In order to solve issues related to bridge girders, expansion devices and road surfaces, as well as other structures that are prone to fatigue failure, a kind of fatigue-resistant elastic polyurethane concrete (EPUC) was obtained by adding waste rubber particles (40 mesh with 10% fine aggregate volume replacement rate) to conventional engineering polyurethane concrete (PUC). Based on the preparation and properties of EPUC, its constitutive relation was proposed through compression and tensile tests; then, a scanning electron microscope (SEM), an atomic force microscope (AFM) and a 3D non-contact surface profilometer were used to study the failure morphology and micromechanisms of EPUC. On this basis, four-point bending fatigue tests of EPUC were carried out at different temperature levels  and different strain levels (400 με~1200 με). These were used to analyze the stiffness modulus, hysteresis angle and dissipated energy of EPUC, and our results outline the fatigue life prediction models of EPUC at different temperatures. The results show that the addition of rubber particles fills the interior of EPUC with tiny elastic structures and effectively optimizes the interface bonding between aggregate and polyurethane. In addition, EPUC has good mechanical properties and excellent fatigue resistance; the fatigue life of EPUC at a room temperature of 600 με can grow by more than two million times, and it also has a longer service life and reduced disease frequency, as well as fewer maintenance requirements. This paper will provide a theoretical and design basis for the fatigue resistance design and engineering application of building materials. Meanwhile, the new EPUC material has broad application potential in terms of roads, bridges and green buildings. Due to rapid developments in the global economy, significant increases in traffic pressure and changes in inclement weather conditions, roads and bridges have become more prone to fatigue damage. Conventional materials such as concrete are characterized by high stiffness, and they will struggle to resist the large deformations brought about by impact loads in the future. As such, it vital that we find an elastic material with a short maintenance time, light weight, high strength, a strong cohesive force and excellent structural integrity for application in the field of road and bridge construction and repair. Importantly, the annual number of scrap tires has reached 1.5 billion globally. Like plastic products, waste tires are difficult to degrade and do not disappear naturally after being buried underground for decades, causing a phenomenon known as “black pollution”. Therefore, the effective recovery and reuse of waste rubber to reduce environmental pollution can make important contributions to the construction of an eco-friendly society ,3. At thRubber concrete and polyurethane concrete have attracted many researchers because of their excellent physical and mechanical properties. Rubber concrete can effectively improve the elastic deformation capacity of concrete, as well as its heat insulation, frost resistance, shock absorption and sound insulation effects. Eldin and Senouci, as well as Khatib et al. ,6, selecIn this study, we combine the excellent properties of rubberized concrete and conventional PUC materials to systematically study the preparation, mechanics and fatigue properties of EPUC. We hope that the findings from this process can effectively solve the problem of fatigue damage in building materials as it currently stands. As such, we provide a means by which to effectively recover and reuse waste rubber, reduce environmental pollution and make an important contribution to the construction of an eco-friendly society. Moreover, our study has significant potential regarding its application in the reinforcement and repair of existing structures and green buildings.Polyphenylene isocyanate  was purchased from Beste Chemical Technology Co. Ltd., Dalian, China. Combined polyether  was purchased from Jiangsu Hai’An Petrochemical Co. Ltd., Haian, China. The catalyst (phosphoric acid) was purchased from Shandong Yisheng Polyurethane Co. Ltd., Jinan, China. Portland cement (average particle size = 1.455 μm) was purchased from Harbin Honggu Cement Manufacturing Co. Ltd., Harbin, China. Rubber particles  were made by grinding used rubber tires. Aggregate gradation adopted AC-10 fine-grained concrete typical gradation, and the specific particle size and ratio are shown in The preparation process of EPUC improved on the basis of previous studies, and it is shown in (1) Compression test: The cube compressive strength test of EPUC was carried out at a room temperature of 20 °C, and the size of the sample was a standard cube of 100 mm × 100 mm × 100 mm . Figure The compressive strength of EPUC is calculated as follows:F—ultimate load (N);A—compression area (mm2).