A proteomic landscape of pharmacologic perturbations for functional relevance

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

A generalization of Banach's lemma and its applications to perturbations of bounded linear operators

Let X be a Banach space and let P:X→X be a bounded linear operator.Using an algebraic inequality on the spectrum of P,we give a new sufficient condition that guarantees the existence of(I-P)^(-1) as a bounded linear operator on X,and a bound on its spectral radius is also obtained.This generalizes the classic Banach lemma.We apply the result to the perturbation analysis of general bounded linear operators on X with commutative perturbations.

Volcanically Driven Terrestrial Environmental Perturbations during the Carnian Pluvial Episode in the Eastern Tethys

The Carnian Pluvial Episode(CPE)fingerprints global environmental perturbations and biological extinction on land and oceans and is potentially linked to the Wrangellia Large Igneous Province(LIP).However,the correlation between terrestrial environmental changes and Wrangellia volcanism in the Ordos Basin during the CPE remains poorly understood.Records of negative carbon isotopic excursions(NCIEs),mercury(Hg),Hg/TOC,and Hg enrichment factor(HgEF)from oil shales in a large-scale terrestrial Ordos Basin in the Eastern Tethys were correlated with marine and other terrestrial successions.The three significant NCIEs in the study section were consistently correlated with those in the CPE successions of Europe,the UK,and South and North China.The U-Pb geochronology indicates a Ladinian-Carnian age for the Chang 7 Member.A comprehensive overview of the geochronology,NCIE correlation,and previous bio-and chronostratigraphic frameworks shows that the Ladinian-Carnian boundary is located in the lower part of Chang 7 in the Yishicun section.HgEF may be a more reliable proxy for tracing volcanic eruptions than the Hg/TOC ratio because the accumulation rates of TOC content largely vary in terrestrial and marine successions.The records of Hg,Hg/TOC,HgEF,and NCIEs in the Ordos Basin aligned with Carnian successions worldwide and were marked by similar anomalies,indicating a global response to the Wrangellia LIP during the CPE.Anoxia,a warm-humid climate,enhancement of detrital input,and NCIEs are synchronous with the CPE interval in the Ordos Basin,which suggests that the CPE combined with the regional Qinling Orogeny should dominate the enhanced rate of terrigenous input and paleoenvironmental evolution in the Ordos Basin.

Investigation on the roles of equilibrium toroidal rotation during edge-localized mode mitigated by resonant magnetic perturbations

The effects of equilibrium toroidal rotation during edge-localized mode(ELM)mitigated by resonant magnetic perturbation(RMP)are studied with the experimental equilibria of the EAST tokamak based on the four-field model in the BOUT++code.As the two main parameters to determine the toroidal rotation profiles,the rotation shear and magnitudes were separately scanned to investigate their roles in the impact of RMPs on peeling-ballooning(P-B)modes.On one hand,the results show that strong toroidal rotation shear is favorable for the enhancement of the self-generated E×B shearing rate<ω_(E×B)>with RMPs,leading to significant ELM mitigation with RMP in the stronger toroidal rotation shear region.On the other hand,toroidal rotation magnitudes may affect ELM mitigation by changing the penetration of the RMPs,more precisely the resonant components.RMPs can lead to a reduction in the pedestal energy loss by enhancing the multimode coupling in the turbulence transport phase.The shielding effects on RMPs increase with the toroidal rotation magnitude,leading to the enhancement of the multimode coupling with RMPs to be significantly weakened.Hence,the reduction in pedestal energy loss by RMPs decreased with the rotation magnitude.In brief,the results show that toroidal rotation plays a dual role in ELM mitigation with RMP by changing the shielding effects of plasma by rotation magnitude and affecting<ω_(E×B)>by rotation shear.In the high toroidal rotation region,toroidal rotation shear is usually strong and hence plays a dominant role in the influence of RMP on P-B modes,whereas in the low rotation region,toroidal rotation shear is weak and has negligible impact on P-B modes,and the rotation magnitude plays a dominant role in the influence of RMPs on the P-B modes by changing the field penetration.Therefore,the dual role of toroidal rotation leads to stronger ELM mitigation with RMP,which may be achieved both in the low toroidal rotation region and the relatively high rotation region that has strong rotational shear.

