Analyzed the support instable mode of sliding,tripping,and so on,and believed the key point of the support stability control of fully mechanized coal caving face with steep coal seams was to maintain that the seam tru...Analyzed the support instable mode of sliding,tripping,and so on,and believed the key point of the support stability control of fully mechanized coal caving face with steep coal seams was to maintain that the seam true angle was less than the hydraulic support instability critical angle.Through the layout of oblique face,the improvement of support setting load,the control of mining height and nonskid platform,the group support system of end face,the advance optimization of conveyor and support,and the other control tech- nical measures,the true angle of the seam is reduced and the instable critical angle of the support is increased,the hydraulic support stability of fully mechanized coal caving face with steep coal seams is effectively controlled.展开更多
The Kuroshio frontal instable processes （KFIP） in the East China Sea （ECS） not only have a great impact on the hydrologic characteristics,the pollutants drift,the distribution of seafloor sediment and the ships na...The Kuroshio frontal instable processes （KFIP） in the East China Sea （ECS） not only have a great impact on the hydrologic characteristics,the pollutants drift,the distribution of seafloor sediment and the ships navigation of the ECS,but also are closely related to the climate changes of the coastal areas of the ECS.However the frequency and area of occurrence of the KFIP have not been studied fully and detailedly.Because of its high spatial and temporal resolution,MODIS data is a kind of very good data source for surveying and researching the KFIP in the ECS.The aim of this study is to detect the KFIP in the ECS by using MODIS data,and to study the frequency and region of occurrence of the KFIP in the ECS.The selection has coverage of level 2 data of MODIS SST and Kd490 ranging from July 1,2002 to June 30,2009 of the ECS when there was no cloud impact or little.By using of the data,the minimum standard of the Kuroshio temperature fronts and the diffuse attenuation coefficient （Kd490） fronts of the ECS are given.Based on these standards and the curvature distinguish methods,the standard of curvature distinguish for the KFIP in the ECS are put forward.By making use of this standard,we study a total of 2073 satellite-derived images,and discover that as long as there is no cloud impact from January to May and October to December,the KFIP in the ECS are surely found in MODIS satellite images.From June to September,the frequency of occurrence can also reach to 82.9% at least.Moreover,it is obtained that there are three source regions of these instability processes,namely,（26°N,121.5°E） nearby,（27°N,125°E） nearby and （30°N,128°E） nearby.The differences of the characteristics of these instability processes which are generated in different regions are analyzed in the present study.展开更多
In this paper, we aim to control an instable chaotic oscillation in power system that is considered to be small system by using a linear state feedback controller. First we will analyze the stability of the mentioned ...In this paper, we aim to control an instable chaotic oscillation in power system that is considered to be small system by using a linear state feedback controller. First we will analyze the stability of the mentioned power system by means of modern nonlinear theory (Bifurcation and Chaos). Our model is based on a three bus power system that consists of multi generators containing both dynamic and static loads. They are considered to be in the form of an induction motor in parallel with a capacitor, as well as a combination of constant power along with load impedance, PQ. We consider the load reactive power as the control parameter. At this stage, after changing the control parameter, the study showed that the system is experiencing a subcritical Hopf bifurcation point. This leads to a chaos within the system period doubling path. We then discuss the system controllability and present that the all chaotic oscillations fade away through the linear controller that we impose on the system.展开更多
The instable combustion or oscillation combustion which occurs in three high capacity solid rocket motors using high energy composite propellant with finocyl grain is studied. The reasons of the acoustic combustion in...The instable combustion or oscillation combustion which occurs in three high capacity solid rocket motors using high energy composite propellant with finocyl grain is studied. The reasons of the acoustic combustion instability are also discussed. Three engineering methods that can eliminate combustion instability are proposed and discussed. The study shows that the combustion instability mainly depends on the propellant grain shape and nozzle structure. Some measures to reduce the acoustic energy and mass generation rate of combustion gas can be adopted. The test results indicate that the modified rocket motors can significantly eliminate the instable combustion and improve the motor internal ballistic performance.展开更多
AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a prognostic indicator by assessing MSI status of patients with double primary gastric and colorectal cancer (DPGCC).METHODS: Sixteen patients ...AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a prognostic indicator by assessing MSI status of patients with double primary gastric and colorectal cancer (DPGCC).METHODS: Sixteen patients were studied, all of whom exhibited sporadic DPGCC, and had no family history of hereditary non-polyposis colorectal cancer, according to the Amsterdam criteria. A total of 32 cancers from 16DPGCC patients, and 216 single primary CRC, were assessed for MSI in 5 microsatellite loci, BAT25, BAT26,D2S123, D5S346, and D17S250.RESULTS: MSI was observed in 6 (37.5%) of 16 GC and 4 (25.0%) of 16 CRC. Thirty tumors (13.9%) out of 216single primary CRC and one tumor (16.7%) out of 6 double primary CRC were found to be microsatellite unstable. Of the 6 GC with MSI in DPGCC, 5 (31.3%) were MSI-high and one (6.3%) was MSI-low. In 5 of 16 DPGCC patients,the cancer recurred in or adjacent to the anastomosis or metastasized to the kidney or lung. The MSI-high DPGCC cases were associated with a younger age of onset (47.5 years vs 62.5 years), higher frequency of lymph node metastasis (100% vs 25%), and advanced Dukes stage (C, 100% vs 41.7%), as well as a higher frequency of recurrence or metastasis (100% vs 8.3%). Only recurrence or metastasis showed statistical significance by Fisher's exact test.CONCLUSION: Our data suggest that MSI may play an important role in the development of DPGCC, and that it may be used clinically as a molecular predictive marker for recurrence or late metastasis of DPGCC.展开更多
