Effects Of Perturbations Research Articles

The Effect of Repetitive Mechanical Perturbations on Lower Limb Symmetry in Postural Control

Background: Postural symmetry ensures balanced alignment and equal weight distribution, promoting optimal function and minimizing stress on muscles and joints. This study aimed to evaluate lower limb movement symmetry in response to mechanical perturbations. Methods: Twelve healthy young women were subjected to mechanical perturbation tests while standing on the Motek GRAIL system treadmill. Maximum values of kinematic and kinetic parameters and symmetry indices were counted to compare the responses of dominant and non-dominant limbs. Results: The study identified symmetrical and asymmetrical features in lower limb dynamics. Symmetry nearness was observed in the ankle joint angle (SI = 0.03), the hip torque (SI = 0.03), and the vertical component of the ground reaction force (SI = 0.04). However, significant asymmetries were found in the medio-lateral component of the ground reaction force (SI = 1.84), ankle torque (SI = 0.23), knee torque (SI = 0.19), hip angle (SI = 0.15), and knee angle (SI = 0.08). The anterior–posterior component of the ground reaction force (SI = 0.14) showed asymmetry but was not statistically significant. Conclusions: Perturbations impact lower limb dynamics, revealing dominance- and joint-specific asymmetries. Bilateral assessment is crucial for understanding postural control, guiding rehabilitation to restore symmetry, and reducing the risk of injuries, falls, and musculoskeletal strain, particularly in athletes and older adults. These findings emphasize the value of symmetry indices in optimizing therapy and prevention strategies.

Fock-Space Delocalization and the Emergence of the Porter-Thomas Distribution from Dual-Unitary Dynamics

The chaotic dynamics of quantum many-body systems are expected to quickly randomize any structured initial state, delocalizing it in the Fock space. In this Letter, we study the spreading of an initial product state in Hilbert space under dual-unitary dynamics, captured by the inverse participation ratios and the distribution of overlaps (bit-string probabilities). We consider the self-dual kicked Ising model, a minimal model of many-body quantum chaos that can be seen as either a periodically driven Floquet model or a dual-unitary quantum circuit. Both analytically and numerically, we show that the inverse participation ratios rapidly approach their ergodic values, corresponding to those of Haar random states, and establish the emergence of the Porter-Thomas distribution for the overlap distribution. Importantly, this convergence happens exponentially fast in time, with a timescale that is independent of system size. We inspect the effect of local perturbations that break dual unitarity and show a slowdown of the spreading in Fock space, indicating that dual-unitary circuits are maximally efficient at preparing random states. Our Letter establishes bridges between the dynamics of many-body systems and random matrix theory through the time evolution of structured initial states and finds natural applications in demonstrating a quantum advantage in random sampling and in benchmarking quantum devices. Published by the American Physical Society 2025

Antibiotics change the population growth rate heterogeneity and morphology of bacteria.

A better understanding of the system-level effects of antibiotics on bacterial cells is essential to address the growing challenge of antibiotic resistance. Utilising Multipad Agarose Plate (MAP) platforms, we monitor the growth rate and cell morphology of three clinically relevant species (E.coli, S.aureus and P.aeruginosa) following exposure to 14 antibiotics across 11 concentrations (31 microbe-antibiotic combinations in total). Our results reveal a consistent increase in population growth rate heterogeneity (PGRH) as drug concentrations approach the minimum inhibitory concentration (MIC). Strikingly, the magnitude of this heterogeneity correlates with the functional distance between the ribosome and the specific cellular processes targeted by the antibiotics. Among the seven antibiotic classes studied, protein synthesis inhibitors and disruptors cause the lowest PGRH, while heterogeneity progressively increases with RNA synthesis inhibitors, DNA replication inhibitors, cell membrane disruptors and cell wall synthesis inhibitors. Because the ribosome is central to growth rate control, we hypothesize that heterogeneity might arise at the system level as a result of the propagation of damage to protein synthesis. Low heterogeneity is desirable from a clinical perspective, as high heterogeneity is often associated with persistence and treatment survival. Additionally, we observed a strong correlation between morphological alterations and growth inhibition across all antibiotics and species tested. This led to the development of a novel morphological parameter, MOR50, which enables rapid estimation of MIC for antibiotic susceptibility testing (AST) with a single snapshot after just 2.5 hours of incubation. In addition to introducing a novel, resource-efficient and rapid AST method, our findings shed new light on the system-level effects of antibiotic perturbations on bacteria, which might inform treatment design.

