases of(ⅰ)and(ⅲ),we focus on the regimes where the particle's thermal energy is more or less than the rest mass energy,i.e.,βe≡kBTe/mec2<1or>1,the case(ⅱ)considers from weakly to ultra-relativistic degenerate regimes.A general expression of the growth rate of instability is obtained and analyzed in the three different cases relevant to laboratory and astrophysical plasmas,which generalize and advance the previous theory on RTI.
基金support from the National Key Research and Development Plan Project(No.2022YFC3004700)the National Natural Science Foundation of China(No.52374241)+1 种基金Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX24_2924)Graduate Innovation Program of China University of Mining and Technology(No.2024WLKXJ151).
文摘To investigate the instability mechanisms of heterogeneous geological structures in goaf area roofs,three-point bending tests(TPBT)and numerical simulations are performed on composite coal-rock(CCR).Acoustic emission(AE)monitoring is employed to analyze key parameters,establishing a multiparameter quantitative system for CCR fracture processes.The impact of lithological homogeneity on fracture evolution and energy migration is examined.Results show that CCR exhibits a three-stage mechanical response:weak contact,strong contact,and post-peak stages,each with distinct crack evolution patterns.A positive correlation is found between lithological homogeneity and tensile crack proportion.No significant correlation is observed between AE average frequency(AF)and AE counts across different lithological CCR;however,peak frequency(PF)displays clear lithology-dependent characteristics.The regulatory effect of the rock homogeneity coefficient(φ)on crack deriva tion mechanisms is quantfied,yielding mathematical relationships between fracture strength(f),crack propagation path angle(β),crack fractal dimension(D),andφ.The study highlights how different fracture modes alter energy migration pathways,confirming the coupling effect of grain distribution on mechanical response and crack propagation,and the influence of parameterφon critical energy release zones.These findings offer new insights into CCR failure mechanisms for mining safety.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2022R1A2C2092005)the Soonchunhyang University Research Fund。
文摘Objective:Lynch syndrome(LS)increases the risk of various cancers,including colorectal cancer,endometrial cancer and gastric cancer(GC).The incidence of LS among microsatellite instability-high(MSI-H)GC and their association in South Korea remains underexplored.This study investigates LS-associated pathogenic germline variants in MSI-H GC patients using whole-exome sequencing(WES)on normal tissues.Methods:This retrospective study included patients who underwent gastrectomy for GC at Soonchunhyang University Bucheon and Cheonan Hospitals from January 2011 to October 2023.Among 1,537 patients screened for MSI status,127(8.3%)were identified as MSI-H.WES was performed on normal tissues from 123 patients.Pathogenic/likely pathogenic(P/LP)variants in mismatch repair(MMR)genes were identified using in silico models and protein loss assessments in corresponding tumor tissues.Results:Of the 127 MSI-H GC cases,characteristics aligned with typical MSI-H GC.The average age was70.02 years,with 98(77.2%)located in the lower body and 81(63.8%)of the intestinal type.All five MSI markers were positive in 46.5%of cases,whereas four markers were positive in 27.6%.Of the MSI-H GCs,10 LS candidates were identified.Three patients had known P/LP variants[MLH1(c.1758dup),MSH6(c.3261dup),MSH2(c.1241T>C)].Seven patients had variants of unknown significance(VUS)in MMR genes.Six(4.9%)patients were identified as having LS or possible LS,including one patient with the MLH1(c.1153C>T)variant previously classified as VUS but now considered LS-associated.Conclusions:This large-scale screening for LS in MSI-H GC patients using retrospective samples confirmed the lower incidence of LS than those of colorectal or endometrial cancer and GC patients in Western countries,emphasizing the need for clinical consideration in managing MSI-H GC patients.
基金supported by the National Natural Science Foundation of China(No.U2241250)。
文摘This study introduced an innovative numerical approach to examine combustion instability in Solid Rocket Motors(SRMs).The paper commenced with the derivation of a transient model for the solid propellant's condensed phase,followed by its numerical discretization.Subsequently,this model was integrated with gas phase computations of the chamber's internal flow field,encompassing fluid dynamics and combustion processes.The precision of the numerical method was validated by experimental data,and its reliability was confirmed through a grid independence analysis.The study then investigated the motor's stability under various operating conditions,revealing the impact of parameters such as the sensitivity coefficient of the burning rate to temperature and the nozzle throat diameter on the motor's stability.The results confirmed the bistable nature of combustion instability in specific regions.For instance,when the sensitivity coefficients of burning rate to ambient temperature(k_(1))ranged from 1.4 to 1.8,the SRM adopted in this study with a throat diameter of 0.12 m remained stable under small disturbances but triggered instability under large disturbances.Moreover,increasing the value of k_(1)and reducing the throat diameter can exacerbate combustion instability,leading to more pronounced nonlinear characteristics.The numerical method developed in this paper could effectively capture the nonlinear features of the combustion instability occurring in the motor,providing guidance for SRMs design.
基金supported by the Fundamental Research Funds for the Central Universities(No.02302350113).
文摘Shallow-buried thick sand strata present considerable local instability risks during diaphragm wall trenching construction.However,this critical issue has not been extensively studied,despite its serious safety consequences.This paper proposes an automatic identification model for shallow-buried thick sand strata,integrating three-dimensional limit equilibrium theory with a genetic algorithm to precisely identify the most potentially dangerous local instability mass and determine its minimum safety factor.The model establishes three undetermined parameters:failure angle,upper boundary,and thickness of the local instability mass.These parameters define the search space for the local instability mass.The effectiveness of this approach was confirmed through a diaphragm wall engineering case near the Rhine River in France,where the predicted instability location closely aligned with field observations.A systematic analysis of the model indicated that the difference in slurry-groundwater levels and the friction angle are the most significant factors affecting local instability in shallow-buried thick sand strata.The model indicated that the location of the most potentially dangerous instability mass changes depending on geological conditions,and larger instability masses do not always relate to lower safety factors.Additionally,exploratory experiments revealed that support pressure losses caused by slurry infiltration significantly influence local instability calculations in sand strata.This points out the importance of considering these support pressure losses in the stability evaluations of high permeable sand strata.The results improve the evaluation of safety and the optimization of design for diaphragm wall construction in shallow-buried thick sand strata.
基金Projects(51934007,12072363,52004268) supported by the National Natural Science Foundation of ChinaProject(22KJD440002) supported by the Natural Science Fund for Colleges and Universities in Jiangsu Province,China。
文摘This study investigates the instability characteristics of dynamic disasters resulting from disruption caused by extracting resources underground. Utilizing the split Hopkinson pressure bar (SHPB) system, the dynamic response mechanism of coal energy evolution is examined, and the energy instability criterion is established. The validity of the instability criterion is explored from the standpoint of damage progression. The results demonstrate that the energy conversion mechanism undergoes a fundamental alternation under impact disturbance. Moreover, the energy release rate as well as the energy dissipation rate undergo comparable changes across distinct levels of impact disturbance. The distinction between the energy release rate and the energy dissipation rate (DRD) increases as coal mass deformation grows. Prior to coal facing instability and failure, the DRD experienced an inflection point followed by a sharp decrease. In conjunction with the discussion on the damage evolution, the physical and mechanical significance of DRD remains clear, which can essentially describe the whole impact loading process. The phenomenon that the inflection point appears and DRD subsequently suddenly decreases can be employed as the energy criterion prior to the failure of instability. Furthermore, this paper provides significant reference for the prediction of dynamic instability of coal under dynamic disturbance.