Plasmas,the most common state of matter in the observable universe,are subject to instabilities of various types:hydrodynamic,magnetohydrodynamic,and electromagnetic.Our limited success in understanding these is due t...Plasmas,the most common state of matter in the observable universe,are subject to instabilities of various types:hydrodynamic,magnetohydrodynamic,and electromagnetic.Our limited success in understanding these is due to the lack of direct experimental information on their origins and evolution.Here,we present direct spatially resolved measurements of the femtosecond evolution of the electromagnetic beam-driven instability that arises from the interaction of forward and return currents in an ultrahigh-intensity laser-produced plasma.We track its evolution from the initial linear stage to the later nonlinear stage by measuring the spatiotemporal evolution of the giant(megagauss)magnetic field created in the interaction process.Our experimental findings and numerical simulations are the first to indicate the observed instability triggered by the emission of electromagnetic radiation,like those known in the context of gravitational interaction,where the emission of gravitational radiation drives specific negative-energy modes in rotating black holes or neutron stars.展开更多
The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase ...The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase of ICF implosion,the growth of ARTI can be suppressed by using a short-wavelength spatially modulated laser.The ARTI growth rate decreases as the wavelength of the spatially modulated laser decreases,and ARTI is completely suppressed after a certain wavelength has been reached.A spatially uniform laser is introduced to keep the state of motion of the implosion fluid consistent,and it is found that the proportion of the spatially modulated laser required for complete suppression of ARTI decreases as the wavelength continues to decrease.We also optimize the spatial intensity distribution of the spatially modulated laser.In addition,as the duration of the spatially modulated laser decreases,the proportion required for completely suppressing ARTI increases,but the required energy decreases.When the perturbation wavenumber decreases,the wavelength of the spatially modulated laser required for complete suppression of ARTI becomes longer.In the case of multimode perturbation,ARTI can also be significantly suppressed by a spatially modulated laser,and the perturbation amplitude can be reduced to less than 10% of that without a spatially modulated laser.We believe that the conclusions drawn from our simulations can provide the basis for new approaches to control ARTI in ICF.展开更多
Reaction-diffusion systems are widely used to describe pattern formation,and various control strategies have been applied to reaction-diffusion systems to achieve control objectives such as boundary control,output fee...Reaction-diffusion systems are widely used to describe pattern formation,and various control strategies have been applied to reaction-diffusion systems to achieve control objectives such as boundary control,output feedback stabilization,and synchronization.However,controlling pattern dynamics in reaction-diffusion systems with fractional-order diffusion remains an unresolved problem.This paper presents a proportional-derivative(PD)control strategy for the Schnakenberg system with fractional-order diffusion and cross-diffusion.Theoretical analysis explores the amplitude equation near the Turing bifurcation threshold,determining the selection and stability of pattern formations.Numerical simulations demonstrate that the PD controller accomplishes the modification of pattern structures and suppression of Turing instability by adjusting only two control parameters.Additionally,it is found that for smaller fractional diffusion order,the region can accommodate more hexagonal and stripe patterns in space.This work contributes to the control of complex pattern dynamics and offers a new approach to enhancing stability in fractional reaction-diffusion systems.展开更多
Based on the conventional observation data,daily reanalysis data from NCAR/NCEP,and TBB data derived from FY-2G infrared cloud images in April 2018,a heavy snowfall weather process in central Inner Mongolia from April...Based on the conventional observation data,daily reanalysis data from NCAR/NCEP,and TBB data derived from FY-2G infrared cloud images in April 2018,a heavy snowfall weather process in central Inner Mongolia from April 4 to 6 in 2018 was analyzed.The results show that the low trough at 500 hPa,the southerly wind jet stream at 700 hPa,and the inverted trough on the ground were the main influencing systems causing this blizzard.The transportation of warm and humid air by the southerly wind jet stream at 700 hPa and intense water vapor convergence provided sufficient water vapor conditions for the blizzard,and the moist layer in the blizzard area was deep.The low-level MPV in the blizzard area was<0,and the atmosphere was in a conditional symmetric instability state.The coupling of the upper and lower-level jets induced strong ascending motion.With the invasion of cold air,a low-level cold pad was formed,so that the warm and humid air tilted upward.The secondary circulation updraft triggered by the wet Q vector system released the conditional symmetric instability energy,so that the sloping motion was more intense,and the heavy snowfall appeared.Meanwhile,there was a good correspondence relationship between the blizzard area and the large-value area of low-level wet Q vector divergence.The mesoscale cloud clusters continuously generating,merging,and moving eastward in Hetao area were the direct cause of this blizzard,and the TBB of the cloud clusters was≤-56℃.The blizzard happened in the the edge gradient and large-value area of TBB.展开更多
