Simple Folding Research Articles

Dual-channel foldable microfluidic paper-based parallel enzymatic reaction systems for simultaneous visual colorimetric detecting acetylcholinesterase and α-glucosidase together with screening inhibitors

On-site multi-enzymes detection and inhibitors screening are still challenging and particularly urgent. Here, dual-channel foldable microfluidic paper (μPAD)-based parallel enzymatic reaction systems were fabricated for simultaneous visual colorimetric detecting acetylcholinesterase (AChE) and α-glucosidase (α-Glu) together with screening inhibitors. μPAD composing of two layers with dual channels was designed and prepared facilely by a permanent marker. AChE and α-Glu catalyze pre-loaded substrates into products (thiocholine (TCh), ascorbic acid (AA)) on the 1st layer. Parallelly, oxidase-like MnO2 nanosheets oxidize pre-dropped colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB) on the 2nd layer. After simple folding μPAD, TCh and AA can reduce oxTMB to TMB, resulting in color fading. Obviously, bioenzyme and nanozyme reactions under different pH can simultaneously occur on the μPAD. Furthermore, colorimetric results can be easily captured and on-site quantitatively analyzed by smartphone. As a result, a convenient, efficient, sensitive, and specific platform has been constructed for simultaneous detecting AChE and α-Glu in human serum samples (recoveries, 92.1–105.0%; relative standard deviations, < 3.6%), and screening inhibitors from synthesized compounds and natural products. The developed platform provides constructive insights for exploitation of visual detecting strategies for simultaneous sensing muti-targets for point-of-care testing of disease and development of drugs.

Mapping the semi-nested community structure of 3D chromosome contact networks.

Mammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes' 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome's actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that cross-scale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding.

Non-coaxial deformation of foreland basement involved in a fold-and-thrust belt: a strain partitioning approach to the Eastern Variscan orogen

The general SW–NE course of the Variscan orogen in Europe is abruptly bent to the N–S course at its eastern margin, where an oblique convergence occurred. The main suture in this part of the Variscan orogenic belt is called the Moldanubian Thrust, characterized by a dominant dextral strike-slip kinematics and a minor thrust component. The deep level of erosion and the good exposure of this structure allowed us to study the mechanisms of oblique convergence and the incorporation of the foreland basement into the orogenic belt. The combination of small-scale structures with the anisotropy of magnetic susceptibility studies allowed the recognition of two deformations in the studied rocks: dextral simple shearing and drag folding. Due to oblique convergence, the deformations induced by this mechanism were non-coaxial; therefore, their contributions can be easily distinguished. Finally, an overturned, almost recumbent large-scale synformal fold structure in the footwall and an antiformal structure in the hanging wall of the Moldanubian Thrust were formed. These two folds can be interpreted as structures formed by dragging along the Moldanubian Thrust. The previously described sinistral simple shearing in the upper limb of the synform resulted from the original dextral strike-slip shearing, which was overturned during progressive deformation.

A Tunable Zig-Zag Reflective Elastic Metasurface

In this paper, inspired by origami structures, we offer a very simple tuning method to overcome the limitations of general elastic metasurfaces, where only a certain functionality at a certain frequency range can be achieved, by designing a reflective metasurface based on foldable/deployable zig-zag structures. By utilizing peg/screw connections, the folding angles of the zig-zag structures can be easily tuned while also being fixable. By tuning the folding angle, the subunit of the zig-zag metasurface can cover a 2π phase shift span and the phase shift can be tuned continuously, and almost linearly, with respect to the folding angle. With a simple folding motion, the tunable reflective metasurface can steer reflected flexural waves in different directions and focus-reflected flexural waves with different focal distances. In addition to demonstrating tunable performance, the mechanism that associates the changing speed of the phase shift is explained. The proposed tunable zig-zag elastic metasurface provides a new way to design reconfigurable metamaterials/metasurfaces.

"Collar-like" neocommissure in mitral valve repair for extensive commissural prolapse.