Effect of Insect Exclusion and Microbial Perturbation on Piglet Mass Loss and Total Body Score

Recent conceptual and empirical developments in decomposition research have highlighted the intricate dynamics within necrobiome communities and the roles of various decay drivers. Yet the interactions between these factors and their regulatory mechanisms remain relatively unexplored. A comprehensive understanding of this facet of decomposition science is important, given its broad applicability across ecological and forensic disciplines, and current lack of research which investigates the inter-dependencies between two critical components of the necrobiome (the microbiome and insect activity), and the consequences of this interdependency on mass loss and total body score. Here we investigated the relationships among these key aspects of the decay process. We experimentally manipulated these variables by physically excluding insects and chemically perturbing the external microbiome of piglet (Sus scrofa) carcasses and quantified the effects on mass loss and total body score, as well as insect pre-appearance interval and colonisation. We found that piglets in the insect excluded and microbially perturbed treatment groups exhibited a significant delay in reaching 50+% of mass loss compared with control piglets with insect access and intact microbiome. However, only remains with insects excluded displayed a significantly slower rate of total mass loss throughout the majority of the experiment and remained a significantly higher mass at the endpoint of 11,000 accumulative degree hours. Additionally, all insect excluded and microbially perturbed treatment groups displayed significantly lower total body scores compared to control piglets at corresponding time points. We also observed a significant delay in insect pre-appearance interval and colonisation for piglets with perturbed microbiomes compared to control piglets. Our findings demonstrate the significance of interacting components of the necrobiome, and the power of manipulative experiments in revealing causal relationships between biota and decomposition rates. These considerations are paramount for developing accurate post-mortem interval estimations and a comprehensive understanding of ecological processes during decomposition.

Sensitivities of Large Eddy Simulations of Aerosol Plume Transport and Cloud Response

AbstractCloud responses to surface‐based sources of aerosol perturbation partially depend on how turbulent transport of the aerosol to cloud base affects the spatial and temporal distribution of aerosol. Here, scenarios of plume injection below a marine stratocumulus cloud are modeled using large eddy simulations coupled to a prognostic bulk aerosol and cloud microphysics scheme. Both passive plumes, consisting of an inert tracer, and active plumes are investigated, where the latter are representative of saltwater droplet plumes such as have been proposed for marine cloud brightening. Passive plume scenarios show higher in‐plume cloud brightness (relative to out‐of‐plume) due to the predominant transport of the passive plume tracer from the near‐surface to the cloud layer within updrafts. These updrafts rise into brighter areas within the cloud deck, even in the absence of an aerosol perturbation associated with an active plume. Comparing albedo at in‐plume to out‐of‐plume locations associates the inert plume with the brightest cloud locations, without any causal effect of the plume on the cloud. Numerical sensitivities are first assessed to establish a suitable model configuration. Then sensitivity to particle injection rate is investigated. Trade‐offs are identified between the number of injected particles and the suppressive effect of droplet evaporation on plume loft and spread. Furthermore, as the near‐field in‐plume brightening effect does not depend significantly on injection rate given a suitable definition of perturbed versus unperturbed regions of the flow, plume area is a key controlling factor on the overall cloud brightening effect of an aerosol perturbation.

Merging metabolic modeling and imaging for screening therapeutic targets in colorectal cancer

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as a crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC–CAF crosstalk.

A first principles study of convection cells to shear flow instability in 2D Yukawa liquids driven by Reynolds stress

The stability of kinetic-level convection cells (wherein the magnitude of macroscopic and microscopic velocities are of same order) is studied in a two-dimensional Yukawa liquid under the effect of microscopic velocity perturbations. Our numerical experiments demonstrate that for a given system aspect ratio viz., the ratio of system length to its height and number of convective rolls initiated , the fate of the convective cells is decided by . For , Reynolds stress is found to be self-consistently generated and sustained, which results in tilting of convection cells, eventually leading to shear flow generation, whereas for , parallel shear flow is found to be untenable. An unambiguous quantitative connection between Reynolds stress and the onset of shear flow using particle-level data is established without free parameters. The growth rate of the instability, the role of frictional forces, generalization of our findings and the possibility of realizing the same in experiments are also discussed.