Growth and Interactions of Multi-Source Perturbations in Convection-Allowing Ensemble Forecasts

This study investigated the growth of forecast errors stemming from initial conditions(ICs),lateral boundary conditions(LBCs),and model(MO)perturbations,as well as their interactions,by conducting seven 36 h convectionallowing ensemble forecast(CAEF)experiments.Two cases,one with strong-forcing(SF)and the other with weak-forcing(WF),occurred over the Yangtze-Huai River basin(YHRB)in East China,were selected to examine the sources of uncertainties associated with perturbation growth under varying forcing backgrounds and the influence of these backgrounds on growth.The perturbations exhibited distinct characteristics in terms of temporal evolution,spatial propagation,and vertical distribution under different forcing backgrounds,indicating a dependence between perturbation growth and forcing background.A comparison of the perturbation growth in different precipitation areas revealed that IC and LBC perturbations were significantly influenced by the location of precipitation in the SF case,while MO perturbations were more responsive to convection triggering and dominated in the WF case.The vertical distribution of perturbations showed that the sources of uncertainties and the performance of perturbations varied between SF and WF cases,with LBC perturbations displaying notable case dependence.Furthermore,the interactions between perturbations were considered by exploring the added values of different source perturbations.For the SF case,the added values of IC,LBC,and MO perturbations were reflected in different forecast periods and different source uncertainties,suggesting that the combination of multi-source perturbations can yield positive interactions.In the WF case,MO perturbations provided a more accurate estimation of uncertainties downstream of the Dabie Mountain and need to be prioritized in the research on perturbation development.

Suppression of Plasma Bubbles over South America under Weak Geomagnetic Perturbations

During a long-term Equatorial Plasma Bubbles(EPBs)occurrence between October 2020 and March 2021,a significant EPB suppression event was identified on November 22 and the observations from multi-instrument have been utilized to investigate this event.Global-scale Observations of the Limb and Disk(GOLD)satellite observed prominent EPBs between 23:40 UT and 23:55 UT during the long-term occurrence days.However,no dark stripes representing EPBs were observed on November 22,and the Equatorial Ionization Anomaly(EIA)structure remained intact.The Total Electron Content(TEC)maps show that these EPBs appeared in the region between 35°W and 65°W longitudes and the magnitudes of the TEC loss in EPBs regions were about 20 TECU.Except for 22 November,the S4 index was consistently greater than 0.6 throughout November,indicating significant ionospheric scintillation.The Rate Of TEC Index(ROTI)maps revealed that the spatial extent and intensity of EPBs increased after their suppression,and the EPBs were locally generated.The swarm electron density measurements indicated that the variation amplitudes of EPBs at 510 km altitude were approximately 3 to 5 times larger than that at 460 km altitude.The impact region of EPBs at 510 km was between 15°S and 20°N latitudes,while at 460 km,it was between 0°and 17°N latitudes.During the period of EPB suppression,the average h’f at three ionosonde stations decreased by about 50 km,and the vertical drift velocity(V z)approached~0 m/s while it was more than 20 m/s during the long-term occurrence.

Cover Enhancement Method for Audio Steganography Based on Universal Adversarial Perturbations with Sample Diversification

Steganography techniques,such as audio steganography,have been widely used in covert communication.However,the deep neural network,especially the convolutional neural network(CNN),has greatly threatened the security of audio steganography.Besides,existing adversarial attacks-based countermeasures cannot provide general perturbation,and the trans-ferability against unknown steganography detection methods is weak.This paper proposes a cover enhancement method for audio steganography based on universal adversarial perturbations with sample diversification to address these issues.Universal adversarial perturbation is constructed by iteratively optimizing adversarial perturbation,which applies adversarial attack tech-niques,such as Deepfool.Moreover,the sample diversification strategy is designed to improve the transferability of adversarial perturbations in black-box attack scenarios,where two types of common audio-processing operations are considered,including noise addition and moving picture experts group audio layer III(MP3)compression.Furthermore,the perturbation ensemble method is applied to further improve the attacks’transferability by integrating perturbations of different detection networks with heterogeneous architec-tures.Consequently,the single universal adversarial perturbation can enhance different cover audios against a CNN-based detection network.Extensive experiments have been conducted,and the results demonstrate that the average missed-detection probabilities of the proposed method are higher than those of the state-of-the-art methods by 7.3%and 16.6%for known and unknown detection networks,respectively.It verifies the efficiency and transferability of the proposed methods for the cover enhancement of audio steganography.