ObjectivesMitral valve repair for extensive commissural prolapse is complex; several methods have been reported with variable results. To restore the leaflet area, we introduced an innovative and effective method rather than a simple folding technique through reconstructing a neocommissure with a “collar-like” plasty technique.MethodsFrom 2016 to 2021, 62 patients with mitral valve extensive commissural prolapse that received the “collar-like” plasty technique were included.ResultsThe mean age was 51.7 ± 13.8 years, and 38 (61%) were female. Postplasty transesophageal echocardiography showed the mean transvalvular pressure gradients were 3.8 ± 1.2 mm Hg, end diastolic peak flow velocity was 1.1 ± 0.3 m/s, and coaptation height was 7.9 ± 1.1 mm. During the follow-up period of 3 to 6 months, no deaths or cardiovascular-/valvular plasty-related adverse events occurred. All patients regained their heart function and returned to normal physical activities.ConclusionsThe “collar-like” plasty technique can be safely performed for patients with extensive commissural prolapse. Echocardiography revealed that the technique can restore the leaflet area of low transvalvular pressure and flow velocity.

Insights into the subsurface structure of wrinkle ridges on Mars

Wrinkle ridges are important landforms on Mars and other planetary bodies and result from horizontal tectonic shortening. This study provides insights into the subsurface of selected wrinkle ridge sites, based on exposures provided by steep escarpments and crater slopes that crosscut wrinkle ridges. We mapped the complex fold and fault patterns and measured fault dips, where faults appear planar. The fault pattern underneath wrinkle ridges is diverse and is dominated by reverse faults and thrusts. The predominance of one fault system leads to morphological asymmetries of many wrinkle ridges. The upper tip of the dominant thrust fault is commonly situated beneath the steeper wrinkle ridge slope and may outcrop at its base. Polarity changes of wrinkle ridges along strike go along with a change of the dominant thrust direction. Symmetric wrinkle ridges are formed when a conjugate system of thrusts exists in the subsurface. Several wrinkle ridges display a main thrust fault whose dip angle bends over to a shallower dip at depth. The measurements of average dip for primary thrust and backthrust faults are 37° ± 2° and 28 ± 2°, respectively. In general, most of the examined wrinkle ridges are characterized by a multitude of subsidiary and backthrust faults. With the limitation that the uppermost 500-1000 m of the wrinkle ridges subsurface are accessible in this study and despite the large morphological and structural variability of wrinkle ridges, the kinematics of fault-propagation folds models seem to show a large match to our observations and measurements. Likewise, continuum mechanics models show a good fit to the obtained structural data. Fault-bend fold models and simple buckle folding models seem less compatible with observations.

Small-scale, storable paper biobatteries activated via human bodily fluids

Herein, a fully paper-based biobattery composed of four microbial fuel cell (MFC) units is evaluated, one that can be prepared in advance, stored, and quickly activated with virtually any available fluid. The biobattery uniquely utilizes Bacillus subtilis endospores as the storable anodic biocatalyst; the dormant, robust nature of B. subtilis endospores should allow for device preinoculation with spores followed by prolonged storage of the fully fabricated paper battery until needed. A germinant paper layer strategically fabricated above the spore-loaded anode layer contains all of the necessary chemical germinants and nutrient components required for the endospores to begin germination, exit dormancy, and return to fully metabolic vegetative bacterial cells that can generate electrical energy. This mechanism allows for the battery to be simply initiated via a wide range of available liquids. Bioelectricity generation of the battery is successfully demonstrated after introduction of a variety of artificial bodily fluids, including saliva, sweat, and urine, along with tap water. Since the biobattery has the capability of serially linking all 4 of its MFCs through simple dynamic folding, the device’s total power output can be greatly enhanced; a single biobattery is able to achieve 0.56 V and 2.4 μW, which is beyond the ratings required for their intended application in single-use, disposable sensors. Therefore, this concept of integrating 4 spore-based MFCs into a single biobattery device with a built-in germinant layer offers a potential solution for stable, long-term storable power sources, displaying feasibility for integration with low power, disposable sensor applications.