Electric-field manipulation of magnetization in an insulating dilute ferromagnet through piezoelectromagnetic coupling

The electric field control of magnetization is of significant interest in materials science due to potential applications in many devices such as sensors, actuators, and magnetic memories. Here, we report magnetization changes generated by an electric field in ferromagnetic Ga1−xMnxN grown by molecular beam epitaxy. Two classes of phenomena have been revealed. First, over a wide range of magnetic fields, the magnetoelectric signal is odd in the electric field and reversible. Employing a macroscopic spin model and atomistic Landau-Lifshitz-Gilbert theory with Langevin dynamics, we demonstrate that the magnetoelectric response results from the inverse piezoelectric effect that changes the trigonal single-ion magnetocrystalline anisotropy. Second, in the metastable regime of ferromagnetic hystereses, the magnetoelectric effect becomes non-linear and irreversible in response to a time-dependent electric field, which can reorient the magnetization direction. Interestingly, our observations are similar to those reported for another dilute ferromagnetic semiconductor Crx(Bi1−ySby)1−xTe3, in which magnetization was monitored as a function of the gate electric field. Those results constitute experimental support for theories describing the effects of time-dependent perturbation upon glasses far from thermal equilibrium in terms of an enhanced effective temperature.

BuDDI: Bulk Deconvolution with Domain Invariance to predict cell-type-specific perturbations from bulk.

While single-cell experiments provide deep cellular resolution within a single sample, some single-cell experiments are inherently more challenging than bulk experiments due to dissociation difficulties, cost, or limited tissue availability. This creates a situation where we have deep cellular profiles of one sample or condition, and bulk profiles across multiple samples and conditions. To bridge this gap, we propose BuDDI (BUlk Deconvolution with Domain Invariance). BuDDI utilizes domain adaptation techniques to effectively integrate available corpora of case-control bulk and reference scRNA-seq observations to infer cell-type-specific perturbation effects. BuDDI achieves this by learning independent latent spaces within a single variational autoencoder (VAE) encompassing at least four sources of variability: 1) cell type proportion, 2) perturbation effect, 3) structured experimental variability, and 4) remaining variability. Since each latent space is encouraged to be independent, we simulate perturbation responses by independently composing each latent space to simulate cell-type-specific perturbation responses. We evaluated BuDDI's performance on simulated and real data with experimental designs of increasing complexity. We first validated that BuDDI could learn domain invariant latent spaces on data with matched samples across each source of variability. Then we validated that BuDDI could accurately predict cell-type-specific perturbation response when no single-cell perturbed profiles were used during training; instead, only bulk samples had both perturbed and non-perturbed observations. Finally, we validated BuDDI on predicting sex-specific differences, an experimental design where it is not possible to have matched samples. In each experiment, BuDDI outperformed all other comparative methods and baselines. As more reference atlases are completed, BuDDI provides a path to combine these resources with bulk-profiled treatment or disease signatures to study perturbations, sex differences, or other factors at single-cell resolution.

Event‐Triggered Integral Sliding Mode Control for Nonlinear Networked Cascade Control Systems With Uncertain Delay

ABSTRACTThis article investigates the problem of event‐triggered integral sliding mode control (ISMC) for a class of nonlinear networked cascade control systems (NCCSs). Due to the limited communication bandwidth between network nodes, uncertain delay can occur during transmission. This may result in a deterioration of the capabilities of NCCS and system instability in certain instances. Thus, an event‐triggered mechanism (ETM) and ISMC are introduced into the system, and a new model is constructed to increase the network bandwidth and reduce the effect of nonlinear perturbation. After that, the design of two controllers and ETM is accomplished through the use of the Lyapunov generalized method and linear matrix inequality (LMI) techniques. Finally, a simulation example of a power plant model is given to verify the effectiveness of the method. The results show that, for the first time, the event‐triggered ISMC is applied to NCCSs, which greatly saves the network bandwidth resources. The states of the system can reach the sliding mode surface (SMS) in finite time and remain stabilized there afterward, which ensures the stable operation of the system.