The Reynolds-averaged Navier-Stokes(RANS)technique enables critical engineering predictions and is widely adopted.However,since this iterative computation relies on the fixed-point iteration,it may converge to unexpec...The Reynolds-averaged Navier-Stokes(RANS)technique enables critical engineering predictions and is widely adopted.However,since this iterative computation relies on the fixed-point iteration,it may converge to unexpected non-physical phase points in practice.We conduct an analysis on the phase-space characteristics and the fixed-point theory underlying the k-ε turbulence model,and employ the classical Kolmogorov flow as a framework,leveraging its direct numerical simulation(DNS)data to construct a one-dimensional(1D)system under periodic/fixed boundary conditions.The RANS results demonstrate that under periodic boundary conditions,the k-ε model exhibits only a unique trivial fixed point,with asymptotes capturing the phase portraits.The stability of this trivial fixed point is determined by a mathematically derived stability phase diagram,indicating the fact that the k-ε model will never converge to correct values under periodic conditions.In contrast,under fixed boundary conditions,the model can yield a stable non-trivial fixed point.The evolutionary mechanisms and their relationship with boundary condition settings systematically explain the inherent limitations of the k-ε model,i.e.,its deficiency in computing the flow field under periodic boundary conditions and sensitivity to boundary-value specifications under fixed boundary conditions.These conclusions are finally validated with the open-source code OpenFOAM.展开更多
Crossflow instability will be present when the vehicle has an angle of attack in hypersonic flow,and it might play a dominant role in hypersonic boundary layer transition.By far the mechanism of crossflow instability-...Crossflow instability will be present when the vehicle has an angle of attack in hypersonic flow,and it might play a dominant role in hypersonic boundary layer transition.By far the mechanism of crossflow instability-induced hypersonic boundary layer transition is still out of understanding,although the large effort has been devoted.Upon this work,the overall roughness effect on instabilities in hypersonic flow was researched experimentally.Surface flush-mounted pressure sensors and infrared camera were employed to investigate the instability waves when different rough surfaces were deployed.The results reveal that the moderate surface roughness level on cone model can suppress the growth of crossflow instabilities at certain azimuthal angles in hypersonic flow.展开更多
The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programmi...The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.展开更多
Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
Roof pre-fracture poses a considerable risk during the re-mining of residual coal above abandoned roadways,threatening the safety of the mining faces.This study employs a Winkler foundation beam model for mechanical a...Roof pre-fracture poses a considerable risk during the re-mining of residual coal above abandoned roadways,threatening the safety of the mining faces.This study employs a Winkler foundation beam model for mechanical analysis of roof structures and adopts a multivariate nonlinear analysis approach to explore the synergistic load-bearing effects within the'coal pillar-support-backfill body'system during the fill and re-mining processes above these roadways.The findings demonstrate that backfill mining significantly reduces stress concentrations in coal pillars and reduces excessive bending moments in roofs near abandoned roadways.The roof deflection equation incorporates three critical factors affecting stability during backfill mining:the width of the coal pillar(L_(3)),the working resistance of the support(q_(z)),and the elastic foundation coefficient of the backfill material(kcÞ.Under single-factor conditions,the impact sequence on roof stability in the coal pillar zone is·k_(c)>L_(3)>q_(z).Further,multivariate nonlinear analysis reveals the interactions within the'coal-support-backfill'structure,indicating that in terms of roof control,the interaction terms are ordered as L_(3)·k_(c)>q_(z)·k_(c)>L_(3)q_(z).Therefore,priority should be given to adjusting the coal pillar width and backfill strength,followed by modifications to the support resistance and backfill strength during the recovery of abandoned roadways.An improved understanding of these interactions will help optimize strategies for the recovery of residual coal through abandoned roadways,thereby enhancing the stability and safety of mining operations under complex geological conditions.展开更多
The deformation and failure of coal walls in front of a working face cause significant difficulties during mining operations.This study reveals the nonuniform distribution of bearing pressure in front of coal walls ba...The deformation and failure of coal walls in front of a working face cause significant difficulties during mining operations.This study reveals the nonuniform distribution of bearing pressure in front of coal walls based on in situ monitoring data and numerical simulation.Therefore,an eccentric compression mechanical model was established to study the deformation and failure characteristics of a coal wall.The slenderness ratio of the compression bar is introduced to define coal walls.The results showed that instability failure occurs when λ>λ_(c) and material failure occurs when λ≤λ_(c).The instability failure-type coal wall spalling was related to the mining height,eccentricity of roof pressure,the horizontal force,and the reaction moment of the floor.The material failure-type coal wall spalling was related to the cohesion,the internal friction angle of the coal,the upper pressure,and the horizontal force of coal walls.Unstable and destructive coal wall peeling usually occurs at a height of 0.5–0.6 times the mining height,while material damage to coal wall peeling is determined to occur within the range of 0.4-0.6 times the mining depth.The findings contribute to the understanding of the deformation and failure of coal walls.展开更多
