This study concerns optimizing the eigenfrequencies of circular cylindrical laminates. The stiffness properties are described by lamination parameters to avoid potential solution dependency on the initial assumptions of the laminate configurations. In the lamination parameter plane, novel response contours are obtained for the first and second natural frequencies as well as their difference. The influence of cylinder length, radius, thickness, and boundary conditions on the responses is investigated. The lamination parameters yielding the maximum response values are determined, and the first two mode shapes are shown for the optimum points. The results demonstrate that the maximum fundamental frequency points of the laminated cylinders mostly lie at the inner lamination parameter domain, unlike the singly curved composite panels. In addition, the second eigenfrequency shows a nonconvex response surface containing multiple local maxima for several cases. Moreover, the frequency difference contours appear as highly irregular, which is unconventional for free vibration responses. Laminated composite materials are extensively used in the construction, aerospace, automotive, and marine industries. In addition to their high stiffness-to-weight ratio, such materials offer the possibility of tailoring the stiffness properties for specific applications. Hence, the design of engineering structures made of laminated composites has been widely addressed in the literature.One particular group of laminated structures comprises cylinders, which are commonly utilized as the shells of aircraft and satellites. These structures are frequently designed to provide optimal natural frequencies to prevent resonances under expected dynamic operating conditions. In this context, the fundamental natural frequency has been prevalently selected as the design objective to be maximized. For instance, Nshanian and Pappas  maximizeAnother widespread approach is the maximization of the difference between the adjacent eigenfrequencies of the structure ,9,10. ThIn laminate stacking sequence optimization, the optimal designs may depend on the initial assumptions regarding the number of layers and layer thicknesses. As a remedy, lamination parameters have been introduced to describe the overall stiffness properties with intermediate variables . This teThis study addresses the eigenfrequency optimization of circular composite cylinders. The stiffness properties are described using lamination parameters, which are optimized as the design variables. The first  eigenfrequency or the separation between the first and second eigenfrequencies are maximized as the objective functions. The response contours for the first and second natural frequencies of the composite cylinders as well as their difference are obtained in the lamination parameter plane for the first time. In many cases, the maximum fundamental frequency points occurred at the interior region of the lamination parameter domain, thus requiring layer angles of multiple absolute values in the stacking sequence retrieval. This finding demonstrates that the stiffness tailoring required to obtain optimal dynamic properties can be remarkably different for cylindrical shells compared to singly curved panels, which have been reported to possess maxima on the boundary of the feasible domain ,20. In al, radius r, thickness h, and fiber angle Simply supported and cantilever cylindrical laminates are considered in this study. N is the number of layers in the laminate, The laminate stiffness properties are modeled using lamination parameters, which are the non-dimensional variables that govern the overall stiffness characteristics . The con1 and V3 ,26, whic1 and V3 (1)V1V3=elations :(2)−1≤V1Using the longitudinal modulus  follows :(3)U1U2UIn terms of lamination parameters and material invariants, the constitutive matrix relating in-plane strains to stresses can be expressed as (4)Cp=U1The constitutive matrix for the transverse shear deformation can be stated as (5)Ct=56y theory .The material properties of the graphite/epoxy laminae (Hercules AS/3501-6) used in the analyses are given in The solutions were computed through finite element analyses, which were performed using in-house tools developed with commercial software MATLAB . The cylinder was discretized with linear 4-node isoparametric shell elements having 3 translational and 2 rotational degrees of freedom at each node. This element is based on first-order shear deformation theory, and the details regarding its formulation can be found in .K and nodal mass matrix M are obtained. One should note that previously derived constitutive matrices :(7)u=uneThen, the natural frequencies of the panel ω¯n=ωIn the calculations, instead of only focusing on the optimal points, the response surfaces over the entire design space were investigated. Hence, full-factorial searches were performed using an approximate resolution of 0.1 for the lamination parameters. This approach ensures the complete exploration of the feasible domain with a total of 315 points.This section covers the results of the free vibration analyses. The focus is on the investigation of the free vibration responses in the lamination parameter space, and the stacking-sequence retrieval is not addressed. In the literature, there are many studies that focus on finding the laminate configurations corresponding to the optimal lamination parameters ,33,34.Prior to the principal investigations, convergence and validation studies were performed for a case taken from the reference , consideaminates , respectNext, the converged fundamental frequency values are compared to the ones presented in . In the This subsection covers the main results for the cylinders having simply supported boundary conditions, which are frequently used to model panel-like regions between the stiffeners of fuselages ,37. FiguThe contour plots reveal several interesting points regarding the dynamic characteristics of cylindrical laminates. One behavior that stands out is the occurrence of the maximum fundamental frequency points at the interior region of the lamination parameter domain in several cases. Such inner points require layer angles of multiple absolute values in the stacking-sequence retrieval process . TherefoAnother noteworthy result is the nonconvex response surface of the second natural frequency, which shows multiple local maxima for The frequency separation responses appear very irregular. The contours exhibit a banded character, which is unusual for free vibration responses although it has been previously observed in forced dynamic analyses ,23. Suchaminates . The mulaminates  or gradiaminates ,43,44) mNext, the shapes of the first two modes are investigated for the cylinders optimized for maximum The results for cantilever cylinders are presented in this subsection. Such structures can represent parts of aerospace structures such as space telescopes, hence their dynamic behavior is practically of interest . Figure For the cantilever cylinders, all points resulting in the maximum first and second eigenfrequencies lie inside the feasible domain. For the lower cylinder aspect ratio  and second natural frequencies of the composite cylinders as well as their difference were obtained in the lamination parameter plane for the first time.In the majority of analyzed cases, the maximum fundamental frequency points occurred at the interior region of the lamination parameter domain, thus requiring layer angles of multiple absolute values in the stacking sequence retrieval. This finding demonstrates that the stiffness tailoring required to obtain optimal dynamic properties can be remarkably different for cylindrical shells compared to singly curved panels, which have been reported to possess maxima on the boundary of the feasible domain.The response surface of the second eigenfrequency appeared to be nonconvex for certain combinations of model parameters. In addition, the frequency separation contours exhibited a banded character, which is unusual for free vibration responses although it has previously been observed in forced dynamic analyses. Such behavior arises from the existence of modes with very close frequencies at certain design points. Increasing the laminate thickness caused the discovered bands to shift and partially vanish.Due to the intricate dynamics of the cylindrical shells, no coherent relations were detected between the shape and order of the modes. This inconsistency has also been experimentally evidenced in the literature. In a particular case, the first two mode shapes even switched their order with the alteration of the thickness, despite both structures being optimized for the maximum fundamental frequency. Such an occurrence also manifests the distinctive influence of the laminate thickness on the free vibrations of the cylindrical shells. Moreover, increasing the thickness was shown to generally decrease the number of circumferential waves within the modes.The presented results give valuable insights on tailoring the stiffness properties of composite cylindrical shells for improving dynamic characteristics. The analyzed simply supported and cantilever cylinders can be particularly related to the intermediate and end sections of circumferentially stiffened aerospace structures, respectively. In the design of such structures, optimization of the eigenfrequencies can facilitate avoiding resonances under operating conditions. However, one should note that the effectiveness of this technique depends on the type and frequency content of the actual dynamic forces. Forced vibration analyses can be performed to predict the functional performance for specific excitation sources.In future studies, additional lamination parameters can be used in the formulation to explore a larger design space. The influence of other geometric values and boundary conditions on the results can also be investigated.