Generalized black hole entropy is von Neumann entropy

It has been argued that, while the individual terms in the generalized entropy, Sgen=A/4GN+Sext, are ill-defined in the semiclassical limit, their sum is well-defined if one takes into account perturbative quantum gravitational effects. The first term diverges as GN→0, and the second diverges due to the infinite entanglement across the horizon which is characteristic of type III von Neumann algebras. It was recently shown that the von Neumann algebra of observables “gravitationally dressed” to the mass of a Schwarzschild-AdS black hole or the energy of an observer in de Sitter spacetime admit a well-defined trace. The algebras are type II∞ (which does not admit a maximum entropy state) and type II1 (which admits a maximum entropy state) respectively, and the von Neumann entropy of “semiclassical” states was found to be (up to an additive constant) the generalized entropy. However, these arguments rely on the existence of a stationary “equilibrium (KMS) state” and do not apply to, for example, black holes formed from gravitational collapse, Kerr black holes, or black holes in asymptotically de Sitter spacetime. These spacetimes are stationary but not in thermal equilibrium. In this paper, we present a general framework for obtaining the algebra of “gravitationally dressed” observables for a linear, Klein-Gordon field on any spacetime with a (bifurcate) Killing horizon. We prove, assuming the existence of a stationary state—which is not necessarily KMS—and suitable asymptotic decay of solutions, a “structure theorem” that the algebra of “gravitationally dressed” observables always contains a type II factor of observables “localized” on the horizon. These assumptions have been rigorously proven in most cases of interest in this paper. Applying our general framework to the algebra of observables in the exterior of an asymptotically flat Kerr black hole where the fields are dressed to the black hole mass and angular momentum we find that the algebra is the product of a type II∞ algebra on the horizon and a type I∞ algebra at past null infinity. The full algebra is type II∞, and the von Neumann entropy of semiclassical states is the generalized entropy. In the case of Schwarzschild-de Sitter, despite the fact that we must introduce an observer, the algebra of observables dressed to the perturbed areas of the black hole and cosmological horizons is the product of type II∞ algebras on each horizon. The entropy of semiclassical states is given by the sum of the areas of the two horizons as well as the entropy of quantum fields in between the horizons. Our results suggest that in all cases where there exists another “boundary structure” (e.g., an asymptotic boundary or another Killing horizon) the algebra of observables is type II∞ and in the absence of such structures (e.g. de Sitter spacetime) the algebra is type II1. Published by the American Physical Society 2025

The robustness of inferred envelope and core rotation rates of red giant stars from asteroseismology

Context. Rotation is an important phenomenon influencing stellar structure and evolution, however, it has not been adequately modelled thus far. Therefore, accurate estimates of internal rotation rates are valuable for constraining stellar evolution models. Aims. We aim to assess the accuracy of asteroseismic estimates of internal rotation rates and how they depend on the fundamental stellar parameters. Methods. We applied the recently developed extended-multiplicative optimally localised averages (eMOLA) inversion method, to infer localised estimates of internal rotation rates of synthetic observations of red giants. We searched for suitable reference stellar models, following a grid-based approach, and we assessed the robustness of the resulting inferences with respect to the choice of reference model. Results. We find that matching the mixed-mode pattern between the observation and the reference model is an important criterion for selecting suitable reference models. We propose (i) selecting a set of reference models based on the correlation between the observed rotational splittings and the mode-trapping parameter; (ii) computing the rotation rates for all these models; and (iii) using the average value obtained across the whole set as the estimate of the internal rotation rates. We find that the effect of a near surface perturbation in the synthetic observations on the rotation rates estimated based on the correlation between the observed rotational splittings and the mode-trapping parameter is negligible. Conclusions. We conclude that when using an ensemble of reference models that are selected by matching the mixed-mode pattern, the input rotation rates can be recovered across a range of fundamental stellar parameters such as mass, mixing-length parameter, and composition. Further, red giant rotation rates determined in this way are also independent of any near-surface perturbation of the stellar structure.

Assessing the impact of conformational perturbants on folding and aggregation pathways of a β-barrel fold.

Here we explore the interplay between physical and chemical perturbants to unravel links among native folding, amorphous and ordered aggregation scenarios in IFABP (rat intestinal fatty acid binding protein). This small beta-barrel protein undergoes amyloid-like aggregation above 15% v/v trifluoroethanol. Our aim was to address the influence of sub-aggregating TFE concentrations on the unfolding transitions of IFABP. The urea-induced unfolding process can bona fide be considered a two-state transition where no aggregation takes place. On the other hand, with GdmCl, the appearance of amyloid-like aggregation becomes evident upon TFE challenge. Temperature-induced denaturation profiles show that both additives, TFE and GdmCl decrease protein stability. Whereas amorphous aggregation occurs upon heating in the presence of TFE, no aggregation takes place with GdmCl. Conversely, when both additives are present, amyloid-like aggregation prevails. The explanation for the choice of amorphous or amyloid-like pathways must reconcile the effects of perturbants on both the protein and solvent structures. Key points include the TFE-promoted desolvation of the polypeptide, a process further enhanced by heat. Although GdmCl might prevent amorphous thermal aggregation by solubilizing non-native states, this effect could also favor amyloid aggregation. In addition, the electrolyte-induced segregation of TFE at high enough GdmCl concentration might contribute to the development and/or stabilization of TFE clusters that could act as nucleation-inducing interfaces, thus leading to the observed amyloid aggregation outcome.