Snap-through instability-based mechanical metamaterials(SIMMs)with bistability,multistability,negative stiffness,or excellent energy absorption and dissipation performance play an important role in various advanced fu...Snap-through instability-based mechanical metamaterials(SIMMs)with bistability,multistability,negative stiffness,or excellent energy absorption and dissipation performance play an important role in various advanced functional applications.They can serve as energy absorbers,energy dampers,or mechanical memory and logic computing devices,while also providing amplified force output and faster response time in flexible robots,or implementing sensing functions combined with piezoelectric or triboelectric electricity.However,thus far,research on SIMMs that have non-fixed boundary constraints,proactive responsiveness,multi-physical field cross-coupling,and deep information processing capabilities is still facing significant challenges,potentially hindering the development and cross-field comprehensive applications of truly intelligent SIMMs.Our objective is to furnish a concise categorization of SIMMs and offer direction for innovative design and functional implementations.We have emphasized that the non-fixed boundary constraint will expand the design possibilities,while the use of stimulus-responsive materials and 4D printing technology will create novel opportunities for the design of SIMMs.These advancements are expected to achieve innovative mechanical properties and functions.展开更多
GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening o...GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening of US unipolar dominance,requires joint efforts by major international actors and the wider international community to establish a functional international order for the twenty-first century.展开更多
DIS3 is the main catalytic subunit of the nuclear RNA exosome,a complex playing a crucial role in RNA processing and the degradation of various noncoding RNA substrates.In mice,DIS3 is essential for genomic rearrangem...DIS3 is the main catalytic subunit of the nuclear RNA exosome,a complex playing a crucial role in RNA processing and the degradation of various noncoding RNA substrates.In mice,DIS3 is essential for genomic rearrangements during B cell development,but its role in terminal plasma cell(PC)differentiation has not been explored.Although DIS3 gene alterations are frequent in multiple myeloma(MM),a PC malignancy,their molecular impact remains poorly understood.In this study,we developed an antisense oligonucleotide strategy to knock down DIS3 expression in a well-characterized model of human PC differentiation.Reducing DIS3 expression systematically led to decreased B cell proliferation and impaired PC differentiation with lower levels of switched immunoglobulin secretion.Transcriptome analyses confirmed alterations in the proliferation and differentiation programs,alongside an accumulation of noncoding RNAs.Notably,centromere-associated noncoding RNAs were highly sensitive to DIS3 activity,and their accumulation in DIS3-deficient cells,either as transcripts or DNA-associated RNAs,correlated with the mislocalization of the centromere-specific histone variant CENP-A.We finally observed reduced physiological DNA recombination and somatic hypermutation but increased genomic instability in DIS3-deficient cells,in agreement with the higher levels of IGH translocations observed in our large cohort of DIS3-mutant MM patients.Together,these results underscore the essential role of DIS3 in regulating B cell proliferation,DNA recombination,and physiological or malignant PC differentiation in humans.展开更多
The rapid cycling synchrotron(RCS)at the China spallation neutron source operates as a high-intensity proton accelerator.The coupled bunch instability was observed during RCS beam commissioning,which significantly lim...The rapid cycling synchrotron(RCS)at the China spallation neutron source operates as a high-intensity proton accelerator.The coupled bunch instability was observed during RCS beam commissioning,which significantly limited the beam power.To investigate the dynamics of instability under an increased beam power,a pulsed octupole magnet with a gradient of 900 T/m^(3) was developed.The magnet system integrated an octupole magnet with a pulsed power supply.The field was carefully measured to examine the performance before its installation into the tunnel.After the installation of the magnets,beam measurements were performed to confirm the effectiveness of the instability mitigation on an actual proton beam.The measurement results show that the instability can be suppressed using the pulsed octupole magnet,particularly at the highenergy stage in an acceleration cycle,meeting the requirements for stable operation of the accelerator.Additionally,when the instability is completely suppressed through chromaticity optimization,octupole magnets can significantly enhance the RCS transmission efficiency,which is crucial for controlling beam loss.The pulsed octupole magnet offers significant progress in beam stability in the RCS,providing valuable experience for further beam power enhancement.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
基金the National Natrual Science Foundation of China(50504014)
文摘Analyzed the support instable mode of sliding,tripping,and so on,and believed the key point of the support stability control of fully mechanized coal caving face with steep coal seams was to maintain that the seam true angle was less than the hydraulic support instability critical angle.Through the layout of oblique face,the improvement of support setting load,the control of mining height and nonskid platform,the group support system of end face,the advance optimization of conveyor and support,and the other control tech- nical measures,the true angle of the seam is reduced and the instable critical angle of the support is increased,the hydraulic support stability of fully mechanized coal caving face with steep coal seams is effectively controlled.