Bacillus subtilis (B. subtilis) inside the ice microneedles to treat mouse models, the practical values of these microneedles are well displayed, indicating their bright prospects in universal drug delivery systems.Microneedles are regarded as an emerging and promising transdermal drug delivery strategy. Great efforts are devoted to getting rid of their material restrictions and imparting them with abilities to carry various drugs. Here, inspired by ice formation in nature and based on characteristics of different frozen materials, the authors present novel ice microneedles made from versatile soft materials using a simple freezing template‐based fabrication stratagem for effective transdermal delivery of diverse actives. Their strategy can convert microneedles with almost all water‐containing components from softness into hardness for guaranteeing satisfactory penetration, thus removing their material component limitations. As all fabrication procedures are mild and actives can maintain activity during these processes, the ice microneedles can carry and deliver various actives from small molecules and macromolecules to even living organisms. They have demonstrated that these ice microneedles can easily penetrate mouse and swine skins using a microneedle injector, with their active‐carried tips left inside after their ice base melts. Thus, by loading heparin, erythropoietin, or biosafe  Ice microneedles are fabricated by a mild and easy‐to‐operate freezing‐template‐replication stratagem and can convert water‐containing components from softness into hardness. Thus, these ice microneedles can be made from versatile soft materials, removing the material limitations; also, they can maintain the activity of carried actives including small molecules, macromolecules, living organisms, etc., ensuring transdermal delivery of diverse actives. Among them, microneedles could penetrate the epidermis without touching blood capillaries and nerve endings, thus enhancing drug absorption in a painless, minimal‐invasive way. Benefitting from these outstanding properties, microneedles have been widely applied to the release of various actives, including small molecule drugs, proteins, and vaccines. However, to achieve successful penetration, the materials of microneedles should satisfy the strength and hardness requirements, which impose great limitations on the choices of their components and thus restrict the applications of microneedles. In addition, many actives are very demanding on the surrounding environments and each has different requirements for loading conditions, while there are no such microneedles that are broadly applicable to the carriage and delivery of almost all actives, including the vulnerable or cell‐related ones. Therefore, it is still highly anticipated to develop versatile microneedles with advanced functions for more generalized applications.Transdermal drug delivery is one of the major drug delivery strategies, which can avoid gastrointestinal tract interferences, extend effecting time, reduce side effects, and simplify administration processes. we present novel ice microneedles with the desired versatile features for all‐purpose transdermal delivery of diverse actives by using a simple freezing template‐based fabrication stratagem, as schemed in Figure Bacillus subtilis (B. subtilis) for anticoagulation, treating anemia or fungal infection mouse models. All these results indicated that the ice microneedles could be ideal candidates for practical and universal transdermal delivery.Here, inspired by ice formation in nature and based on the characteristics of different frozen materials,2Figure In a typical experiment, the ice microneedles were fabricated by introducing a freezing step to the traditional template replication approach, as schemed in The hardness of almost all water‐containing materials was distinctively enhanced in the frozen state. To demonstrate this, different types of materials including water, temperature curing material (Matrigel), light curing material , and ion‐crosslinking curing material  were chosen as representative microneedle materials and their strengths before and after freezing were compared. It was found that without freezing, GelMA and Alg could not be completely demolded, and water and Matrigel could not even form a microneedle shape Figure . BesidesTo further investigate the mechanical strengths of ice microneedles, other qualitative and quantitative experiments were conducted. As demonstrated by the microneedle‐created holes in different layers of a wad of parafilm, the ice microneedles had the ability to penetrate the first parafilm layer with the ratio nearly 100% and could touch as deep as the forth layer Figure . BesidesFigure After penetrating the substrate, the base of ice microneedles would melt, leaving the tips in the substrate, as schemed in Benefitting from the above attributes, various types of drugs could be encapsulated inside the microneedle tips for sustainable release. To visualize the release profile of small molecules, RhB, a model small‐molecule drug, was loaded in the ice microneedles. These RhB‐loaded ice microneedles were then applied to agarose and fluorescence images were taken at specific time points. The increasing fluorescence intensity of the nearby agarose demonstrated that RhB could diffuse from the ice microneedles in a continuous way Figure . BesidesNoteworthily, during the process of applying ice microneedles to the mice, a microneedle injector was employed to assist the microneedle penetration for better and easier operation  were prepared for in‐vitro release tests Figure ,c. WhereB. subtilis, one of the beneficial bacteria which naturally located on human skins and intestinal tracts, was chosen and loaded in the ice microneedles. For evaluating the effects of freezing on B. subtilis viability, the hydrogel blocks containing B. subtilis with or without freezing were dyed with SYTO. It was observed that the relative contents of live bacteria in frozen and unfrozen hydrogels were basically the same, indicating that freezing did no harm to B. subtilis, as shown in Figure B. subtilis could continue to divide and proliferate in the hydrogel after thawing, with the growth trends originally increasing exponentially and then slowing down until saturation due to the limitations of nutrients and space  might be a promising candidate for fungal infection treatments. To verify this, inhibition ring tests were carried out. During the tests, pure paper filter discs, paper filter discs carrying 20 µg ketoconazole , unfrozen B. subtilis‐loaded hydrogel discs, and frozen B. subtilis‐loaded hydrogel discs were placed on petri dishes spread with a lawn of Candida albicans , respectively. After incubation for 24 h at 37 °C, fungistatic zones could be clearly seen in the KCZ group, the unfrozen B. subtilis group, as well as the frozen B. subtilis group, as shown in Figure B. subtilis would not be impeded by freezing and that the ice microneedles could have a comparable antifungal effect to KCZ.Since C. albicans suspension. After that, the mice were randomly divided into four groups and received no treatments (control group), bare ice microneedle (MNs group), KCZ cream (KCZ group), and B‐MNs (B‐MNs group) for 12 days, respectively. During the treatments, the changes of the mouse back skins were recorded. Results showed that fungal infections in B‐MNs group were obviously reduced after the first day of treatment , a large number of pseudohyphae of p Figure . On the p Figure . In addip Figure ,e.B. subtilis should be paid special attention. For this purpose, a high concentration of B. subtilis suspensions was subcutaneously injected to the back of the mice and the changes of their body weights were measured. Slight weight loss of these mice were observed in the initial 2 days, while their body weights steadily gained since the third day, as shown in Figure B. subtilis.As the microneedle tips would be left inside the body, the safety of 3B. subtilis, a type of beneficial bacteria with antimicrobial abilities, have shown satisfactory therapeutic effects in treating fungal infections in immunosuppressed mice. All these features indicated the practical values of ice microneedles in transdermal drug delivery, disease treatments, and many other fields.In summary, inspired by natural ice formation, we generated versatile ice microneedles using a freezing template‐based fabrication approach to get rid of material limitations and realize all‐purpose active delivery. During the fabrication, the microneedles composed of water‐rich materials were frozen before being peeled from the template, so that their structures were maintained and their hardness was distinctively enhanced. It was found that the mechanical strengths of ice microneedles from water, Matrigel, GelMA, and Alg were significantly higher than their unfrozen counterparts and could fulfill the demands of skin penetration. Similar to other biological agents, these ice microneedles should be kept sterile during storage and transport at −20 or −80 °C for a longer time, which was easy to implement. Notably, after being penetrated into the agarose or ex‐vivo skins via an injector, the ice microneedles would gradually melt, with their tips separating from the base and being left inside for continuous release of the carried actives. Additionally, as the freezing process did not destruct the activity of most actives, a wide range of actives could be loaded in and delivered by those ice microneedles, including small molecules, proteins, and live organisms. To be noted, the delivery efficiency of the ice microneedles was determined by their material components and the properties of the carried actives. It has been further demonstrated that the ice microneedles could deliver heparin or erythropoietin for anticoagulation or treating anemic mice. Moreover, ice microneedles loaded with B. subtilis can not only excrete various antifungal agents which aim at specific proteins of fungal cells, destroy the cell walls, and kill the fungi, but also repel and inhibit the reproduction of fungi by preempting space and nutrients. Thus, the B‐MN treatment can avoid the occurrence of resistance. Besides, due to the biosafety of B‐MNs, such treatments can reduce side effects. Also, the relapse of fungal infections is hindered using this treatment. In addition to carrying probiotic bacteria, these ice microneedles are promising to load genetically engineered bacteria to treat other types of diseases including metabolic disorders and cancer. By optimizing the freezing steps and materials, stem cells may also be encapsulated inside the ice microneedles. It is believed that the emergency of ice microneedles can provide lots of inspirations in the development of new‐generation microneedles and shines in the translational medicine field.Compared to traditional fungal infection treatments including topical cream, suppository, oral drug administration, etc., the employment of B‐MNs possesses plenty of advantages. For example, 4−1) was purified by a Milli‐Q water purification system (Millipore). B. subtilis 3610 and C. albicans SC5314 were received from BeNa Biotech Co., Ltd. Male BALB/c mice (about 8 weeks and 20 g) were obtained from Drum Tower Hospital. Animals were treated in strict accordance with the Beijing Administration Rule of Animals in China and had received approval from Animal Investigation Ethics Committee of Drum Tower Hospital.Methacrylate gelatin  was provided by Aladdin. Sodium alginate (low viscosity) and agarose were bought from Alfa Aesar. Matrigel was obtained from Corning. 