Origami-inspired folding assembly of dielectric elastomers for programmable soft robots

Origami has become an optimal methodological choice for creating complex three-dimensional (3D) structures and soft robots. The simple and low-cost origami-inspired folding assembly provides a new method for developing 3D soft robots, which is ideal for future intelligent robotic systems. Here, we present a series of materials, structural designs, and fabrication methods for developing independent, electrically controlled origami 3D soft robots for walking and soft manipulators. The 3D soft robots are based on soft actuators, which are multilayer structures with a dielectric elastomer (DE) film as the deformation layer and a laser-cut PET film as the supporting flexible frame. The triangular and rectangular design of the soft actuators allows them to be easily assembled into crawling soft robots and pyramidal- and square-shaped 3D structures. The crawling robot exhibits very stable crawling behaviors and can carry loads while walking. Inspired by origami folding, the pyramidal and square-shaped 3D soft robots exhibit programmable out-of-plane deformations and easy switching between two-dimensional (2D) and 3D structures. The electrically controllable origami deformation allows the 3D soft robots to be used as soft manipulators for grasping and precisely locking 3D objects. This work proves that origami-inspired fold-based assembly of DE actuators is a good reference for the development of soft actuators and future intelligent multifunctional soft robots.

Turning machines: a simple algorithmic model for molecular robotics

Molecular robotics is challenging, so it seems best to keep it simple. We consider an abstract molecular robotics model based on simple folding instructions that execute asynchronously. Turning Machines are a simple 1D to 2D folding model, also easily generalisable to 2D to 3D folding. A Turning Machine starts out as a line of connected monomers in the discrete plane, each with an associated turning number. A monomer turns relative to its neighbours, executing a unit-distance translation that drags other monomers along with it, and through collective motion the initial set of monomers eventually folds into a programmed shape. We provide a suite of tools for reasoning about Turning Machines by fully characterising their ability to execute line rotations: executing an almost-full line rotation of 5π/3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5\\pi /3$$\\end{document} radians is possible, yet a full 2π\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2\\pi$$\\end{document} rotation is impossible. Furthermore, line rotations up to 5π/3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5\\pi /3$$\\end{document} are executed efficiently, in O(logn)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$O(\\log n)$$\\end{document} expected time in our continuous time Markov chain time model. We then show that such line-rotations represent a fundamental primitive in the model, by using them to efficiently and asynchronously fold shapes. In particular, arbitrarily large zig-zag-rastered squares and zig-zag paths are foldable, as are y-monotone shapes albeit with error (bounded by perimeter length). Finally, we give shapes that despite having paths that traverse all their points, are in fact impossible to fold, as well as techniques for folding certain classes of (scaled) shapes without error. Our approach relies on careful geometric-based analyses of the feats possible and impossible by a very simple robotic system, and pushes conceptional hardness towards mathematical analysis and away from molecular implementation.

Folded Propeller Chiral Structures Exclusively Adaptive to Chloroform.

Intramolecular folding is a strategy to construct aryl chiral compounds with applications in chiroptical materials and asymmetrical catalysts. However, beyond polarity the role of solvent in controlling the folded chirality is ambiguous. Here, we report a simple folding protocol to build chiral benzimidazole skeleton with propeller chirality, which could be adaptive to chloroform (CHCl3) with high selectivity. Benzimidazole conjugated with diamino acid arms underwent folding driven by hydrogen bonds, exhibiting propeller chirality of which handedness could be tuned by the absolute chirality of amino acids. Reversible unfolding/folding behavior was realized by heating/cooling process, giving rise to the thermomediated chiroptical switch. Among up to 32 common solvents, chloroform exclusively inverted the propeller chirality. The geometry and hydrogen bonding sites of chloroform allow rearrangement of diamino acid arms into an opposite packing propensity. The chloroform behaves as an invasive linker between diamino acid arms to replace the pristine hydrogen bonds. This work reports the fabrication of chiral aryl compounds by simple folding, which shows the adaptiveness to the chloroform. It demonstrates that not only polarity but also the active participation of solvent could change the chirality and optical activities of small folded molecules.