基金the special funds for marine commonweal research under contract No.200705027variability of the subtropical gyre in North Pacific and its impacts on dynamic environment of China marginal seas under contract No.2007CB411800defense industrial technology development program and the special funds for basic scientific research project of the First Institute of Oceanography,SOA under contract No.2010G12
文摘The Kuroshio frontal instable processes （KFIP） in the East China Sea （ECS） not only have a great impact on the hydrologic characteristics,the pollutants drift,the distribution of seafloor sediment and the ships navigation of the ECS,but also are closely related to the climate changes of the coastal areas of the ECS.However the frequency and area of occurrence of the KFIP have not been studied fully and detailedly.Because of its high spatial and temporal resolution,MODIS data is a kind of very good data source for surveying and researching the KFIP in the ECS.The aim of this study is to detect the KFIP in the ECS by using MODIS data,and to study the frequency and region of occurrence of the KFIP in the ECS.The selection has coverage of level 2 data of MODIS SST and Kd490 ranging from July 1,2002 to June 30,2009 of the ECS when there was no cloud impact or little.By using of the data,the minimum standard of the Kuroshio temperature fronts and the diffuse attenuation coefficient （Kd490） fronts of the ECS are given.Based on these standards and the curvature distinguish methods,the standard of curvature distinguish for the KFIP in the ECS are put forward.By making use of this standard,we study a total of 2073 satellite-derived images,and discover that as long as there is no cloud impact from January to May and October to December,the KFIP in the ECS are surely found in MODIS satellite images.From June to September,the frequency of occurrence can also reach to 82.9% at least.Moreover,it is obtained that there are three source regions of these instability processes,namely,（26°N,121.5°E） nearby,（27°N,125°E） nearby and （30°N,128°E） nearby.The differences of the characteristics of these instability processes which are generated in different regions are analyzed in the present study.
文摘In this paper, we aim to control an instable chaotic oscillation in power system that is considered to be small system by using a linear state feedback controller. First we will analyze the stability of the mentioned power system by means of modern nonlinear theory (Bifurcation and Chaos). Our model is based on a three bus power system that consists of multi generators containing both dynamic and static loads. They are considered to be in the form of an induction motor in parallel with a capacitor, as well as a combination of constant power along with load impedance, PQ. We consider the load reactive power as the control parameter. At this stage, after changing the control parameter, the study showed that the system is experiencing a subcritical Hopf bifurcation point. This leads to a chaos within the system period doubling path. We then discuss the system controllability and present that the all chaotic oscillations fade away through the linear controller that we impose on the system.
文摘The instable combustion or oscillation combustion which occurs in three high capacity solid rocket motors using high energy composite propellant with finocyl grain is studied. The reasons of the acoustic combustion instability are also discussed. Three engineering methods that can eliminate combustion instability are proposed and discussed. The study shows that the combustion instability mainly depends on the propellant grain shape and nozzle structure. Some measures to reduce the acoustic energy and mass generation rate of combustion gas can be adopted. The test results indicate that the modified rocket motors can significantly eliminate the instable combustion and improve the motor internal ballistic performance.
文摘AIM: To ascertain the adequacy of the microsatellite instability (MSI) as a prognostic indicator by assessing MSI status of patients with double primary gastric and colorectal cancer (DPGCC).METHODS: Sixteen patients were studied, all of whom exhibited sporadic DPGCC, and had no family history of hereditary non-polyposis colorectal cancer, according to the Amsterdam criteria. A total of 32 cancers from 16DPGCC patients, and 216 single primary CRC, were assessed for MSI in 5 microsatellite loci, BAT25, BAT26,D2S123, D5S346, and D17S250.RESULTS: MSI was observed in 6 (37.5%) of 16 GC and 4 (25.0%) of 16 CRC. Thirty tumors (13.9%) out of 216single primary CRC and one tumor (16.7%) out of 6 double primary CRC were found to be microsatellite unstable. Of the 6 GC with MSI in DPGCC, 5 (31.3%) were MSI-high and one (6.3%) was MSI-low. In 5 of 16 DPGCC patients,the cancer recurred in or adjacent to the anastomosis or metastasized to the kidney or lung. The MSI-high DPGCC cases were associated with a younger age of onset (47.5 years vs 62.5 years), higher frequency of lymph node metastasis (100% vs 25%), and advanced Dukes stage (C, 100% vs 41.7%), as well as a higher frequency of recurrence or metastasis (100% vs 8.3%). Only recurrence or metastasis showed statistical significance by Fisher's exact test.CONCLUSION: Our data suggest that MSI may play an important role in the development of DPGCC, and that it may be used clinically as a molecular predictive marker for recurrence or late metastasis of DPGCC.
基金Department of Atomic Energy(DAE)for long-term support of this research,at present from the grant“Physics and Astronomy(Project Identification No.RTI4002)Department of Atomic Energy,Tata Institute of Fundamental Research”and partially from Grant No.JBR/2020/00039 of the Anusandhan National Research Foundation(ANRF),both agencies of the Government of Indiasupport from the ANRF through the J.C.Bose Fellowship Grant No.JCB/2017/000055 and Core Research Grant(CRG)Proposal Nos.ANRF/JBG/2025/000237/PS and CRG/2022/002782+1 种基金partial support from the Infosys-TIFR Leading Edge Research Grant(Cycle 2)the OSIRIS Consortium,consisting of UCLA and IST(Lisbon,Portugal),for providing access to the OSIRIS framework,which is work supported by Grant No.NSF ACI-1339893.