The Influence of Arctic Sea Ice Concentration Perturbations on Subseasonal Predictions of North Atlantic Oscillation Events

The influence of Arctic sea ice concentration (SIC) on the subseasonal prediction of the North Atlantic Oscillation (NAO) event is investigated by utilizing the Community Atmospheric Model version 4. The optimal Arctic SIC perturbations which exert the greatest influence on the onset of an NAO event from a lead of three pentads (15 days) are obtained with a conditional nonlinear optimal perturbation approach. Numerical results show that there are two types of optimal Arctic SIC perturbations for each NAO event, with one weakening event (marked as type-1) and another strengthening event (marked as type-2). For positive NAO events, type-1 optimal SIC perturbations mainly show positive SIC anomalies in the Greenland, Barents, and Okhotsk Seas, while type-2 perturbations mainly feature negative SIC anomalies in these regions. For negative NAO events, the optimal SIC perturbations have almost opposite patterns to those in positive events, although there are some differences among these SIC perturbations due to different atmospheric initial conditions. Further diagnosis reveals that the optimal Arctic SIC perturbations first modify the surface turbulent heat flux and the temperature in the lower troposphere via diabatic processes. Afterward, the temperature in the low troposphere is mainly affected by dynamic advection. Finally, potential vorticity advection plays a crucial role in the 500-hPa geopotential height prediction in the northern North Atlantic sector during pentad 4, which influences NAO event prediction. These results highlight the importance of Arctic SIC on NAO event prediction and the spatial characteristics of the SIC perturbations may provide scientific support for target observations of SIC in improving NAO subseasonal predictions.

Boundedness Types of Perturbations on the Growth of Semigroups

We study types of boundedness of a semigroup on a Banach space in terms of the Cesáro-average and the behavior of the resolvent at the origin and also exhibit a characterization of type Hille-Yosida for the generators of ϕj-bounded strongly continuous semigroups. Furthermore, these results are used to investigate the effect of the Perturbation on the type of the growth of sequences.

Advances in experiments and numerical simulations on the effects of stress perturbations on fault slip

Laboratory experiments and numerical simulations on rock friction perturbations,an important means for understanding the mechanism and influencing factors of stress-triggered earthquakes,are of great significance for studying earthquake mechanisms and earthquake hazard analysis.We reviews the experiments and numerical simulations on the effects of stress perturbations on fault slip,and the results show that stress perturbations can change fault stress and trigger earthquakes.The Coulomb failure criterion can shed light on some questions about stress-triggering earthquakes but cannot explain the time dependence of earthquake triggering nor be used to investigate the effect of heterogeneous stress perturbations.The amplitude and period are important factors affecting the correlation between stress perturbation and fault instability.The effect of the perturbation period on fault instability is still controversial,and the effect of the high-frequency perturbation on earthquakes may be underestimated.Normal and shear stress perturbation can trigger fault instability,but their effects on fault slip differ.It is necessary to distinguish whether the stress perturbation is dominated by shear or normal stress change when it triggers fault instability.Fault tectonic stress plays a decisive effect on the mode of fault instability and earthquake magnitude.Acoustic emission activity can reflect the changes in fault stress and the progression of fault nucleation,and identify the meta-instability stage and precursor of fault instability,providing a reference for earthquake prediction.

Growth of ablative Rayleigh-Taylor instability induced by time-varying heat-flux perturbation

The evolution of ablative Rayleigh–Taylor instability(ARTI)induced by single-mode stationary and time-varying perturbations in heat flux is studied numerically in two dimensions.Compared with the stationary case,time-varying heat-flux perturbation mitigates ARTI growth because of the enhanced thermal smoothing induced by the wave-like traveling heat flux.A resonance is found to form when the phase velocity of the heat-flux perturbation matches the average sound speed in the ablation region.In the resonant regime,the coherent density and temperature fluctuations enhance the electron thermal conduction in the ablation region and lead to larger ablation pressure and effective acceleration,which consequently yield higher linear growth rate and saturated bubble velocity.The enhanced effective acceleration offers increased implosion velocity but can also compromise the integrity of inertial confinement fusion shells by causing faster ARTI growth.

THE SUPERCLOSENESS OF THE FINITE ELEMENT METHOD FOR A SINGULARLY PERTURBED CONVECTION-DIFFUSION PROBLEM ON A BAKHVALOV-TYPE MESH IN 2D

For singularly perturbed convection-diffusion problems,supercloseness analysis of the finite element method is still open on Bakhvalov-type meshes,especially in the case of 2D.The difficulties arise from the width of the mesh in the layer adjacent to the transition point,resulting in a suboptimal estimate for convergence.Existing analysis techniques cannot handle these difficulties well.To fill this gap,here a novel interpolation is designed delicately for the smooth part of the solution,bringing about the optimal supercloseness result of almost order 2 under an energy norm for the finite element method.Our theoretical result is uniform in the singular perturbation parameterεand is supported by the numerical experiments.