Efficient segment folding is hard

We introduce a computational origami problem which we call the segment folding problem: given a set of n line-segments in the plane the aim is to make creases along all segments in the minimum number of folding steps. Note that a folding might alter the relative position between the segments, and a segment could split into two. We show that it is NP-hard to determine whether n line segments can be folded in n simple folding operations.

A Comparison of Different Folding Models in Variations of the Map Folding Problem

In this paper, we compare the performance of three different folding models when they are applied to three different map folding settings. Precisely, the three folding models include the simple folding model, the simple folding–unfolding model, and the general folding model. The different map folding settings are discussed by comparing different folded states, i.e., different overlapping orders on the set of the squares of 1 × n maps, the squares of m × n maps, and the squares lying on the boundary of m × n maps. These folding models are abstracts of manual works and robotics. We clarify the relationship between their reachable final folded states under different settings and give proof of all the inclusion relationships between every two of these sets. In addition, there are nine distinct problems with the three folding models applied to three folding settings. We give the optimal linear time solutions to all the unsolved ones: the valid total overlapping order problems of 1 × n maps, m × n maps, as well as the valid boundary overlapping order problems of m × n maps with the three different folding models. Our work gives the conclusion of the research field where the folding models and the overlapping orders of map folding are concerned.

3D origami paper-based ratiometric fluorescent microfluidic device for visual point-of-care detection of alkaline phosphatase and butyrylcholinesterase

On-site multiplex enzyme detection is crucial for diagnosis, therapeutics and prognostic. To date, it is still a daunting challenge to develop portable, low-cost, and efficient multi-enzyme detection methods. Herein, a novel sample-in-result-out platform integrating ratiometric fluorescent assays with 3D origami microfluidic paper-based device (μPAD) was developed for simultaneous visual point-of-care testing (POCT) of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Cascade catalytic reaction with the same two fluorescent signal indicators was rationally designed to ratiometric fluorescent detection of ALP and BChE: substrate of ALP (pyrophosphate) and product of BChE (thiocholine) can strongly complex with Cu2+, Cu2+ oxidizes o-phenylenediamine to fluorescent 2,3-diaminophenazine (oxOPD) (emission, 565 nm), oxOPD quenches the fluorescence of carbon dots (CDs, emission at 445 nm) via inner filter effect, thus oxOPD/CDs values are relevant to ALP and BChE activities. Then 3D origami μPAD composing of four layers and two parallel channels was fabricated and simply prepared by one-step plotting with black oil-based marker and specific metal molds. After simple folding and unfolding neighboring layers to sequentially initiate reactions of pre-loaded reagents, fluorescent images on the detection zone can be captured by smartphone and analyzed by red-green-blue software for quantitative analysis. Under optimal conditions, the proposed platform was successfully performed to detect ALP and BChE with activity difference at 3 orders of magnitude in human serum samples without any pretreatment procedures. Excellent selectivity, good precision, favorable linear range, and high accuracy were exhibited. Importantly, the platform opens a promising horizon for high-throughput POCT of multiplex biomarkers.

Study on effect of offset defect on mechanical property of honeycomb structures

Honeycomb is widely used because of its excellent energy absorption characteristics during compression. However, offset defects in the manufacturing process are inevitable and affect the energy absorption characteristics. In order to study the effect of offset defect, the finite element model was established firstly. The verified finite element model was used to simulate the honeycomb structure under different offsets. The simulation shows that with the increase of the offset λ, the deformation mode of the honeycomb can be divided into three stages and the platform strength increased first and then decreased, and the decrease was obviously greater than the increase. Then the theoretical calculation formula of platform strength of the honeycomb under offset defect was obtained by simple folding theory. The results show that for commonly used honeycomb specifications, when λ = 0.4, the platform strength increases the most, which is 7.99%, and when λ = 1.0, the platform strength decreases the most, which is 18.03%. The theoretical results are similar to the simulation results. For Y-shaped element, the errors are 2.13% and 2.04% at λ = 0.4 and 1.0 respectively, for whole honeycomb, the errors are 0.29% and 4.82% at λ = 0.4 and 1.0 respectively. Therefore, the platform strength of honeycomb can be improved by increasing the offset appropriately.