文摘Plasmas,the most common state of matter in the observable universe,are subject to instabilities of various types:hydrodynamic,magnetohydrodynamic,and electromagnetic.Our limited success in understanding these is due to the lack of direct experimental information on their origins and evolution.Here,we present direct spatially resolved measurements of the femtosecond evolution of the electromagnetic beam-driven instability that arises from the interaction of forward and return currents in an ultrahigh-intensity laser-produced plasma.We track its evolution from the initial linear stage to the later nonlinear stage by measuring the spatiotemporal evolution of the giant(megagauss)magnetic field created in the interaction process.Our experimental findings and numerical simulations are the first to indicate the observed instability triggered by the emission of electromagnetic radiation,like those known in the context of gravitational interaction,where the emission of gravitational radiation drives specific negative-energy modes in rotating black holes or neutron stars.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.12074399,12204500,and 12004403)the Key Projects of Intergovernmental International Scientific and Technological Innovation Cooperation(No.2021YFE0116700)+1 种基金the Shanghai Natural Science Foundation(No.20ZR1464400)the Shanghai Sailing Program(No.22YF1455300).
文摘The suppression of ablative Rayleigh–Taylor instability(ARTI)by a spatially modulated laser in inertial confinement fusion(ICF)is studied through numerical simulations.The results show that in the acceleration phase of ICF implosion,the growth of ARTI can be suppressed by using a short-wavelength spatially modulated laser.The ARTI growth rate decreases as the wavelength of the spatially modulated laser decreases,and ARTI is completely suppressed after a certain wavelength has been reached.A spatially uniform laser is introduced to keep the state of motion of the implosion fluid consistent,and it is found that the proportion of the spatially modulated laser required for complete suppression of ARTI decreases as the wavelength continues to decrease.We also optimize the spatial intensity distribution of the spatially modulated laser.In addition,as the duration of the spatially modulated laser decreases,the proportion required for completely suppressing ARTI increases,but the required energy decreases.When the perturbation wavenumber decreases,the wavelength of the spatially modulated laser required for complete suppression of ARTI becomes longer.In the case of multimode perturbation,ARTI can also be significantly suppressed by a spatially modulated laser,and the perturbation amplitude can be reduced to less than 10% of that without a spatially modulated laser.We believe that the conclusions drawn from our simulations can provide the basis for new approaches to control ARTI in ICF.
基金supported by the National Natural Science Foundation of China(62073172)the Natural Science Foundation of Jiangsu Province of China(BK20221329)。
文摘Reaction-diffusion systems are widely used to describe pattern formation,and various control strategies have been applied to reaction-diffusion systems to achieve control objectives such as boundary control,output feedback stabilization,and synchronization.However,controlling pattern dynamics in reaction-diffusion systems with fractional-order diffusion remains an unresolved problem.This paper presents a proportional-derivative(PD)control strategy for the Schnakenberg system with fractional-order diffusion and cross-diffusion.Theoretical analysis explores the amplitude equation near the Turing bifurcation threshold,determining the selection and stability of pattern formations.Numerical simulations demonstrate that the PD controller accomplishes the modification of pattern structures and suppression of Turing instability by adjusting only two control parameters.Additionally,it is found that for smaller fractional diffusion order,the region can accommodate more hexagonal and stripe patterns in space.This work contributes to the control of complex pattern dynamics and offers a new approach to enhancing stability in fractional reaction-diffusion systems.
基金Supported by the Meteorological Science and Technology Innovation Project of North China(HBXM202415)Research Project of the Meteorological Bureau of Inner Mongolia Autonomous Region(nmqxkjcx202311).
文摘Based on the conventional observation data,daily reanalysis data from NCAR/NCEP,and TBB data derived from FY-2G infrared cloud images in April 2018,a heavy snowfall weather process in central Inner Mongolia from April 4 to 6 in 2018 was analyzed.The results show that the low trough at 500 hPa,the southerly wind jet stream at 700 hPa,and the inverted trough on the ground were the main influencing systems causing this blizzard.The transportation of warm and humid air by the southerly wind jet stream at 700 hPa and intense water vapor convergence provided sufficient water vapor conditions for the blizzard,and the moist layer in the blizzard area was deep.The low-level MPV in the blizzard area was<0,and the atmosphere was in a conditional symmetric instability state.The coupling of the upper and lower-level jets induced strong ascending motion.With the invasion of cold air,a low-level cold pad was formed,so that the warm and humid air tilted upward.The secondary circulation updraft triggered by the wet Q vector system released the conditional symmetric instability energy,so that the sloping motion was more intense,and the heavy snowfall appeared.Meanwhile,there was a good correspondence relationship between the blizzard area and the large-value area of low-level wet Q vector divergence.The mesoscale cloud clusters continuously generating,merging,and moving eastward in Hetao area were the direct cause of this blizzard,and the TBB of the cloud clusters was≤-56℃.The blizzard happened in the the edge gradient and large-value area of TBB.