Comparison of transport coefficients before and after density pump-out induced by resonant magnetic perturbation using a BOUT++ six-field model on the EAST tokamak

Many experiments have demonstrated that resonant magnetic perturbation(RMP) can affect the turbulent transport at the edge of the tokamak. Through the Experimental Advanced Superconducting Tokamak(EAST) density modulation experiment, the particle transport coefficients were calculated using the experimental data, and the result shows that the particle transport coefficients increase with RMP. In this study, the six-field two-fluid model in BOUT++ is used to simulate the transport before and after density pump-out induced by RMP,respectively referred as the case without RMP and the case with RMP. In the linear simulations,the instabilities generally decreases for cases with RMP. In the nonlinear simulation, ELM only appears in the case without RMP. Additionally, the particle transport coefficient was analyzed,and the result shows that the particle transport coefficient becomes larger for the case with RMP,which is consistent with the experimental conclusion. Moreover, its magnitude is comparable to the results calculated from experimental data.

An Initial Perturbation Method for the Multiscale Singular Vector in Global Ensemble Prediction

Ensemble prediction is widely used to represent the uncertainty of single deterministic Numerical Weather Prediction(NWP) caused by errors in initial conditions(ICs). The traditional Singular Vector(SV) initial perturbation method tends only to capture synoptic scale initial uncertainty rather than mesoscale uncertainty in global ensemble prediction. To address this issue, a multiscale SV initial perturbation method based on the China Meteorological Administration Global Ensemble Prediction System(CMA-GEPS) is proposed to quantify multiscale initial uncertainty. The multiscale SV initial perturbation approach entails calculating multiscale SVs at different resolutions with multiple linearized physical processes to capture fast-growing perturbations from mesoscale to synoptic scale in target areas and combining these SVs by using a Gaussian sampling method with amplitude coefficients to generate initial perturbations. Following that, the energy norm,energy spectrum, and structure of multiscale SVs and their impact on GEPS are analyzed based on a batch experiment in different seasons. The results show that the multiscale SV initial perturbations can possess more energy and capture more mesoscale uncertainties than the traditional single-SV method. Meanwhile, multiscale SV initial perturbations can reflect the strongest dynamical instability in target areas. Their performances in global ensemble prediction when compared to single-scale SVs are shown to(i) improve the relationship between the ensemble spread and the root-mean-square error and(ii) provide a better probability forecast skill for atmospheric circulation during the late forecast period and for short-to medium-range precipitation. This study provides scientific evidence and application foundations for the design and development of a multiscale SV initial perturbation method for the GEPS.

Generalized nth-Order Perturbation Method Based on Loop Subdivision Surface Boundary Element Method for Three-Dimensional Broadband Structural Acoustic Uncertainty Analysis

In this paper,a generalized nth-order perturbation method based on the isogeometric boundary element method is proposed for the uncertainty analysis of broadband structural acoustic scattering problems.The Burton-Miller method is employed to solve the problem of non-unique solutions that may be encountered in the external acoustic field,and the nth-order discretization formulation of the boundary integral equation is derived.In addition,the computation of loop subdivision surfaces and the subdivision rules are introduced.In order to confirm the effectiveness of the algorithm,the computed results are contrasted and analyzed with the results under Monte Carlo simulations(MCs)through several numerical examples.

A novel algorithm for evaluating cement azimuthal density based on perturbation theory in horizontal well

Cement density monitoring plays a vital role in evaluating the quality of cementing projects,which is of great significance to the development of oil and gas.However,the presence of inhomogeneous cement distribution and casing eccentricity in horizontal wells often complicates the accurate evaluation of cement azimuthal density.In this regard,this paper proposes an algorithm to calculate the cement azimuthal density in horizontal wells using a multi-detector gamma-ray detection system.The spatial dynamic response functions are simulated to obtain the influence of cement density on gamma-ray counts by the perturbation theory,and the contribution of cement density in six sectors to the gamma-ray recorded by different detectors is obtained by integrating the spatial dynamic response functions.Combined with the relationship between gamma-ray counts and cement density,a multi-parameter calculation equation system is established,and the regularized Newton iteration method is employed to invert casing eccentricity and cement azimuthal density.This approach ensures the stability of the inversion process while simultaneously achieving an accuracy of 0.05 g/cm^(3) for the cement azimuthal density.This accuracy level is ten times higher compared to density accuracy calculated using calibration equations.Overall,this algorithm enhances the accuracy of cement azimuthal density evaluation,provides valuable technical support for the monitoring of cement azimuthal density in the oil and gas industry.