The Effect of Marketing Strategies on the Tourism Development of Archaeological Sites

The current study aims to test the impact of marketing strategies on tourism development, as well as to identify the nature of the practice and interest of the Antiquities and Heritage Authority and its affiliated sites, as the importance of the study stems from the limitations of previous studies that tried to identify and know the type of relationship between research variables (marketing strategies, tourism development) Add to this the researcher's attempt to address a realistic problem that mainly affects the tasks and work of the Antiquities and Heritage Authority at the near and far level, so the study adopted the intentional stratified sampling method, and distributed (100) questionnaires as a main tool for data collection, to (director, assistant director, head of department, responsible (Division, employee) at the headquarters of the Commission, and the number of recovered persons was (86), of which (79) were a questionnaire suitable for statistical analysis. Analytical, historical method, and statistical methods were used to analyze the practical aspect (weighted mean, standard deviation, coefficient of variation, relative importance, T-test, simple correlation coefficient Pearson, regression etc. The simple and multiple folding), and the descriptive and inferential statistical analysis has concluded the most prominent result, by employing the Antiquities and Heritage Authority for marketing strategies in tourism development, especially when it uses the market-oriented strategy, focusing on the main customers, and organizational efficiency in promoting the tourism development of the Authority.

Origami-Structured Actuating Modules for Upper Limb Support

Soft pneumatic actuators (SPAs) based on inherently compliant materials have been developed by integrating with a fabric, a fiber reinforcement, or applying origami patterns. However, the fabric and fiber-reinforced SPAs are limited by the relatively large volumes of air needed to achieve the desired motions, and conventional `origami-structured' SPAs based on simple paper folding may not be durable and provide limited force. In this letter, an origami-structured actuating module fabricated by embedding a rigid origami structure in a fabric, which is applicable to any origami patterns including Yoshimura, Waterbomb, and so on, was proposed to improve durability and supporting force. Specially, the Yoshimura pattern-based origami-structured actuating module was analytically modeled to determine the design parameters of the actuating module so that it can provide enough supporting force and range of motion of the upper limb. A wearable system with the optimized origami-structured actuating module, which is durable, adaptable, and capable of supporting the upper limb motion, was developed to assist the upper limb without interfering natural movements.

The Endocranial Cast of Indohyus (Artiodactyla, Raoellidae): The Origin of the Cetacean Brain

We present the first description of the endocranial cast of the small raoellid artiodactyl Indohyus indirae. Raoellidae are sister group to Cetacea and the new morphological observations allow for outlining some of the early steps of the evolutionary history of the cetacean brain. The combination of primitive artiodactyl features and typical cetacean characters is unique about the Indohyus endocast. The fact that it presents the symplesiomorphic brain pattern observed in earliest Artiodactyla indicates that the cetacean brain derives from a very simple, plesiomorphic brain, with simple neocortical folding pattern, widely exposed midbrain, and concurrent small neocortex expansion. On the other hand, the Indohyus endocast shows characters that also occur in early cetaceans. These include modifications of the olfactory tract with narrow, elongated olfactory bulbs and peduncles, accompanied by a posterior location of the braincase in the cranium. The derived endocranial cast features of Indohyus mainly reflect changes in cranial architecture and these are most probably associated with modifications of the masticatory apparatus and a shift in diet. Indohyus meninges were very thin as in most terrestrial artiodactyls and it had no extensive rostral or lateral retia mirabilia. It however shows a branching pattern of ramification of intraosseous blood sinuses above the cerebellum that might represent the initial development of the caudal venous rete mirabile that would have colonized the endocranial cavity later on, in early archaeocetes.