(2) Straight-tension test: In order to eliminate the uncertain influence of a single specimen, six sets of parallel specimens (ZL01~ZL06) were selected for the straight-pull test. A dumbbell-type sheet was used as the standard specimen  of the sBased on the research results for the SHRPA-003A Strategic Highway , and in The fatigue test instrument in this paper was a UTM-30 fatigue-loading test system  with a limit load of 30 kN UTM-30 . Three t6 times and still failed to meet the above conditions, the test was stopped, and the fatigue life of the specimen under these conditions was deemed to be infinite.The main parameters such as loading frequency, loading waveform and strain level need to be calibrated before the four-point bending fatigue test, as different parameter choices will greatly affect the fatigue life of EPUC. In this paper, a loading frequency of 10 Hz and a continuous uninterrupted semi-positive vector wave were selected for the fatigue test ; the strL = the span of bending specimen (m);The maximum tensile stress (P = the peak load (N); h = the height of the bending specimen;a = the intermediate spacing between adjacent collets (m).S = modulus of bending stiffness (Pa)The stiffness modulus is calculated according to Equation (4), the lag Angle is calculated according to Equation (5), the dissipated energy within the unit load cycle is calculated according to Equation (6) and the cumulative dissipated energy is calculated according to Equation (7).f = loading frequency (Hz);t = time of hysteresis deformation (s).3).3);3).2) and 3D non-contact surface profilometry were used to investigate the surface morphology and roughness .A scanning electron microscope  was used to observe the surface and section morphology of EPUC with the optimal ratio. Atomic force microscopy  Compression properties3 and the average compressive strength is 59.7 MPa. By comparison, it is found that, while EPUC meets the strength level of C50 concrete, its density is only 70% [In order to eliminate the uncertain influence of a single specimen, six sets of parallel specimens (F01~F06) were selected to test compressive strength and density. The compressive strength of EPUC is shown in only 70% .The average compressive strength of the six groups of specimens was taken to draw the stress–strain curve, as shown in The mechanical properties of EPUC are similar to ordinary concrete, and the compression process can be divided into the following two stages. First is the elastic stage , where the stress–strain curve of the specimen at the initial stage of loading is in positive linear correlation. The maximum compressive strength at this stage is 53.26 MPa, which is defined as the elastic limit of the material, and the strain at this stage is 25,387.33 με. Second is the yield stage , where the stress–strain curve of the specimen at the late loading period is approximately a downward parabolic curve with an ultimate compressive stress of 59.7 MPa and a failure strain of 35,665.72 με. After removing the fluctuation value of the initial test (the microstrain is between 0–3500 με), the stress–strain curves of the remaining two stages are fitted. The fitting equations of the two stages are as follows:Eε), stress and strain in elastic compression stage are proportional. E is the slope of the straight-line segment in E = 2550.88 MPa); this value is much lower than the elastic modulus of ordinary concrete, which indicates that EPUC has excellent elastic deformation ability.According to Hooke’s law of tension and compression Tensile propertiesThe tensile strength of six groups of parallel specimens (ZL01~ZL06) is shown in By fitting the stress and strain data of straight-tension specimens, the straight-tension stress–strain curve of EPUC is obtained. It can be seen from (1)Microscopic morphology analysisAs can be seen in (2)Failure mode analysisThree groups of specimens with different bone–glue ratios (ST-1~ST9) were selected for analysis to explore the influence of bone–cement ratio on the compressive failure morphology of EPUC. The axial compressive failure morphology of ST-1~ST-9 is shown in ST1~ST6 is EPUC with a 10~15% bone–glue ratio. It has low strength and its failure pattern is irregular. The inside of the specimen is relatively loose, and various constituent materials do not play a full role. For specimens with a 20% bone–glue ratio of ST7~ST9, their failure mode is a typical X-type failure mode. Compared with ordinary concrete, there is no brittle crack or splitting damage, and only some small cracks exist; the morphological integrity of the damaged specimens is therefore intact. With the addition of rubber particles, the EPUC is filled with tiny elastic structures, and the interface bonding between aggregate and polyurethane is effectively optimized. The rubber particles evenly distributed in the concrete use their own elastic absorption of impact energy; they also slow down the internal impact of micro-cracks and significantly enhance the elastic deformation ability of EPUC so as to effectively slow down the further expansion of micro-cracks in the concrete and accelerate the destruction process of the structure.The bone–glue ratio greatly affects the compressive strength of EPUC. When the bone–binder ratio content is low, there is a large gap between aggregates, and the bonding force between polyurethane cementing materials is weak. Rubber particles do not fully function, forming tiny “holes” in the concrete with no carrying capacity, resulting in a significant reduction in overall strength. The best bone–glue ratio is 20%, and polyurethane elastomer can completely wrap the aggregate, thus rendering the whole specimen uniform and smooth and negating the need for vibration compaction. Continuously increasing the bone–glue ratio has no obvious effect on strength, and it increases the difficulty of controlling water content during the test, thus affecting the forming state of EPUC.