2‐hydroxy‐2‐methylpropiophenone (HMPP), calcium chloride, and rhodamine B (RhB) were purchased from Sigma‐Aldrich. Fresh porcine skins were bought from the market. Heparin, erythropoietin, cyclophosphamide, cyclophosphamide, and ketoconazole (KCZ) were provided by Drum Tower Hospital. FITC‐BSA was from Zhongkechenyu Biotech. SYTO was offered by KeyGEN Biotech. Sabouraud dextrose agar medium (SDA), nutrient agar medium (NA), and Luria–Bertani culture medium (LB) were purchased from Hopebio Co., Ltd. Deionized water . Other optical images were captured by a stereomicroscope  and a matched CCD camera .To fabricate water‐composed ice microneedles, water was first added to a negative template with ordered cavities. After 5‐min vacuum treatment (vacuum degree: −15 psi), 200 µL water could be filled into the cavities and the extra water was removed using a pipette. A piece of soggy gauze was then placed on the cavities, which was frozen at −70 °C together with the template for 24 h. The ice microneedles would be obtained by removing the template and should be stored below 0 °C. To fabricate GelMA‐composed ice microneedles, 10% (w/v) GelMA solution mixed with 1% (v/v) HMPP was added to the template as microneedle materials. Before being frozen, the GelMA‐filled template was exposed to UV irradiation (365 nm) for 30 s. All other steps were similar to those of fabricating water‐composed ice microneedles. To fabricate Alg‐composed ice microneedles, 4% (w/v) sodium alginate was set as the prepolymer solution of microneedle materials, which was solidified by reacting with 10% (w/v) CaClThe agarose, porcine skin, and parafilm were cut into small blocks, respectively. These blocks and an iron‐made mini‐tamp were then placed at 4 °C for precooling. To observe the holes created by microneedles, the microneedles were pressed to the substrates by the mini‐tamp for 5 s and then were removed quickly. By counting the holes in the agarose, the penetration efficiency of different types of microneedles could be calculated. By using multiple layers of parafilm as the substrates, the penetration behaviors of microneedles on different layers could be obtained.−1. The force recording started once the movable end touched the microneedle tips, and stopped after travelling for 4 s. During the shear force tests, the ice microneedles were fastened sideways on the fixed end, and a sharp blade was glued to the movable end. The approaching speed was about 0.1 mm s−1. Similarly, the force recording began as soon as the movable ends of the microneedle tips contacted each other, and ended until they departed.The compressive and shear forces were measured using a mechanical sensing system . This system contained an upper movable end, a bottom fixed end, and a force sensor. During the compressive force tests, the ice microneedles were placed on the ice‐bag‐cooled fixed end with their tips facing the movable end. The movable end then gradually approached the ice microneedles with the speed of 0.2 mm sn. The ice melted in less than 1 min, and then the microneedle injector together with the base could be removed, leaving the tips inside the skin.The naked skins of the mice first experienced ice compress for over 30 s and were then wiped with 75% (v/v) alcohol for cooling. The base of the ice microneedles was fixed to a microneedle injector beforehand and they were used immediately once taken to room temperature. The tips of ice microneedles would penetrate the mouse skin as soon as the button on the microneedle injector was pressed to release the inside spring and make it extend. It was measured that the force generated by the microneedle injector was about 8 −1 heparin was set as the microneedle material. The mice were randomly divided into three groups. Each group had three mice at each time point. For the control group, the mice were injected with 200 µL saline via tail vein. For the injection group, 200 µL of heparin sodium solution (200 U mL−1) was injected into the mice in the same way. For the microneedle group, the ice microneedles containing heparin  were applied to the backs of the mice. Blood was collected from the eyes of the mice and used for blood coagulation tests after 6 and 12 h, respectively.The GelMA compound hydrogel containing 4000 U mL−1. These hydrogel blocks were then immersed in PBS buffer solution and kept in a thermomixer . At specific time points, 100 µL PBS solution was collected in a 96‐well plate, and another 100 µL fresh PBS solution was supplemented. The fluorescence intensity of the collected PBS solution could be read out using a multimode plate reader . The cumulative release amount over time could be finally calculated from the real‐time fluorescence intensity and the standard concentration‐intensity curve of FITC‐BSA.Hydrogel blocks with the same compositions as the tips of GelMA‐composed ice microneedles were prepared for in‐vitro FITC‐BSA release tests. FITC‐BSA was encapsulated inside these hydrogel blocks with the initial concentration of 1 mg mL−1 erythropoietin was set as the microneedle material. To establish the renal anemia mouse model, the mice were fed with fodder containing 0.75% adenine (300 mg kg−1 body weight per day) for consecutive seven weeks. The ice microneedles containing erythropoietin were applied to the backs of the mice for treatment. Blood was collected from the eyes of the mice and used for blood routine tests after 12 and 24 h, respectively. It should be mentioned that there were 3 mice at each time point for the normal control group, untreated anemia group, and microneedle‐treated anemia group, respectively.The GelMA compound hydrogel containing 5000 U mLB. subtilis was reserved in glycerin‐PBS solution (1:1) mixture at −80 °C and cultured on a NA medium petri dish at 37 °C. One colony was then transferred to a 15 mL centrifuge tube containing LB culture medium mixed with 10% (w/v) GelMA and 1% (v/v) HMPP. To evaluate the bacteria viability in the GelMA compound hydrogel, live bacteria before freezing and 0, 2, 6, and 12 h after recovery were dyed by SYTO and characterized using a laser scanning confocal microscopy .C. albicans was maintained in glycerin‐PBS solution (1:1) mixture at −80 °C and resurrected on the SDA medium petri dish for 24 h at room temperature. The conidia were collected, diluted to 109 mL−1, and spread on SDA medium petri dishes. Pure paper filter discs, paper filter discs loaded with 20 µg KCZ, unfrozen GelMA compound hydrogel discs loaded with 1012 mL−1B. subtilis, and frozen GelMA compound hydrogel discs loaded with 1012 mL−1B. subtilis were placed on the petri dishes, respectively. Each group has five parallels. The diameters of all the discs were 6 mm. The lengths of inhibition rings were measured after incubation for 24 h at 37 °C.12 mL−1B. subtilis was set as the microneedle material. The first step of establishing the fungal infection model was to induce immunosuppression. For this purpose, mice were intraperitoneally injected with cyclophosphamide (150 mg kg−1 of body weight) at day −3 and day −1 (the infection day as day 0), and subcutaneously injected with hydrocortisone acetate (40 mg kg−1 of body weight) at day ‐1. The hair on their backs was then removed and the naked skins were rubbed with blades until the blood oozed. The injured skins were immediately smeared with 109 mL−1C. albicans suspension using sterile swabs for three times. The treatments were conducted once a day and lasted from day 1 to day 12. During the treatments, the mice were randomly divided into four groups (four mice in each group): the control group (receiving no treatments), the MNs group (receiving bare ice microneedles without B. subtilis), the KCZ group (receiving 25 mg of 2% KCZ cream), and the B‐MNs group (receiving ice microneedles with B. subtilis). The everyday changes of mouse back skins were recorded. At day 13, the mice were sacrificed and their infected skin tissues were sampled. Hematoxylin and eosin staining (H&E staining) and PAS staining were conducted for further histological analysis. To calculate skin fungal burden, skin tissues were sliced aseptically and homogenized in PBS. The tissue homogenates were plated in serial dilutions on yeast extract/peptone/dextrose (YPD) agar plates. After incubation at 30 °C for 24 h, colony‐forming units (CFU) were counted.The GelMA compound hydrogel carrying 10B. subtilis, 100 µL of suspension solutions containing 1020 mL−1B. subtilis were subcutaneously injected to the mice. The mice were weighed once a day for 7 days. Their back samples were collected and immersed in neutral formaldehyde at day 1, day 4, and day 7. The samples were then taken out from the neutral formaldehyde, dehydrated, embedded in paraffin, and serially sectioned for H&E analysis and Masson analysis, respectively.To evaluate the safety of n) were provided in the figure legends. To assess the differences between different groups, Student's t‐test was conducted. The difference was regarded to be statistically significant if p < 0.05. SPSS 20.0 software was used to perform statistical analysis.The data were normalized based on the control group. All the presented data were displayed as mean ± SD. The sample sizes (The authors declare no conflict of interest.Supporting InformationClick here for additional data file.