Effects of temperature on flame structures and local extinctions of swirl spray flames

The effects of air inlet temperature on the flame structures and the local extinctions of n-decane swirl spray flames at constant air flow velocity were clarified by using the simultaneous planar laser induced fluorescence measurements of OH and CH2O. Results show that the blowoff limit decreases 48% as the temperature increases from 298 to 473 K. The OH and the [CH2O] × [OH] overlap are mainly distributed near the shear layer, while a small amount of formaldehyde is also observed in the outer recirculation zone (ORZ), corresponding to the low-temperature reactions. The formaldehyde intensity in the ORZ varies non-monotonically with the temperature. The non-monotonic temperature dependence of the formaldehyde intensity is governed by the competition of the droplet evaporation rate and the initial droplet size. The local extinctions of swirl spray flames can be identified by the formation of holes or breaks in the OH branches together with the accumulation of formaldehyde. It suggests that the combination of OH and CH2O is a good indicator to predict the local extinctions. The probability of the local extinctions decreases gradually with the temperature. The locations of the local extinction move downstream from 333 to 423 K; however, the local extinctions occur frequently near the flame root at 473 K. It reveals that the local extinctions near the flame root are mainly associated with the cooling effect and the perturbation effect of the flame–droplet interactions at low temperature and at high temperature, respectively.

Effects of wall perturbations on the stabilized FEM solution of steady MHD flow in a duct

In this study, the effects of curved boundary perturbations on the solution of steady magnetohydrodynamic (MHD) duct flow are investigated. Hartmann (upper and bottom) walls are perturbly curved and perfectly conducting while the side walls are insulated and plane. The velocity of the flow and induced magnetic field are obtained numerically by solving the steady MHD flow coupled equations using the finite element method (FEM with Streamline Upwind Petrov Galerkin (SUPG)) stabilization to inhibit instabilities in the flow. The results are obtained for Hartmann number ($Ha$) values up to $500$, for several definitions of the curved upper and bottom walls, and for several values of perturbation parameters of the curved walls ($0 \le \epsilon_u , \epsilon_b \le 0.3$). The velocity and the induced magnetic field sensitivity to the curved wall shapes are visualized in terms of equivelocity and current lines. It is found that the flow and the induced magnetic field are affected by the curved boundary shapes especially near those boundaries and also, to some extent, in the whole duct. It is also observed that increasing the Hartman number pushes the flow near the upper boundary even if both upper and bottom walls are perturbed since the external magnetic field applies vertically. The increase in the perturbation parameter of the curved upper boundary forces the flow to move through this wall and the induced magnetic field reaches its maximum value near the maximum points of the perturbed curve. Further, an increase in ${\rm Ha}$ delays the effect of the curved boundaries and gives rise to flattened flow with side layers and stagnant fluid at the central part of the duct overwhelming the effects of curved boundaries.

Efficacy of two novel antifungal lipopeptides, AF4 and AF5 of bacillomycin D family in murine models of invasive candidiasis, cryptococcosis, and aspergillosis.

Invasive fungal diseases are an important public health concern due to an increase in the at-risk population and high mortality associated with these infections. Managing invasive fungal infections poses a significant challenge given the limited antifungal options and the emergence of resistance in key fungal pathogens. Through a comprehensive approach, we evaluated the in vitro antifungal activity and the in vivo efficacy of two novel lipopeptides, AF4 and AF5 in murine models of disseminated candidiasis, cryptococcosis, and aspergillosis. Flow cytometry analysis with propidium iodide showed a dose-dependent increase in the permeability and disruption of fungal cell membranes, underscoring the membrane perturbing effects of AF4 and AF5. These observations were further substantiated by SEM analyses that showed yeast cell and hyphal deformation and leakage of cellular contents. Our in vivo investigations utilizing two doses (5 and 10 mg/kg bodyweight) of each lipopeptide and its comparison with standard antifungal therapies showed lipopeptides significantly improved the odds of mice survival in invasive candidiasis and cryptococcosis models, with a reduction in organ fungal burden by 2 to 3-log10 order. Additionally, in the disseminated aspergillosis model, treatment with 10 mg/kg of AF4 significantly improved median survival from 4 to 10 days while achieving a notable 1-log10 order reduction in organ fungal burden. Overall, our study underscores the potent and broad-spectrum antifungal activity of lipopeptides in mouse infection models, hinting at their promising therapeutic potential in invasive fungal disease.