(1)Analysis of bending stiffness modulusThe bending stiffness modulus formula is shown in Equation (4).5 times before the fatigue cycle begins a slow linear downward trend; at this stage in the accumulation of fatigue damage, there are tiny cracks in the elastic polyurethane and concrete, but their mechanical properties are still considered at a high level. In the second stage, the accumulated damage to EPUC reaches a certain range after 100,000 fatigue cycles, and the bending stiffness modulus rapidly decays to less than 50% of the initial modulus in terms of bending tensile strength; this indicates that the material has fatigue damage. Both the low temperature and the high strain advance the second stage decay of the modulus in relation to bending stiffness.From (2)Analysis of initial stiffness modulusThe initial stiffness modulus of EPUC is an important characteristic of its fatigue curve and an important index to evaluate the fatigue life of EPUC. The initial stiffness modulus of EPUC fluctuates significantly. In order to eliminate the influence of unstable data in the early stage of the test, at least according to the AASHTO TP8 specification, the initial stiffness modulus of this test is the value of the rigidity modulus after the 50th fatigue cycle. The test results are shown in At the same temperature, the initial stiffness modulus of EPUC decreases with the increase in strain. Softening at high temperature and hardening at low temperature at the same strain causes the initial stiffness modulus to decrease with the increase in temperature, but it is easy to advance the brittle failure time of specimens and shorten their fatigue life.(3)Analysis of lag AngleThe lag angle is an important index for evaluating the viscoelastic and fatigue resistance properties of materials. The smaller the lag angle, the more elastic the material property tends to be; otherwise, it tends to be viscous. The lag angle in this paper is calculated according to Equation (5). EPUC is a kind of viscoelastic material with a hysteresis angle between 0~90°. The higher the temperature, the higher the lag angle. This is because polyurethane material is a kind of heat-resistant cementifying material that displays high temperature softening behavior, in the same manner as asphalt, and its hardness decreases with the increase in temperature. At −20 °C, the lag angle of EPUC is less than 10, which is a perfect elastic material with good adaptability to the anchorage area of expansion joints in cold areas. At the same temperature, the lag angle of EPUC is proportional to the fatigue strain level, and the lag angle proves the ability of EPUC to resist fatigue failure from the side. The relationship between the hysteresis angle and the number of fatigue actions is an approximate downward parabola; the higher the strain level, the steeper the curve. It can be seen from (4)Analysis of dissipated energyDissipated energy is the energy required by a material to resist external fatigue load. Under fatigue load, deflection and reorganization will occur inside the structure; important in this regard is the movement of aggregates such as sand and gravel, and the generation of new surfaces. The dissipated energy in a single load cycle is calculated according to Equation (6) and the cumulative dissipated energy is calculated by Equation (7). The variation trend in dissipated energy with fatigue times is shown in 3 at −20 °C and 1200 με. The change in dissipated energy presents the following two-stage change trend. At the beginning of the fatigue cycle, the dissipated energy decreases rapidly due to the change in the internal structure of the material. When the number of cycles reaches more than 100,000, the dissipated energy gradually stabilizes and steadily decreases within a certain range.The analysis shows that the energy consumption of EPUC decreases with an increase in loading times. The higher the strain level at the same temperature, the greater the energy consumed by the internal recombination of EPUC to resist external deformation. With the increase in temperature, the material tends to be viscous, and the dissipated energy at the same strain level decreases accordingly. The maximum dissipation energy is 0.95 kJ/m(5)Fatigue equation of EPUCN and strain level ε of EPUC at different temperatures are fitted logarithmically, and the results are shown in The fatigue life σ = E ε—the ε-N fatigue equation is transformed into a classical S-N fatigue equation, as shown in According to the expression of Hooke’s law—We compared EPUC to the PUC fatigue equation proposed by Gao Hongshuai  and drewS-N curve of the fatigue life of EPUC under the coupling actions of temperature and external force. Our findings are as follows:In this study, the preparation of EPUC and its mechanical properties was examined. We used a four-point bending fatigue test to present the (1) The best mixture ratio for EPUC is a cement-to-bone ratio of 20% and 40 mesh rubber particles mixed with a 10% fine aggregate volume substitution ratio. The specimen had an exemplary failure mode and considerable integrity, and only a few small cracks were apparent. In addition, the micro-morphology analysis results show that the rubber particles were evenly distributed in the EPUC and bonded well with the polyurethane material, which effectively guaranteed the strength of the elastic polyurethane concrete and showed that EPUC had a reliable enough surface roughness to meet road performance.(2) The results of mechanical tests showed that the elastic limit of EPUC was 53.26 MPa and the maximum elastic strain was 25,387.33 με. The ultimate tensile stress was 41.1 MPa and the maximum tensile strain was 14,436.47 με. These results demonstrate that EPUC has excellent mechanical properties that are even better than general C50 concrete.(3) At room temperature and low strain level, EPC has outstanding fatigue properties. The higher the strain level, the shorter the fatigue life of elastic polyurethane concrete; the fatigue life of EPUC at 400 με could grow by more than two million times. Taking 20 °C as the benchmark, it is clear that the lower the temperature, the shorter the fatigue life of EPUC. Therefore, adverse climatic conditions in cold areas will have an adverse effect on its application, but its fatigue life is still better than that of ordinary building materials.