基金Project supported by the National Natural Science Foundation of China(Nos.12372214 and U2341231)。
文摘The Reynolds-averaged Navier-Stokes(RANS)technique enables critical engineering predictions and is widely adopted.However,since this iterative computation relies on the fixed-point iteration,it may converge to unexpected non-physical phase points in practice.We conduct an analysis on the phase-space characteristics and the fixed-point theory underlying the k-ε turbulence model,and employ the classical Kolmogorov flow as a framework,leveraging its direct numerical simulation(DNS)data to construct a one-dimensional(1D)system under periodic/fixed boundary conditions.The RANS results demonstrate that under periodic boundary conditions,the k-ε model exhibits only a unique trivial fixed point,with asymptotes capturing the phase portraits.The stability of this trivial fixed point is determined by a mathematically derived stability phase diagram,indicating the fact that the k-ε model will never converge to correct values under periodic conditions.In contrast,under fixed boundary conditions,the model can yield a stable non-trivial fixed point.The evolutionary mechanisms and their relationship with boundary condition settings systematically explain the inherent limitations of the k-ε model,i.e.,its deficiency in computing the flow field under periodic boundary conditions and sensitivity to boundary-value specifications under fixed boundary conditions.These conclusions are finally validated with the open-source code OpenFOAM.
基金supported by the National Natural Science Foundation of China(No.11972357)。
文摘Crossflow instability will be present when the vehicle has an angle of attack in hypersonic flow,and it might play a dominant role in hypersonic boundary layer transition.By far the mechanism of crossflow instability-induced hypersonic boundary layer transition is still out of understanding,although the large effort has been devoted.Upon this work,the overall roughness effect on instabilities in hypersonic flow was researched experimentally.Surface flush-mounted pressure sensors and infrared camera were employed to investigate the instability waves when different rough surfaces were deployed.The results reveal that the moderate surface roughness level on cone model can suppress the growth of crossflow instabilities at certain azimuthal angles in hypersonic flow.
基金support from the National Natural Science Foundation of China(No.12002372)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2022QNRC001)the Natural Science Foundation of Hunan Province,China(No.2021JJ40674)。
文摘The operational demands of a wide range significantly exacerbate combustion instability issues within ramjet combustor.To suppress combustion oscillations,an open-loop control system utilizing Linear Genetic Programming(LGP)has been developed for a full-scale annular ramjet combustor.The LGP is used to generate control laws that include multi-frequency forcing.These laws are then transformed into square waves to actuate the solenoid valve,which modulates the kerosene supply for open-loop control.The results show that the duty cycle has little effect on instability amplitude,whereas an increase in frequency leads to a remarked reduction in combustion amplitude.After five generations evolvements,the pressure amplitude is reduced by 40.6% under the optimal control law generated by LGP.Furthermore,the machine learning process is depicted using a proximity map of control law similarity,with the search pathway visualized by the steepest descent.All individuals go forward to the upper left corner of the map with the evolution process,terminating at the optimal individual of the fifth generation.
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金support from National Natural Science Foundation of China(Grant No.52474142)The National Science Fund for Distinguished Young Scholars(No.51925402),Chinathe China Postdoctoral Science Foundation(Grant No.2021M702049).
文摘Roof pre-fracture poses a considerable risk during the re-mining of residual coal above abandoned roadways,threatening the safety of the mining faces.This study employs a Winkler foundation beam model for mechanical analysis of roof structures and adopts a multivariate nonlinear analysis approach to explore the synergistic load-bearing effects within the'coal pillar-support-backfill body'system during the fill and re-mining processes above these roadways.The findings demonstrate that backfill mining significantly reduces stress concentrations in coal pillars and reduces excessive bending moments in roofs near abandoned roadways.The roof deflection equation incorporates three critical factors affecting stability during backfill mining:the width of the coal pillar(L_(3)),the working resistance of the support(q_(z)),and the elastic foundation coefficient of the backfill material(kcÞ.Under single-factor conditions,the impact sequence on roof stability in the coal pillar zone is·k_(c)>L_(3)>q_(z).Further,multivariate nonlinear analysis reveals the interactions within the'coal-support-backfill'structure,indicating that in terms of roof control,the interaction terms are ordered as L_(3)·k_(c)>q_(z)·k_(c)>L_(3)q_(z).Therefore,priority should be given to adjusting the coal pillar width and backfill strength,followed by modifications to the support resistance and backfill strength during the recovery of abandoned roadways.An improved understanding of these interactions will help optimize strategies for the recovery of residual coal through abandoned roadways,thereby enhancing the stability and safety of mining operations under complex geological conditions.
基金Youth Innovation Team of Shandong Higher Education Institutions,Grant/Award Number:2022KJ214Shandong Postdoctoral Science Foundation,Grant/Award Number:SDCXZG‐202303031+2 种基金China Postdoctoral Science Foundation,Grant/Award Number:2023M732109National Natural Science Foundation of China,Grant/Award Number:52209141Natural Science Foundation of Shandong Province,China,Grant/Award Number:ZR2021QE069。
文摘The deformation and failure of coal walls in front of a working face cause significant difficulties during mining operations.This study reveals the nonuniform distribution of bearing pressure in front of coal walls based on in situ monitoring data and numerical simulation.Therefore,an eccentric compression mechanical model was established to study the deformation and failure characteristics of a coal wall.The slenderness ratio of the compression bar is introduced to define coal walls.The results showed that instability failure occurs when λ>λ_(c) and material failure occurs when λ≤λ_(c).The instability failure-type coal wall spalling was related to the mining height,eccentricity of roof pressure,the horizontal force,and the reaction moment of the floor.The material failure-type coal wall spalling was related to the cohesion,the internal friction angle of the coal,the upper pressure,and the horizontal force of coal walls.Unstable and destructive coal wall peeling usually occurs at a height of 0.5–0.6 times the mining height,while material damage to coal wall peeling is determined to occur within the range of 0.4-0.6 times the mining depth.The findings contribute to the understanding of the deformation and failure of coal walls.