Allergy is an IgE-dependent type-I hypersensitivity reaction that can lead to life-threatening systemic symptoms such as anaphylaxis. In the pathogenesis of the allergic response, the common upstream event is the binding of allergens to specific IgE, inducing cross-linking of the high-affinity FcεRI on mast cells, triggering cellular degranulation and the release of histamine, proteases, lipids mediators, cytokines and chemokines with inflammatory activity. A number of novel therapeutic options to curb mast cell activation are in the pipeline for the treatment of severe allergies. In addition to anti-IgE therapy and allergen-specific immunotherapy, monoclonal antibodies targeted against several key Th2/alarmin cytokines , active modification of allergen-specific IgE , engagement of inhibitory receptors on mast cells and allergen-specific adjuvant vaccines, are new promising options to inhibit the uncontrolled release of mast cell mediators upon allergen exposure. In this review, we critically discuss the novel approaches targeting mast cells limiting allergic responses and the immunological mechanisms involved, with special interest on food allergy treatment. Nowadays, over 20% of the world population actively suffers from one or more allergies, among which approximately 10% is living with food allergy .Anaphylaxis is a systemic reaction involving two or more organ systems, occurring shortly after the exposure to the culprit allergen. It manifests with a plethora of symptoms, including hives, angioedema, shortness of breath, vomiting, hypotension and cardiovascular collapse, which is potentially life-threatening and requires emergency treatment . The comMC activation is also the cause of the delayed release of newly synthesized cytokines and chemokines , 6, thatIn addition to their prominent role in the genesis of allergic and anaphylaxis symptoms, MCs actively participate to the complex interplay of innate and adaptive immunity in the defense against pathogens, wound healing and tumor surveillance –19. Due Strategies to pre-emptively curb MC activation are currently being explored for therapeutic purposes. Allergen-specific immunotherapy, recently developed biologics, a combination of both, and the discovery of new druggable targets are the most promising options available to treat food allergy.The purpose of this review is to highlight the different immunological mechanisms targeting IgE-mediated MC activation as a therapeutic option for the treatment of food allergy, with particular focus on peanut allergy. However, two crucial preliminary considerations should be made. First, no treatment option currently available is uniquely targeting MCs. In fact, receptors inhibiting MC activation are shared among different cell types, and cytokines and other soluble mediators have pleiotropic effects affecting multiple cell populations at once. Second, any treatment inhibiting IgE-mediated MC activation should also take into consideration the broader implications and the potential loss of MC protective functions. Hence a benefit/risk assessment should be made, especially when considering highly disruptive interventions, like active MC depletion, not covered by the present manuscript .via disulfide bridges (10–1011 M−1) and the slow dissociation rate , bound  bridges . Several bridges –40. IgE  bridges , 42. IgE bridges . Given tion rate , 45, the domains . FcϵRI i domains –50. A ti domains , 51, 52. domains .Furthermore, occupancy of the FcϵRI receptor is crucial to ensure its expression on the cell membrane by MCs and basophils, as shown by mechanistic studies demonstrating increased FcϵRI expression upon IgE binding due to decreased FcϵRI endocytosis and degradation , 54–56. FcϵRI is constituted by one alpha and one beta chain on MCs and basophils, or a single alpha chain on monocytes and dendritic cells , 58, 59,5 molecules per cell measured on LAD2 MCs , genetically engineered antibody mimetic proteins, recognize IgE Cϵ3 domains with high specificity and affinity, and have been shown to be 10,000-fold more efficient than omalizumab in dissociating IgE complexes episodes –165  inhibitors, significantly reduced degranulation and cytokine production in human MCs and basophils, decreased bronchoconstriction in isolated human bronchi, and proved effective in preventing anaphylaxis in a passive systemic anaphylaxis model using humanized mice , 188 Ta. To thisCurrent evidence suggests that IgE from atopic individuals show an increased sialic acid content, contrary to subjects with no atopy, thus pointing at an important role of sialylation to determine IgE allergenicity . Neuramivia the phosphorylation of Janus Kinases   , 195. In3, Tyk2) –198.Alongside classical Th2 cytokines, MCs respond rapidly to tissue damage signals such as IL-33 and thymic stromal lymphopoietin (TSLP), alarmins produced mostly by epithelia, innate lymphoid cells and, in some conditions, by MCs themselves , 200. ILTSLP shares common properties with IL-33. They both promote the proliferation and differentiation of MC progenitors , and the−/− mice  of the CD33 family and CD300a. Most inhibitory receptors exert broad suppressive functions on MC activation, with the exception of FcγRIIb and CD200R, producing allergen-specific inhibition.via the recruitment of tyrosine phosphatases with Src homology 2 domains , or PI3K binding-motifs  domains that actively inhibit the phosphorylation of the Syk pathway g-motifs , 214, divia the skin compared to the gut route, as currently suggested by the dual exposure hypothesis , FcγRIIb (CD32b), and FcγRIIc (CD32c), only FcγRIIb is inhibitory. In mice, IgG binding to FcγRIIb inhibits antigen-specific IgE-mediated activation and Th2 cytokine production by MCs, IgE antibody production by B cells –218, whipothesis , and divpothesis .in vitro studies using human basophils, bone marrow-derived MCs of human FcϵRIα-transgenic mice, FcϵRIα-transfected human cell lines and the HMC-1 mast cell line , ceramide, sphingomyelin (CD300f), released by apoptotic, tumor or infected cells . In addiAllergen-specific immunotherapy (AIT) is the only disease-modifying intervention currently available to treat some allergic conditions, like insect venom allergy, allergic rhinitis and asthma due to respiratory allergy to pollens and house dust mites –237.AIT consists in the repetitive exposure to escalating doses of native allergen extracts, which might induce generalized MC and basophil activation. The risk of eliciting an anaphylactic episode is mitigated by starting with very low allergen doses, by being performed only by trained professionals and in safe conditions under careful monitoring of potential early signs of systemic reaction , 238. ThThe concerted activity of cells from both innate and acquired immunity contributes to the efficacy of AIT –36, ultivia OX40L receptor engagement  via the oral route  administered al route .Recently, the first peanut allergen powder formulation (AR101) was approved for peanut AIT by the U.S. Food and Drug Administration and European Medicines Agency , 252, anTo increase AIT safety in food allergy, newer therapeutic strategies involve the combination of AIT with biologics. Evidence suggests that omalizumab administered during AIT reduces the risk of severe reactions and facilitates AIT , 99, 101However, studies on long-term use of omalizumab in cow’s milk AIT proved long-term omalizumab add-on treatment not being cost-effective, albeit the higher safety profile  , such as Toll-like receptor ligands , viral-attenuated molecules, Siglec-engaging tolerance-inducing antigenic liposomes (STALs) and nanoformulations, is used as adjuvant immunotherapy to elicit allergen-specific tolerance .via allergen-coding DNA particles, exploiting the natural immune pathways leading to the production of IgG to promote long-lasting tolerance  Medical Research Council Doctoral Training Partnership (MRC-DTP) studentship. SB-P received funding from MRC (MR/S036954/1).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cyber–physical systems (CPSs) are generally considered to be the next generation of engineered systems. However, the actual application of CPSs in the Architecture, Engineering and Construction (AEC) industry is still at a low level. The sensing method in the construction process plays a very important role in the establishment of CPSs. Therefore, the purpose of this paper is to discuss the application potential of computer vision-based sensing methods and provide practical suggestions through a literature review. This paper provides a review of the current application of CPSs in the AEC industry, summarizes the current knowledge gaps, and discusses the problems with the current construction site sensing approach. Considering the unique advantages of the computer vision (CV) method at the construction site, the application of CV for different construction entities was reviewed and summarized to achieve a CV-based construction site sensing approach for construction process CPSs. The potential of CPS can be further stimulated by providing rich information from on-site sensing using CV methods. According to the review, this approach has unique advantages in the specific environment of the construction site. Based on the current knowledge gap identified in the literature review, this paper proposes a novel concept of visual-based construction site sensing method for CPS application, and an architecture for CV-based CPS is proposed as an implementation of this concept. The main contribution of this paper is to propose a CPS architecture using computer vision as the main information acquisition method based on the literature review. This architecture innovatively introduces computer vision as a sensing method of construction sites, and realizes low-cost and non-invasive information acquisition in complex construction scenarios. This method can be used as an important supplement to on-site sensing to further promote the automation and intelligence of the construction process. With the continuous development of computer science, researchers have become increasingly interested in the use of digital virtual technologies in the construction industry. Due to the growing demand for information exchange on the construction site, cyber–physical system (CPS) architecture has become a highly promising approach. Cyber–physical systems (CPSs) refer to the integration of physical processes and computation ,2,3. CPSHowever, the application of the current CPS architecture on the construction site still faces many limitations. Although the widespread application of building information modeling (BIM) technology in construction projects has greatly facilitated the establishment of the cyber side of CPSs, how to achieve data exchange and coordination from the physical side to the cyber side based on multiple sensors is still a major problem due to the decentralized and complex nature of construction sites. Cost is also a problem in the application of CPS in construction sites. Contractors still have doubts about the benefits of their investment at the CPS level. On the other hand, at the researcher, professional, and institutional levels, barriers have resulted in narrowly defined, discipline-specific research and education venues in academia for the science and engineering disciplines. Research of CPSs is partitioned into isolated sub-disciplines . TherefoComputer vision (CV) allows computers to obtain high-level, abstract, and computable information from images or video. Currently, deep learning-based CV methods are widely accepted. Since the demonstration of convolutional neural networks (CNN) for image classification tasks in 1998 ,11. At tThe innovation and development of CPS will require computer scientists and network professionals to work with experts in various engineering disciplines including control engineering, signal processing, civil engineering, etc. . These aIn this paper, a review of the state-of-the-art applications of CPS in the construction industry is presented, along with an analysis of the currently existing knowledge gaps that affect the further application of CPS on the construction site. Afterward, based on the review of computer vision technology application in construction, a method to establish a bridge for the transmission of information from the physical side to the cyber side of CPS using the computer vision method is proposed. For the application of CPS in the construction industry, this paper focuses more on the combination of the construction process and CPS to enable better intelligent management of this important phase of construction. This CPS framework focuses on the construction process, and innovatively introduces computer vision as a sensing method of the construction site, and realizes low-cost and non-invasive information acquisition in complex construction scenarios. The feasibility of this method was further analyzed. Finally, the