Enabling Electric Field Model of Microscopically Realistic Brain.

Modeling brain stimulation at the microscopic scale may reveal new paradigms for various stimulation modalities. We present the largest map to date of extracellular electric field distributions within a layer L2/L3 mouse primary visual cortex brain sample. This was enabled by the automated analysis of serial section electron microscopy images with improved handling of image defects, covering a volume of 250 × 140 × 90 μm³. The map was obtained by applying a uniform brain stimulation electric field at three different polarizations and accurately computing microscopic field perturbations using the boundary element fast multipole method. We used the map to identify the effect of microscopic field perturbations on the activation thresholds of individual neurons. Previous relevant studies modeled a macroscopically homogeneous cortical volume. Our result shows that the microscopic field perturbations - an 'electric field spatial noise' with a mean value of zero - only modestly influence the macroscopically predicted stimulation field strengths necessary for neuronal activation. The thresholds do not change by more than 10% on average. Under the stated limitations and assumptions of our method, this result essentially justifies the conventional theory of "invisible" neurons embedded in a macroscopic brain model for transcranial magnetic and transcranial electrical stimulation. However, our result is solely sample-specific and is only relevant to this relatively small sample with 396 neurons. It largely neglects the effect of the microcapillary network. Furthermore, we only considered the uniform impressed field and a single-pulse stimulation time course.

Study on the parameters of steel plate reinforcement rib-deck crack considering local stress disturbances

Local reinforcement will change the local stiffness distribution of the component, causing perturbation effects on the local stress of the fatigue detail. Only considering the reinforcement effect may lead to excessive strengthening and induce new fatigue-prone points. For the fatigue detail of the rib-deck weld, steel plate reinforcement test and numerical simulations were conducted. The stress changes of the deck weld toe and weld root before and after reinforcement were analyzed. The influence of parameters such as steel plate length, thickness, and width on the reinforcement effect of the weld toe crack and local stress disturbance was discussed, and reasonable parameters were recommended. The results show that after the cracking of the weld toe, the stress concentration locations at the weld toe and weld root of the deck shift from the center of the specimen to the crack tip. Steel plate reinforcement can effectively restrain the crack propagation, but can lead to an increase in the stress at the deck weld root within the reinforced area. A good reinforcement effect can be achieved while the steel plate covers the crack, and further increasing the steel plate length has limited improvement on the reinforcement effect but reduces the adverse effect of steel plate reinforcement on the stress of the deck weld root. Increasing the steel plate width will increase the adverse effect of steel plate reinforcement on the deck weld root stress, and it is recommended to use steel plates with a length greater than 120 mm and a length-to-width ratio greater than 4 for reinforcement. Increasing the width of the steel plate has a relatively small effect on the reinforcement effect and the stress at the deck weld root, and steel plates with the same thickness as the deck are recommended.

CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.

Pooled genetic screening with CRISPR-Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust results. However, resolution is limited in complex, heterogeneous models, such as organoids or tumors transplanted into mice, because achieving sufficient representation requires impractical scaling. This is due to bottleneck effects and biological heterogeneity of cell populations. Here we introduce CRISPR-StAR, a screening method that uses internal controls generated by activating sgRNAs in only half the progeny of each cell subsequent to re-expansion of the cell clone. Our method overcomes both intrinsic and extrinsic heterogeneity as well as genetic drift in bottlenecks by generating clonal, single-cell-derived intrinsic controls. We use CRISPR-StAR to identify in-vivo-specific genetic dependencies in a genome-wide screen in mouse melanoma. Benchmarking against conventional screening demonstrates the improved data quality provided by this technology.

ON THE STABILITY BY THE NONLINEAR NON-STATIONARY HYBRID APPROXIMATION

The paper investigates the effect of non-stationary perturbations on the stability of nonlinear nonautonomous systems with switching and impulsive effects. Sufficient conditions have been obtained to guarantee the asymptotic stability of a given equilibrium position of the initial system, and restrictions have been established under which the asymptotic stability is preserved under perturbations acting on the system. Note that the non-stationarities present both in the system itself and in perturbations can be described by unbounded functions with respect to time, as well as functions arbitrarily close to zero. It is assumed that the basic system is homogeneous in terms of the state vector. To find the required results, the second Lyapunov method is used in combination with the theory of differential inequalities.