Wavelet Multi-Resolution Interpolation Galerkin Method for Linear Singularly Perturbed Boundary Value Problems

In this study,a wavelet multi-resolution interpolation Galerkin method(WMIGM)is proposed to solve linear singularly perturbed boundary value problems.Unlike conventional wavelet schemes,the proposed algorithm can be readily extended to special node generation techniques,such as the Shishkin node.Such a wavelet method allows a high degree of local refinement of the nodal distribution to efficiently capture localized steep gradients.All the shape functions possess the Kronecker delta property,making the imposition of boundary conditions as easy as that in the finite element method.Four numerical examples are studied to demonstrate the validity and accuracy of the proposedwavelet method.The results showthat the use ofmodified Shishkin nodes can significantly reduce numerical oscillation near the boundary layer.Compared with many other methods,the proposed method possesses satisfactory accuracy and efficiency.The theoretical and numerical results demonstrate that the order of theε-uniform convergence of this wavelet method can reach 5.

Adaptive Optimal Output Regulation of Interconnected Singularly Perturbed Systems With Application to Power Systems

This article studies the adaptive optimal output regulation problem for a class of interconnected singularly perturbed systems(SPSs) with unknown dynamics based on reinforcement learning(RL).Taking into account the slow and fast characteristics among system states,the interconnected SPS is decomposed into the slow time-scale dynamics and the fast timescale dynamics through singular perturbation theory.For the fast time-scale dynamics with interconnections,we devise a decentralized optimal control strategy by selecting appropriate weight matrices in the cost function.For the slow time-scale dynamics with unknown system parameters,an off-policy RL algorithm with convergence guarantee is given to learn the optimal control strategy in terms of measurement data.By combining the slow and fast controllers,we establish the composite decentralized adaptive optimal output regulator,and rigorously analyze the stability and optimality of the closed-loop system.The proposed decomposition design not only bypasses the numerical stiffness but also alleviates the high-dimensionality.The efficacy of the proposed methodology is validated by a load-frequency control application of a two-area power system.

Ionospheric perturbations before Pu’er earthquake observed on DEMETER

A destructive shock with magnitude of 6.3 occurred on 2 June 2007 at 21h34min56s UT in Pu’er region (23.0°N, 101.1°E), Yunnan Province, China. The data from DEMETER satellite during the period from 23 May to 2 June, i.e., ten days before the earthquake and one day just on the day of earthquake occurrence, were analyzed. Among the 284 orbits of DEMETER during the period, 29 orbits with the trace passing through the region within 1 888 km from the epicenter were selected to be studied. Seven anomalous events were found on the dataset of the seven orbits among the 29 ones. There existed synchronous perturbations on the variations of the spectrogram of the electric field and the variations of the density and temperature of the ions and electron, in contrast with the variations of its surround- ing area. And five events appeared in the space within 1 888 km from the epicenter while the other two were out of the studied area. Electrostatic turbulences were also recorded with the synchronous perturbations with that in the electron density and ions density in plasma in the region near the epicenter in the five events, which seems to sug- gest that there be some physical relation between these events and the preparation processes of Pu’er earthquake.

Ensemble Forecasts of Tropical Cyclone Track with Orthogonal Conditional Nonlinear Optimal Perturbations

This paper preliminarily investigates the application of the orthogonal conditional nonlinear optimal perturbations(CNOPs)–based ensemble forecast technique in MM5(Fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model). The results show that the ensemble forecast members generated by the orthogonal CNOPs present large spreads but tend to be located on the two sides of real tropical cyclone(TC) tracks and have good agreements between ensemble spreads and ensemble-mean forecast errors for TC tracks. Subsequently, these members reflect more reasonable forecast uncertainties and enhance the orthogonal CNOPs–based ensemble-mean forecasts to obtain higher skill for TC tracks than the orthogonal SVs(singular vectors)–, BVs(bred vectors)– and RPs(random perturbations)–based ones. The results indicate that orthogonal CNOPs of smaller magnitudes should be adopted to construct the initial ensemble perturbations for short lead–time forecasts, but those of larger magnitudes should be used for longer lead–time forecasts due to the effects of nonlinearities. The performance of the orthogonal CNOPs–based ensemble-mean forecasts is case-dependent,which encourages evaluating statistically the forecast skill with more TC cases. Finally, the results show that the ensemble forecasts with only initial perturbations in this work do not increase the forecast skill of TC intensity, which may be related with both the coarse model horizontal resolution and the model error.