implementation method of a computer vision-based CPS system is discussed and conclusions are drawn. This method can be used as an important supplement to on-site sensing to further promote the automation and intelligence of the construction process.This article conducts an overview study of CPS applications at current construction sites. Since the sensing of the physical environment is an important part of CPS, and one of the main obstacles to the current application of CPS on construction sites is that site sensing is affected by complex environments, this paper is dedicated to a CV-based approach to site sensing. For these reasons, the scope of the literature in this paper covers two main areas: the CPS and the application of CV in construction site sensing.This paper collects and analyzes the literature from academic publications on the application of CPS in the construction industry and the application of CV methods to perceive construction behavior on the construction site. The methodology used in this paper refers to the collection and analysis of the literature in ,16. The Of these, steps 1 and 2 will be discussed in this section, and the collected literature will be initially organized and analyzed. Step 3 will be analyzed and summarized in detail in The procedure of this research can be seen in The literature collected included two main parts: cyber–physical system(s) and computer vision. Both were narrowed down in research areas to “CONSTRUCTION BUILDING TECHNOLOGY.” After keyword searching, the literature was further filtered based on the title and abstract to obtain content relevant to this topic. Finally, a total of 110 references were cited in this paper. Of these, 19 were published after 2020, 46 in 2018–2019, and 24 in 2015–2017. The main sources of the literature include Automation in Construction (41), Computer-Aided Civil and Infrastructure Engineering (5), Engineering, Construction and Architectural Management (6), Journal of Computing in Civil Engineering (3), Sensors (3), and Advanced Engineering Informatics (3). All the literature searched is from Web of Science (WOS).CPS is generally considered to be the next generation of engineered systems. It is a controllable and scalable system. The abilities of computing, communication, and control are deeply integrated on the basis of information acquisition . CPS is Cyber–physical systems integrate computing, communication, sensing, and actuation with physical systems to enable time-sensitive functions and interaction with the environment and human . CPS is It is worth noting that the CPS does not directly reference either implementation approaches or application. Instead, it focuses on the fundamental intellectual issues that combine the engineering traditions of the cyber and physical worlds . This naFirst, CPS is a system that integrates on the basis of existing physical, network, and computer system architectures. In addition, abstraction and modeling of communication, computational, and physical dynamics at different time scales and sizes are required to build CPS architectures . In the The actuator network in CPS should consist of multiple actuator units and control nodes. The control nodes are responsible for receiving commands and sending them to a specific actuator in order to adjust and control certain physical properties of the physical world . In the The information system is the core of the CPS. For the construction industry, the virtual model of the building is the core of the information system. The integration of digital models and physical construction processes is now showing great promise to improve the productivity and safety of the construction process through resource tracking and activity monitoring . DigitalAfter clarifying the concept and architecture of CPS, the current status of CPS applications in the construction field needs to be summarized in the context of the AEC industry. This section summarizes the literature to obtain the sensing approach and feedback control methods adopted for CPS applications in construction sites. In First, for safety management, CPS shows good prospects. Congwen Kan et al.  exploredFrom the aspect of building performance management, Andrea Bonci et al.  proposedFor SHM and the structural test domain, Ruiyang Zhang and Brian M. Phillips  presenteAt the level of an overall perspective, Raihan Maskuriy et al. ,39 discuSimilarly, analogous to BIM and city information modeling (CIM), CPS can also be applied to broader urban scenarios, providing a fundamental approach to the establishment of smart cities . DeployiState-of-the-art studies have shown that although CPS has been tested in the construction field, the current state of CPS still does not allow for its widespread application, especially for on-site construction processes. This problem is the result of a combination of factors. The AEC industry is traditionally characterized by a high degree of process diversity. Compared to manufacturing, the construction industry has a lower capacity to change as well as new technologies .As above-mentioned in the literature, currently, CPS is more widely used in domains such as building energy management ,48. ThisFor construction sites, existing methods are not acceptable to contractors in terms of cost and difficulty. An example can be seen in the existing research . The decFor the specific environment of the AEC industry, it is necessary to propose a novel approach to sense the construction site in order to further develop the application of CPS in the construction process.Computer vision is a technology that allows computers to learn to “watch” and to have human-like “vision” capability. Computer vision methods allow computers to extract higher-level, abstracted information from huge amounts of image or video data. Currently, there are many different tasks in the field of computer vision such as object detection, instance segmentation, semantic segmentation, object tracking, etc. depending on the input image information and the required output information. After the concept of deep learning was introduced, computer vision methods based on deep learning, especially convolutional neural networks, have been rapidly developed. Deep learning and convolutional neural networks have brought a great revolution in the field of computer vision, and it is this revolution that provides a far better foundation for the application of computer vision in construction sites. Convolutional neural network-based methods now play an important role in many fields including object detection, instance segmentation, and tracking.After reviewing the computer vision methods, it was found that object detection and the instance segmentation method can benefit computer vision-based construction site sensing. In addition, tracking methods for various types of objects are equally important.Object detection is a method to precisely estimate the concepts and locations of objects contained in each image to gain a complete image understanding. It is able to provide valuable information for the semantic understanding of images and videos . CurrentThese two types of methods each have different advantages and disadvantages. In general, the two-stage approach performs better at the level of mAP and object location accuracy; however, it consumes more computing capability and time. Although tricks can be used to make it better in real-time, overall, the one-stage method can perform the detection task more quickly with better real-time performance .The development of the two-stage method has a clear line of succession. From R-CNN to Mask-R-CNN, the development is established based on the previous generation of technology. The two-stage method includes R-CNN , SPP-netInstance segmentation can be considered as a further extension of object detection. In object detection, a specific object in an image is localized by a rectangular bounding box. However, in this localization method, it is difficult to specify the exact location of the object in complex states. In practical applications, object boundaries are also important information. The algorithm represented by Mask-R-CNN  achievesCurrently, with the increasing demand for digitalization and intelligence in the construction industry, the research on the application of deep learning-based computer vision methods in construction projects has been developing rapidly. The construction site is complex and the current application of computer vision in construction sites generally selects a specific entity or several interrelated entities at the construction site for the corresponding site sensing and information acquisition. Researches carried out on the construction site vehicles, construction machinery, and workforce detection show that the use of computer vision methods can effectively obtain construction site human–machine information, and this information will play a key role in intelligent management for construction.Depending on the selected construction site entity, the sensing of the construction site can be divided into the following components: workforce, equipment, materials, construction methods and technology, environment, and quality. The CV algorithm can also be further categorized based on the categories of information acquired when applied to these different entities, as shown in The workforce is the most important factor on the construction site. Currently, the level of automation in the construction industry is relatively low, and the need for labor is still high. This also means that the management of the workforce is one of the most important out of all aspects of site management. The productivity of workers on site is always a concern for managers. In addition, personnel safety is another noteworthy issue. As shown in There is a wide variety of equipment at construction sites, and its tracking and monitoring play an important role in site management. For heavy equipment on-site such as tower cranes, their operational status has a major impact on both site safety and productivity. Identifying and tracking construction materials is essential in the construction process. Management of the transportation, lifting, and installation of building materials requires access to a variety of information about their location, quantity, and condition. The use of computer vision on construction sites can provide the information needed for management in a non-intrusive way. In busy and complex construction sites, the non-intrusive, low-cost advantages of visual methods can be better demonstrated. Construction activity is the basic component unit of the construction process. For CPS, to achieve a digital representation of the production process, the identification of on-site construction activity is necessary. However, construction activity involves interactions between multiple entities and is more complex than the recognition of a single entity. Visual methods for complex construction activity still need further development. The object detection method only acquires the position of the object in 2D image pixel coordinates, but both the implementation of construction management and the establishment of CPS need the actual 3D coordinates of the object as the basis. Therefore, the 3D reconstruction of the construction site is very necessary. There are a number of methods available to achieve this goal. The detection of damage on structural components of existing buildings or buildings under construction based on computer vision methods has been proven to be an effective method. However, there is still no effective method for construction quality inspection during construction. This field is still underdeveloped. In general, although there have been studies on construction safety management based on computer vision, the focus of this research is still at the level of identifying image features  of the construction site rather than a systematic approach to management. The combination of CPS can better accomplish this task. The review above shows that computer vision is currently being tested in the construction industry. As an emerging cross-discipline, this field is developing very rapidly. However, the application of computer vision on construction sites is still in its infancy. At present, researchers are still devoted to the exploration of computer vision in the construction field. Although these methods have accomplished their objectives using computer vision methods in construction site scenarios, they lack a systematic solution and do not form an effective closed-loop control, and some of the studies have only accomplished the initial goal of identifying and acquiring information, but not the subsequent reconstruction of construction scenarios or the simulation and analysis of the construction process. Similarly, there is a lack of research on how to further utilize the information extracted from the images by