基金financial support provided by the National Key R&D Program of China(2022YFB3805700)the National Natural Science Foundation of China(Grant Nos.12072094 and 12172106)+1 种基金the open research fund of Suzhou Laboratory(No.SZLAB-1508-2024ZD016)the Self-Planned Task(No.SL20230101)of Songjiang Laboratory,Harbin Institute of Technology。
文摘Snap-through instability-based mechanical metamaterials(SIMMs)with bistability,multistability,negative stiffness,or excellent energy absorption and dissipation performance play an important role in various advanced functional applications.They can serve as energy absorbers,energy dampers,or mechanical memory and logic computing devices,while also providing amplified force output and faster response time in flexible robots,or implementing sensing functions combined with piezoelectric or triboelectric electricity.However,thus far,research on SIMMs that have non-fixed boundary constraints,proactive responsiveness,multi-physical field cross-coupling,and deep information processing capabilities is still facing significant challenges,potentially hindering the development and cross-field comprehensive applications of truly intelligent SIMMs.Our objective is to furnish a concise categorization of SIMMs and offer direction for innovative design and functional implementations.We have emphasized that the non-fixed boundary constraint will expand the design possibilities,while the use of stimulus-responsive materials and 4D printing technology will create novel opportunities for the design of SIMMs.These advancements are expected to achieve innovative mechanical properties and functions.
文摘GLOBAL GOVERNANCE AS AN INSTRUMENT FOR TRANSFORMING CHAOS INTO ORDERLY MULTIPOLARITY The current global geopolitical situation,marked by instability,the erosion of the post-WWII international order and the weakening of US unipolar dominance,requires joint efforts by major international actors and the wider international community to establish a functional international order for the twenty-first century.
基金supported by the following grants:Agence nationale de la recherche(ANR)grant R23192NNInstitut national du cancer(INCa)grant PLBIO22-217+2 种基金Association pour la Recherche sur le Cancer(ARC)grant ARCPJA2021060003753 and PRTK 2021-025Ligue contre le cancer Grand-OuestAllocations de Recherche Doctorale région Bretagne/Inserm PhD fellowship.
文摘DIS3 is the main catalytic subunit of the nuclear RNA exosome,a complex playing a crucial role in RNA processing and the degradation of various noncoding RNA substrates.In mice,DIS3 is essential for genomic rearrangements during B cell development,but its role in terminal plasma cell(PC)differentiation has not been explored.Although DIS3 gene alterations are frequent in multiple myeloma(MM),a PC malignancy,their molecular impact remains poorly understood.In this study,we developed an antisense oligonucleotide strategy to knock down DIS3 expression in a well-characterized model of human PC differentiation.Reducing DIS3 expression systematically led to decreased B cell proliferation and impaired PC differentiation with lower levels of switched immunoglobulin secretion.Transcriptome analyses confirmed alterations in the proliferation and differentiation programs,alongside an accumulation of noncoding RNAs.Notably,centromere-associated noncoding RNAs were highly sensitive to DIS3 activity,and their accumulation in DIS3-deficient cells,either as transcripts or DNA-associated RNAs,correlated with the mislocalization of the centromere-specific histone variant CENP-A.We finally observed reduced physiological DNA recombination and somatic hypermutation but increased genomic instability in DIS3-deficient cells,in agreement with the higher levels of IGH translocations observed in our large cohort of DIS3-mutant MM patients.Together,these results underscore the essential role of DIS3 in regulating B cell proliferation,DNA recombination,and physiological or malignant PC differentiation in humans.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,China(No.2021B1515140007).
文摘The rapid cycling synchrotron(RCS)at the China spallation neutron source operates as a high-intensity proton accelerator.The coupled bunch instability was observed during RCS beam commissioning,which significantly limited the beam power.To investigate the dynamics of instability under an increased beam power,a pulsed octupole magnet with a gradient of 900 T/m^(3) was developed.The magnet system integrated an octupole magnet with a pulsed power supply.The field was carefully measured to examine the performance before its installation into the tunnel.After the installation of the magnets,beam measurements were performed to confirm the effectiveness of the instability mitigation on an actual proton beam.The measurement results show that the instability can be suppressed using the pulsed octupole magnet,particularly at the highenergy stage in an acceleration cycle,meeting the requirements for stable operation of the accelerator.Additionally,when the instability is completely suppressed through chromaticity optimization,octupole magnets can significantly enhance the RCS transmission efficiency,which is crucial for controlling beam loss.The pulsed octupole magnet offers significant progress in beam stability in the RCS,providing valuable experience for further beam power enhancement.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