Performance investigation on the novel anti-leakage and easy-to-manufacture trisection helical baffle electric heaters

The difficult manufacturing of helical baffles hinders the widespread application of the enhancement technology and the shortcut leakage between adjacent baffles impairs the enhancement effects. To solve these two issues, the promising anti-leakage and easy-to-manufacture helical baffles with small inclined angle and folded structure are proposed, which can be produced by 2D laser cutting and simple mechanical folding. The influence of different helical baffle configurations, including three normal helical schemes, three axial separation helical schemes, three novel folded axial separation helical baffle schemes and a segmental scheme on the performance of electric heaters are numerically investigated. The equivalent angles of helical schemes adopted in this work are 15°, 20° and 25°, and the inclined angle of helical baffles under axial separation connection style is 10°. Compared with the corresponding axial separation scheme without folding, the leakage can be significantly decreased, the heat transfer coefficients h and the comprehensive indices h⋅Δp−1/3 of FH15(10)°, FH20(10)° and FH25(10)° are increased by 6.5%/2.3%, 12.2%/7.3% and 20.4%/13.0%, and the averaged tube wall temperatures Tw are decreased by 12.5 K, 25.4 K and 54.7 K, respectively. This research can provide feasibility for the extended application of helical baffles in electric heaters or heat exchangers.

The Folding Pathway of 6aJL2.

One-third of the reported cases of light chain amyloidosis are related to the germ line λ6 family; remarkably, healthy individuals express this type of protein in just 2% of the peripheral blood and bone marrow B-cells. The appearance of the disease has been related to the inherent properties of this protein family. A recombinant representative model for λ6 proteins called 6aJL2 containing the amino acid sequence encoded by the 6a and JL2 germ line genes was previously designed and synthesized to study the properties of this family. Previous work on 6aJL2 suggested a simple two-state folding model at 25 °C; no intermediate could be identified either by kinetics or by fluorescence and circular dichroism equilibrium studies, although the presence of an intermediate that is populated at ∼2.4 M urea was suggested by size exclusion chromatography. In this study we employed classic equilibrium and kinetic experiments and analysis to elucidate the detailed folding mechanism of this protein. We identify species that are kinetically accessible and/or are populated at equilibrium. We describe the presence of intermediate and native-like species and propose a five-species folding mechanism at 25 °C at short incubation times, similar to and consistent with those observed in other proteins of this fold. The formation of intermediates in the mechanism of 6aJL2 is faster than that proposed for a Vκ light chain, which could be an important distinction in the amyloidogenic potential of both germ lines.

A new early warning indicator of abrupt climate change based on the changing normalized dynamic range

AbstractAn abrupt change will occur when the system is forced to across a critical threshold. This study presents a novel early warning indicator—the changing normalized dynamic range. We use a one‐variable climate model and three simple folding models to test the performance of the new early warning indicator. The results show that the present indicator exhibits a statistically significant increase or decrease in all of tests at a significance level of α = .05 before a dynamical system with a folding bifurcation approaches a tipping point. Comparing the well‐known autocorrelation coefficient with the normalized dynamic range, it is found that autocorrelation coefficient performs well in most of tests, which shows an almost monotonous increasing or decreasing trend for an upcoming abrupt change. However, autocorrelation coefficient exhibits a diametrically opposite trend for a noise‐induced abrupt change in a two‐dimensional vegetable model. The kurtosis coefficient can perform well in most of the tests used in this study, however, fails to give an early warning in a particular case. Moreover, the magnitude of change of the autocorrelation and kurtosis is much smaller than that of the normalized dynamic range before the four folding models approach its tipping point. Therefore, the performance of the new indicator for warning an abrupt change in advance is better than that of the autocorrelation coefficient as well as kurtosis coefficient, which can make up for the deficiency of the kurtosis coefficient and autocorrelation coefficient to some extent.