computer vision methods to systematically improve the intelligence of the construction process. Among the above literature, only  conducteThis knowledge gap limits the application of computer vision in construction. There is a need for an architecture that can effectively apply the information obtained through CV to better facilitate relevant research.During the construction stage, CPS creates a looped connection between stakeholders that provides access to virtual models via mobile devices and facilitates decision-making . CPS is Therefore, after completing the review of the current state of application of CPS and computer vision methods on construction sites, this paper concludes that implementing a relatively low-cost construction site perception system based on computer vision methods and applying it to the construction of CPS architectures is a very promising option. Zhenhua Zhu et al.  found thSecond, camera systems cover a larger area than RFID or IoT-based sensor systems and are more advantageous for use on construction sites where the layout is dispersed. Cameras with auto-tilt systems can also be better adapted to construction sites where the location of the construction process is constantly changing, focusing on key points of the construction site.Third, computer vision-based method is non-invasive. This solution is more flexible than invasive detection such as RFID or wearable devices and also reduces the cost of equipment placement. Because there is no need to pre-arrange on the object to be detected, it has a better ability to respond to unanticipated situations.Finally, the information acquired by the camera, although requiring more computing power to process, is richer than that of single-function sensors and RFID. The construction process is a complex one, and it is difficult to obtain a complete picture from a single sensor. However, vision-based image information contains information that can be used to identify and judge the construction process. Just as in traditional human-based site management, a construction worker can easily judge the construction process visually. The goal of the computer vision approach is precisely to give computers processing power similar to human vision.The 3D laser is also a feasible method on construction sites. 3D point cloud is more detailed on-site information. However, the cost and detection range make it difficult to use for construction scenarios.In crowded and busy construction sites, vision-based methods of acquiring information have a unique advantage over other methods. With careful planning, hundreds of RFID tracking tags can be replaced by a small number of cameras placed on the construction site, significantly reducing the cost of information acquisition .(1)Sensing layer: The function of this layer is to obtain primary information from the construction site and consists mainly of surveillance cameras installed at the construction site. At the same time, 3D lasers can be added to supplement the information acquisition channel in key areas. Other sensors can also be integrated into the system as additional information to obtain a more detailed site perception. The camera layout needs to cover as much of the main construction area as possible, with multiple viewpoints for areas where the workforce and equipment are concentrated as well as an overall view of the construction site.(2)Process layer: Although visual data are rich in information, it is also more difficult to process than other methods. Especially for the complex environment of a construction site, the information required by the system is at many different levels, and the extraction of high-level, abstract, and computable information from the visual data requires a combination of different processing methods. Category and location detection, edge detection, and activity/state recognition of workforce and equipment require a composite approach. This layer is the computationally intensive part of the system, and the extraction of the various features in images needs to be considered in order to minimize the computational stress.(3)Data layer: The function of the data layer is to integrate, archive, and store the original data  with the real-time data from the site during the construction process. The original BIM needs to be matched with the real-time site conditions to derive the actual construction schedule information. In addition, the construction activity information obtained on-site also needs to be integrated with BIM to be used in subsequent analysis.(4)Visualization layer: Due to the characteristics of the construction site itself, the closed-loop control of the site must be carried out by the workers on the construction site. The current building construction process is still in a human-dominated state. Construction sites also lack mechanical devices that can provide direct feedback control. Therefore, the feedback of information is mainly through two ways of the visualization layer. First, for the information directly related to construction site personnel such as safety information, this type of feedback is provided directly through the mobile devices or wearable devices of the on-site workers. The CPS environment typically includes humans, and humans function in a different way to the other components of a CPS. The architecture must support a variety of modes of human interaction with CPS to include the human as the CPS controller or partner in control . The besBased on the above reasons, the following CPS framework is proposed in this paper as a solution to the current difficulties in applying CPS in the construction field. The CPS architecture proposed in this paper places more emphasis on the mirror mapping between physical and digital entities on the construction site, and aims to establish a virtual construction site as well as a mirror relationship and synchronous mapping from a physical to virtual construction site through site sensing. First, For the information that must be involved at the decision-making level such as productivity management, schedule control, and construction quality, the feedback control is provided through visual BIM presented directly to the decision-maker. This feedback mode is mainly determined by the current construction automation level and management mode. In the future, the construction site with higher automation can further optimize it to realize more intelligent and automatic decision-making and feedback.This four-layer structure above provides a generalized framework for the construction process CPS. Considering the actual situation of the construction site, except for a few mechanical equipment, the construction site lacks actuators. This phenomenon is caused by the level of automation on site. This framework incorporates person–system and person–environment interactions into the system through a visualization layer that provides instructions or warnings to the on-site workforce as feedback. This framework is only a preliminary idea to achieve the co-application of CV and CPS. It is expected that this framework will provide ideas for the application of computer vision on construction sites and encourage the combination of CPS and CV methods to achieve smarter construction sites.Although computer vision-based site sensing has many of the above-mentioned advantages, its current application on construction sites also has certain limitations. In order to overcome these limitations, there are still obstacles that need more novel technology to overcome.First, the layout of the construction site frequently changes with the construction progress. From the time that equipment enters, the layout of the site will be constantly adjusted as the construction phase progresses. The working surface/temporary yard/temporary facilities will also change constantly during construction, and the number of tower cranes will also increase or decrease as construction proceeds. As cameras are often placed on construction equipment/facilities, these physical changes to the construction site will lead to additional challenges to the camera system and it will be difficult to achieve complete monitoring. Adjustments would also create more workload.Second, the issue of occlusion during construction is also a major impediment to the application of visual methods. The problem of occlusion is multi-layered, starting with the problem of objects in front blocking objects in the rear in a localized area of the work surface. This can be solved by placing the camera at multiple views. The other level is the macro-level blocking of the existing work surfacing over the completed floor. Ensuring adequate views will greatly increase the number of cameras that need to be placed. The reliability of computer vision methods for extracting information is also an important issue.Finally, visual methods for processing on-site video require more computing power. In addition, there is no appropriate method for calculating the different layers of information that need to be extracted, which leads to repetitive computation and wasted computing power. For the large-scale application of this CV-based approach, the above-mentioned knowledge gaps must be filled. Better solutions are still waiting to be proposed.In addition, the current construction site automation is still at a low level, and a large amount of work needs to be done manually by the on-site workforce, which leads to a great limitation of the control method from the information side to the physical side of the CPS. Currently, feedback control can only be achieved through visualization and instructions to the on-site workforce to transfer information from the cyber side to the physical side. Although this approach enhances the digital and intelligence level of the construction site, there is still a gap between this approach and the automation control expected from CPS. This is a compromise due to the complexity and decentralized nature of the construction site. The solution to this problem is to look forward to the further development of automated construction, so that actuators that can be connected to the cyber-side on the construction site can play a major role.In this paper, an overview of the state-of-the-art computer vision-based construction site sensing methods is presented to further expand the application of CPS in the AEC industry. Based on the review, in-depth issues affecting the application of CPSs on construction sites and current knowledge gaps are stated. It was found that computer vision is an excellent method of construction site perception. The potential of CPS can be further stimulated by providing rich information from on-site perception using computer vision methods. The main contribution of this paper is to propose a CPS architecture using computer vision as the main information acquisition method based on the literature review. This architecture innovatively introduces computer vision as a sensing method of a construction site, and realizes low-cost and non-invasive information acquisition in complex construction scenarios. This architecture can digitize the construction process and provide an information base for intelligent construction management. This method can be used as an important supplement to on-site sensing to further promote the automation and intelligence of the construction process. Finally, the limitations and possible obstacles to the application of the above method are also discussed.


Predictive coding theories argue that deviance detection phenomena, such as mismatch responses and omission responses, are generated by predictive processes with possibly overlapping neural substrates. Molecular imaging and electrophysiology studies of mismatch responses and corollary discharge in the rodent model allowed the development of mechanistic and computational models of these phenomena. These models enable translation between human and non-human animal research and help to uncover fundamental features of change-processing microcircuitry in the neocortex. This microcircuitry is characterized by stimulus-specific adaptation and feedforward inhibition of stimulus-selective populations of pyramidal neurons and interneurons, with specific contributions from different interneuron types. The overlap of the substrates of different types of responses to deviant stimuli remains to be understood. Omission responses, which are observed both in corollary discharge and mismatch response protocols in humans, are underutilized in animal research and may be pivotal in uncovering the substrates of predictive processes. Omission studies comprise a range of methods centered on the withholding of an expected stimulus. This review aims to provide an overview of omission protocols and showcase their potential to integrate and complement the different models and procedures employed to study prediction and deviance detection.This approach may reveal the biological foundations of core concepts of predictive coding, and allow an empirical test of the framework’s promise to unify theoretical models of attention and perception. The ability to learn associations between stimuli and behavior is the main selective pressure on central nervous systems across species and appears to be among the core functions of the neocortex  interneurons are known to modulate sensory activity based on top-down intracortical input , mid latency negativities (MMN-like and N2-like), and later positive components (P3-like). These omission responses have been interpreted as representing a range of processes, which are not mutually exclusive. Bullock and colleagues studied omission responses extensively across species  are represented by different pyramidal populations, depending on their acoustic features. The different populations are interconnected and are also reciprocally connected with local interneurons. The interneurons have inhibitory synapses on similarly and dissimilarly tuned excitatory and inhibitory populations. These reciprocally connected representational nodes respond to stimuli based on their respective activity history, generating responses to change. The node output can be the input for a hierarchy of such nodes, capable of processing more and more abstract forms of regularity and deviation.Besides connectivity, the production of deviance-specific responses relies on at least two other phenomena. One is short-term plasticity and SSA of excitatory units as suggested by Chien et An important notion to test is whether these nodes undergo constant endogenous activation and modulation, which would be revealed by omission responses. The heterogeneity of results from omission studies employing methods with different sensitivity may stem from the modulation of these nodes by motion, multimodal associations, attention, behavioral state, and other ongoing sensory processes. Alternatively, the heterogeneity of omission responses could indicate unrelated, non-overlapping mechanisms. A systematic model-driven investigation of omission responses is necessary to differentiate between these options. Opto- and chemogenetic manipulation of selected neuronal populations at different levels in the sensory pathways, in combination with stimulus omission, will allow the assessment of whether stimulus-specific populations act as deviance detectors. If the proposed models are accurate, the comparison of omission and mismatch responses should reveal two kinds of activity: focal activity of a stimulus-selective population at deviant onset (mismatch only) and distributed activity of multiple such populations at the time the standard stimulus is due (mismatch and omission). Furthermore, these techniques can be employed to assess the contribution of different processing stages along the sensory pathway to deviance detection phenomena in the cortex. Another important experimental step is the manipulation of NMDA receptors with proper controls to assess their role in predictive processes. In particular, whether they are implicated in both omission responses and MMN, specifically for regularity formation rather than deviance detection as predicted by Chien et al. , and wheIn conclusion, model-mediated interaction between human and animal research is informative concerning the cortical generators of MMN and corollary discharge. The underlying circuitry does in principle support omission responses as well. Biologically inspired computational models allow the translation from circuit activity measured in animals to the macro-level responses observed in human studies. Animal implementation of cognitive neuroscience protocols, in conjunction with cell-type-specific imaging methods, is thus necessary to determine the substrates of deviance detection phenomena. These methods have already demonstrated the importance of feedforward inhibition in the generation of mismatch responses. It is necessary to assess whether this and other deviance detection phenomena, like corollary discharge and omission responses, are generated by the same local cortical circuitry, or by similar but non-overlapping networks, or by unrelated mechanisms. Re-use of the same circuitry is consistent with the current understanding of cortical structure and function, and its conservation across species and modalities. Among deviance detection protocols, omission protocols allow a focus on local circuit activity and its top-down modulation by evoking deviance detection in the absence of sensory input. The silencing of bottom-up input is an important tool to dissect neuronal circuits and to explore the substrates and empirical consistency of prediction and prediction error, the main actors of predictive processing theories. Interactionist investigation of cortical circuitry across species with omission protocols would provide the biological foundations of core concepts in the predictive processing framework and an empirical test of the framework’s unifying potential. These are important objectives, given that predictive theories of brain disorders are increasingly influential in the clinical community. A substrate-level understanding of their mechanisms is necessary to make these theories empirically testable and to open new avenues of diagnosis and treatment.All authors contributed equally to the article and approved the submitted version.The authors acknowledge support from the German Research Foundation (DFG) and the Open Access Publishing program of the Leipzig University.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Marine ice-cliff instability could accelerate ice loss from Antarctica, and according to some model predictions could potentially contribute >1 m of global mean sea level rise by 2100 at current emission rates. Regions with over-deepening basins >1 km in depth  are particularly susceptible to this instability, as retreat could expose increasingly tall cliffs that could exceed ice stability thresholds. Here, we use a suite of high-fidelity glacier models to improve understanding of the modes through which ice cliffs can structurally fail and derive a conservative ice-cliff failure retreat rate parameterization for ice-sheet models. Our results highlight the respective roles of viscous deformation, shear-band formation, and brittle-tensile failure within marine ice-cliff instability. Calving rates increase non-linearly with cliff height, but runaway ice-cliff retreat can be inhibited by viscous flow and back force from iceberg mélange. Ice-cliff failure that leads to marine ice-cliff instability could accelerate Antarctic Ice Sheet retreat. Here, the authors use 3D glacier models to investigate ice-cliff failure, derive a retreat rate relationship, and quantify mélange back force necessary to suppress ice-cliff failure. These calving faces may be susceptible to structural failure if glaciostatic stress exceeds the yield strength of ice (~500 kPa to 1 MPa), with this stress threshold being exceeded at a cliff height of ~100 m8. Marine ice-cliff instability (MICI) will initiate  if progressively taller cliffs are exposed through each cycle of failure9. Here, we make a distinction between ice-cliff failure, leading from stress imbalances at glacier termini, and marine ice-cliff instability, or the instability of a glacier or ice stream resulting from runaway ice-cliff failure. Determining if and how MICI will occur has recently challenged the glaciology community10, with conclusions being difficult to draw since such cliff heights are outside of the modern observational record. The importance of clarifying whether MICI will materialise is demonstrated by ice-sheet model output showing enhanced and alarming rates of global mean sea-level rise (SLR) when ice-cliff failure is represented with a simple parameterization in models of the Antarctic Ice Sheet1.One prospect for a future Antarctica is the exposure of immense ice cliffs following the loss of buttressing ice shelves and continued grounding line retreat13. Continuum models have recently been used to investigate processes and rates of MICI retreat, with cliff failure assumed to occur if strain rates or shear stress exceed threshold values14. However, the possibility that MICI could occur through a spectrum of failure modes means that reliable parameterizations must be based on modeling of these specific processes.It is impractical to incorporate the granularity of the complex MICI process in continental-scale ice-sheet models, so reliable parameterizations of the key processes are needed to constrain SLR predictions16, the standard brittle-elastic implementation of the Helsinki Discrete Element Model (HiDEMbe)18, and a second, brittle visco-elastic implementation (HiDEMve). HiDEM represents glaciers as assemblages of densely-packed particles that are connected by beams that will break if strain, bending, or torsion, in combination, exceed a user-defined threshold. HiDEMbe is used to simulate the predominantly tensile failure of glaciers, whereas HiDEMve is designed to simultaneously model viscous deformation and fracture in a simplified form by partly decreasing or weakening the elastic-brittle bond connections while compensating with a short-range cohesive force that allows for viscous shear deformation. Ice properties are varied in HiDEM by adjusting beam width, fracture threshold and the degree of damage. The latter is represented as the percentage of initially broken bonds. More detailed descriptions of the HiDEM implementations are provided in the Methods and Supplementary Note be19 as long as stresses are not high enough to initiate damage via shear-fracture. Shear failure is observed when the shear strength is reduced in HiDEMbe or a thickness threshold is reached in HiDEMve. Our second contribution is the provision of back force values that mélange must exert on a calving face to halt structural failure. Lastly, we provide a retreat rate parameterization to represent ice-cliff failure in ice-sheet models. The parameterization was derived through a workflow that simulates the entirety of an ice-cliff failure event, which allows for the explicit determination of both calving magnitude and the duration of a calving cycle.Employing three high-resolution 3D models and idealized glacier geometries, we conduct a series of simulations to investigate modes of structural ice-cliff failure. Our model suite consists of the full-Stokes continuum model Elmer/IceTice) and bed friction conditions (B). The standard parameter settings and set-up of HiDEMbe combine to represent ice that is strong in shear  and undamaged 20 (see Methods).We simulate the deformation and failure of idealized glaciers grounded on a retrograde slope with varying ice temperature  and a corresponding increase in cliff height (Hc). We discuss our results in terms of Hc, noting that references or values could be similarly described in terms of H. We test for failure across a range of Hc and Tice = −20, −10 and −5 °C given normal basal slip conditions (Bn). We also test for failure with low  and high  basal friction conditions while maintaining Tice = −20 °C. See Methods for further information on the model workflow and parameter assignment.For strong and undamaged ice, the failure of vertical calving faces is not observed in HiDEM11  is dominated by buoyancy-driven calving, consistent with previous modeling investigations into the spectrum of glacier calving styles19. Buoyancy-driven calving, as described in Benn et al.19, occurs when a glacier terminus is in hydrostatic disequilibrium and buoyancy forces lead to upward rotation, basal fracturing and iceberg calving via outward block rotation. We further detail the differences between buoyancy-driven calving and the modes of structural ice-cliff failure in Supplementary Note Structural ice-cliff failure is observed for ld Hc ≤ 17 m is doHc, warming Tice, or increasing bed friction  in Table B, as well as degree-of-buoyancy and surface slope, are discussed further in Supplementary Note For glacier thicknesses that are susceptible to ice-cliff structural failure, simulations show the ‘time to failure’ (TtF) decreasing with increasing on Table . This ise Ĉ, m d− in TableH and Hc of calving fronts. The magnitude of change will be dictated by a number of ice and environmental conditions . For the standard basal slip conditions used in this study, test simulations are run as examples of how the timing and mechanism of succeeding, secondary calving events will be altered due to viscous deformation. The three considered scenarios are detailed in Supplementary Note Surface lowering through viscous deformation will alter glacier surface slope and the 12. To determine the force required to halt ice-cliff failure, a synthetic mélange consisting of a plane of unbonded particles that are restricted from moving out of the domain is incorporated in the HiDEM simulations. The resulting depth-integrated force (N m−1) along the calving face is calculated from the strain asserted on the exposed particles at the glacier terminus. Incorporating synthetic mélange of varying thicknesses in our idealized simulations shows that the back force required to halt collapse ranges from 4.2 e6 to 5.7 e7 N m−1 , though counterintuitive, is explained by the minimal viscous deformation that is necessary to precondition the towering ice cliff for collapse. This allows the mélange to more efficiently counter the less-concentrated longitudinal stress at the waterline. These calculated mélange back force magnitudes are similar to those known to supress fracturing, calving and iceberg overturn at marine-terminating glaciers28  reduces bending stiffness more quickly (~W4) than tensile stiffness (~W2), and as beams bend, shear failure is induced in the glacier . HiDEMve is used here to assess how viscous deformation and brittle failure interact to form shear bands and influence the evolution of ice-cliff failure and glacier collapse via MICI. Because brittle failure occurs over a much shorter timescale than viscous deformation, the latter process is accelerated when it is incorporated in HiDEMve simulations. Ice-cliff deformation and failure thus do not interact on realistic timescales in HiDEMve, so it is also not possible to quantify TtF or Ĉ in these simulations. The HiDEMve simulations are valuable, however, as they provide insights into how viscous and brittle processes might interact and influence MICI. More information regarding HiDEMve is found in Methods.Once shear stresses increase so that a calving face enters the transition region between brittle and ductile deformationve simulations show a pattern of waterline bulging and forward lean similar to the terminus evolution seen in Elmer/Ice. However, pronounced shear bands emerge up-glacier of the calving front for the greatest terminus thicknesses, highlighting the importance of the interplay between shear fracture and viscous flow in MICI . Dense crevasse formation, calving via block rotation and slumping of the near-terminus ice surface is observed in simulations where basal slip is increased to match the low viscosity of HiDEMve. Failure of thinner domains (H ~ 880 m) is again dominated by vertical crevassing and block rotation, the crevassing being induced by tensile stress caused by stretching , which results in the rapid formation of a very dense mélange  is considered reasonable as the weight of the developed overhang also grows in proportion to H and Hc, further hastening failure. These differences indicate a qualitative transition in the dominant failure mode at a cliff height above which shear bands begin to form. A sharp decline in TtF is expected when this transition (Hc ~ 200 m) is reached. At the same time, the process generates a thick and dense mélange in front of the calving face, the height of which has been lowered by slumping action. This has the potential to stabilise the glacier terminus  is represented as a fitted power-law function that is based on Hc and dependent on Tice and B. Equation  and (2) the 660 m d−1 error between the retreat rate predicted by our parameterization in comparison to that associated with the run-away retreat, secondary calving event scenario  described in Supplementary Note Ĉ for these simulations correctly fall along the trendline of their respective temperature and basal slip scenario.The residuals of the fitted ice-cliff failure retreat rate parameterization are small for the lower-range of cliff heights that failed in our simulations Fig. , inset. 4. Our fitted retreat rate parameterization captures trends in retreat rates with increasing thickness, warming ice temperature and altered basal slip and the non-linear increase in Ĉ with increasing Hc. The latter relationship points to the potential for alarmingly rapid retreat and the initiation of run-away MICI retreat if viscous deformation and/or mélange buttressing do not counteract ice-cliff instability. It is imperative that the retreat rate parameterization proposed here be used in conjunction with model representation of ice surface lowering via dynamic thinning at a sufficiently high temporal resolution, which will determine whether the competing processes of ice flow and structural ice-cliff failure lead to either glacier stability or runaway MICI retreat.Although large model variance is apparent for some simulations of individual structural ice-cliff failure events, the presented retreat rate parameterization is a contribution to the ice-sheet modeling community that is concerned with adequately representing trends of retreatH to floatation for a given Hc will accelerate failure due to the increasing longitudinal stresses associated with the thicker glacier , ice fronts quickly reach states of rapid failure with increasing cliff heights. In all cases, ice-cliff failure produces copious mélange, either in the form of individual icebergs or, in the case of the visco-elastic model, a highly fractured mélange shelf. This mélange could provide sufficient resistance to suppress further calving, unless it can be evacuated away from the ice front. Therefore, the rate of mélange evacuation is a rate-limiting process for MICI, and will be influenced by the particular embayment or fjord geometry−1) in simulations of future Antarctic Ice Sheet retreat by DeConto and Pollard1. While we report lower values of Ĉ than DeConto and Pollard1 for 135 m < Hc < ~ 200 m, our reported values of Ĉ for greater cliff heights agree with previous assessments regarding the potential for more rapid ice-cliff failure retreat rates to be realised31. This is reasonable, as our retreat rates are relatively similar for the previously considered values of Hc (80–100 m)  investigate the influence of viscous deformation, brittle failure and shear-band formation on ice-cliff failure and MICI retreat, (b) derive an ice-cliff failure retreat rate parameterization and (c) quantify the magnitude of back force that is needed from mélange to suppress ice-cliff failure.15. We use a 4 km (long) × 3 km (wide) model domain with a surface slope of 0.021 and a retrograde bed slope of −0.018. These slopes are based on the setting of Thwaites Glacier, West Antarctica. Because it is impractical to model the entirely of the vast Thwaites Glacier calving front in HiDEM, we use passive sidewalls to represent conditions along the calving front that are not greatly influenced by lateral resistance from sidewalls. Noise is introduced to the basal surface to remove unphysical stress concentrations when Elmer/Ice output was transferred to HiDEMbe. All simulations are initialized with a linear bed friction law37:τb is basal shear stress, ub is the glacier sliding velocity and C is the friction coefficient20. As we are interested in exploring the parameter space in which structural failure of ice cliffs occurs, we do not allow the geometry to relax in our simulations; instead, we find the result of varying a number of input factors on the timing and magnitude of retreat associated with ice-cliff failure.The viscous deformation and advance of simulated glaciers are conducted with the open-source, full Stokes continuum glacier model, Elmer/Icebe. For this fast-deforming scenario, the difference in TtF was 1 h, which is within the temporal uncertainty associated with the majority of the model simulations run at a 6 h time step.Elmer/Ice runs are conducted with a 6 h time step. We test the sensitivity of our results to the Elmer/Ice time step by comparing the time to failure (TtF) for simulations of a 2500 m thick, −10 °C glacier run at 1 and 6 h time steps, TtF being the duration of time needed for viscous deformation to precondition the glacier to collapse via brittle failure in HiDEMbe)38. HiDEMbe replicates a wide range of calving styles19 and successfully reproduced observed calving events at Kronebreen, Svalbard22, Totten Ice Shelf, Antarctica21 and Bowdoin Glacier, Greenland20. The fracture properties used in this study are informed by those used to model Bowdoin Glacier20 and Store Glacier . Utilising HiDEMbe allows us to explicitly simulate fracture, avoiding assumptions of when and where calving occurs based on simulated stress fields in continuum ice flow models21.Brittle failure, after viscous deformation in Elmer/Ice, is simulated with the standard brittle-elastic implementation of the 3D Helsinki Discrete Element Model  to represent pre-existing micro-fractures within the ice21  effectively enhances fracture toughness and discourages shear localisation and damage at the stresses induced in our HiDEMbe to test for cliff failure. This workflow allows us to consider the contrasting fluid and brittle-solid characteristics of ice22. Key model parameters are included in Table be at varying time-steps of a given simulation to determine the TtF. The associated retreat magnitude is measured in Paraview (v. 5.5.0).Evolved Elmer/Ice glacier geometries are exported to HiDEMH) (with a corresponding cliff height (Hc)), ice temperature (Tice) and basal friction (B). Grounded glaciers with H = 1000, 1500, 2000 and 2500 m are tested for cliff failure over 50 d of viscous deformation occurring at Tice = −20, −10 and −5 °C. Extra simulations are conducted between H = 650 and 950 m to determine the thickness, within 50 m, at which cliff failure initiates for a grounded glacier. These simulations are considered as normal (Bn) with a slip coefficient prescribed in Elmer/Ice that decreases as a linear function from 1.0e2 to 1.0e4 m a−1 MPa−1 along the 4 km model domain and a surface-to-base velocity ratio of 2.6 for H = 1500 m. Inflow velocity was set at 1500 m year−1, so basal slip and inflow are broadly similar. This initialization results in velocity values of ~1.5–2 km year−1 up-glacier of the calving front. To assess how surface lowering through viscous deformation will impact subsequent calving events, test simulations of the succeeding calving event after the initial cliff failure are run for H = 1000 (Tice = −5 °C) and 2000 m (−5 and −20 °C). For these simulations, Elmer/Ice is initialized with the surface slope and Hc of the new calving face after the first calving event simulated in HiDEMbe. Evolved geometries are again transferred from Elmer/Ice to HiDEMbe to test for failure.A series of simulations are run to test how TtF and retreat magnitude are influenced by glacier thickness (Bh) results in a low surface-to-base velocity ratio  and accelerated overhang development, as basal advance is more similar to advance of the glacier surface. Decreasing slip so that the bed approaches a frozen condition (Bf) results in simulation conditions where the surface-to-base velocity ratio is high (5.7 for H = 1500 m) and the overhang development is slowed, as surface advance outpaces that of the glacier base. The inflow velocity was adjusted to 1250 and 1750 m year−1, for simulations with Bh and Bf conditions. Tice remained static at −20 °C for these simulations, this temperature representing Tice at Thwaites Glacier in the vicinity of the waterline where longitudinal deviatoric and shear stresses concentrate39.To test the impact of varying basal slip on the timing and magnitude of cliff failure, simulations were conducted over the above range of thicknesses with the basal slip coefficient decreased and increased by an order of magnitude. Increasing basal slip conditions  impacts HiDEMbe tensile and shear strength. Test cases were run for Tice = −5 °C and H = 1000, 1500 and 2000 m to demonstrate how weakening shear strength, relative to tensile strength, influences failure. Tests are run with W = 0.55, 0.4 and 0.3. The default setting for W is 0.7, this being a non-dimensional relation between particle diameter and beam width. This parameter assignment has been validated in simulations of calving at marine-terminating glaciers in and Svalbard25 and Greenland20 ).The width of inter-particle cylindrical beams  and TtF for the viscoelastic cases. We therefore use kinetic energy as a measure for ice-cliff failure activity. We hypothesise that, as calving and fracture begin, the acceleration of kinetic energy can be described by a single scaling function of time, g(t). The dependence of the kinetic energy on glacier thickness (SCL) and basal friction (f) can then be described by rescaling time and energy: e, and SCLt are functions of SCL.When basal friction is scaled down in the viscoelastic simulations to match the low viscosity of HiDEMĈ and Hc. A power-law equation (y = Ixα) using the common logarithm  is fit for this relationship for the results of the Tice = −5, −10 and −20 °C series of simulations for Bn. Fits are also derived for Bf and Bh for Tice = 20 °C. We report the fitted values of I and α in Eq. (Log-log plots are used to determine if a power-law relationship existed between Supplementary InformationPeer Review FileSupplementaryMovie_1Description of additional supplementary files