An expanding group of autoimmune diseases is now recognized to be hallmarked by pathogenic IgG4 autoantibodies. IgG4 has the unique ability to exchange Fab-arms, rendering it bispecific and functionally monovalent. Here we show that autoantibody functional monovalency significantly amplifies the pathogenicity of IgG4 autoantibodies using patient-derived monoclonal antibodies in an in vivo model of MuSK myasthenia gravis. Therefore, subclass switching to predominant IgG4 autoantibodies is a critical step in the development of MuSK myasthenia gravis. This new mechanism in autoimmunity is also potentially relevant to 29 other IgG4-mediated autoimmune diseases known to date, allergy and other disease settings where IgG4 antibodies contribute to pathology. Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders. Recently, a growing class of antibody-mediated autoimmune diseases characterized by predominant pathogenic immunoglobulin (Ig) G4 responses has been described –4. IgG4 Myasthenia gravis (MG) with antibodies against muscle-specific kinase (MuSK) is one of the first recognized IgG4-mediated autoimmune diseases. MuSK autoantibodies are predominantly of the IgG4 subclass, although anti-MuSK IgG1 and IgG3 may be present concurrently at lower titers . Anti-Mu121721To investigate the role of MuSK antibody valency on their pathogenicity in vivo, pure and stable bispecific MuSK antibodies are needed. Remaining monospecific MuSK antibodies may have confounding effects, e.g., by competing for binding with MuSK and thereby masking effects of the bispecific MuSK antibodies. We therefore adapted the controlled Fab-arm exchange (cFAE) method to IgG4 , 25. In SI Appendix, Fig. S1). The purity of the separated fractions was confirmed with MS  anti-MuSK antibodies were determined with capillary electrophoresis (CE) hyphenated with mass spectrometry (MS) . The mon with MS D. The ef with MS B.SI Appendix, Fig. S2A). The in vivo half-life ranged between 38 and 63 h and varied by antibody . To ensure continuous in vivo exposure, an injection regimen of every 3 to 4 d was chosen for the passive transfer experiments. The minimum dose required to induce progressive phenotypical myasthenic symptoms was determined with monovalent 11–3F6xb12 IgG4. A dose of 2.5 mg/kg every 3 to 4 d resulted in progressive muscle weakness starting after about 5 d, leading to 20% body weight loss after 11 d . No clinical myasthenic muscle weakness or weight loss was observed at the 1.25 mg/kg dose. The serum antibody levels in these latter mice were approximately 10-fold lower compared with the 2.5 mg/kg regimen, indicating at these lower doses the pharmacokinetics do not change linearly . To compare the pathogenicity of monovalent vs. bivalent MuSK antibodies, we injected the bivalent or monovalent MuSK antibodies or the b12 control at 2.5 mg/kg every 3 d . The mice lost nearly all their grip strength and showed progressive fatigable muscle weakness in the inverted mesh test, starting within 1 wk .Both monovalent anti-MuSK IgG4s induced rapid and severe myasthenic muscle weakness and body weight loss  on the left calf muscles was performed on the final day of the experiment. Decrement of the compound muscle action potential (CMAP) is a clinical electrophysiological hallmark of MG and is caused by loss of transmission in a progressive number of NMJs during the stimulations . Both moSI Appendix, Fig. S4A), indicating individual differences in pharmacokinetics. Specifically, serum levels of the b12 antibody were lower compared with the different anti-MuSK clones, despite identical dosing. The levels of the MuSK antibodies were quite comparable, except at the final stage of the experiment, where titers of the bivalent IgG4s plateaued, while the monovalent anti-MuSK IgG4 serum levels continued to rise. Possible explanations could be the body weight and volume loss which mice injected with monovalent MuSK antibodies experienced at this stage or the kinetic differences between monovalent and bivalent MuSK antibodies due to receptor-mediated internalization and degradation.To monitor in vivo exposure to the antibodies, serum samples were taken before the first injection and 2 d after every following injection. Serum titers varied between individual mice . The only modification observed was the in vivo removal of C-terminal lysine for 11–3F6 and 11–3F6xb12 . C-terminal lysine clipping of IgGs is a well-known natural process, which does not affect antigen-binding ability . The parental b12 control antibody therefore seems to be cleared slightly faster, but this is unlikely to have had an effect on the model as such. No other species or degradation products could be detected, indicating that the antibodies remained stable in vivo and ruling out confounding effects, such as disassembly of bivalent MuSK antibodies.To confirm that the IgG4s were stable in vivo, serum was collected at the final day of the experiment and analyzed with CE-MS. All five antibodies were successfully retrieved from the circulation and found to be intact at the end of the experiment  anti-MuSK IgG4s makes them much more pathogenic than their monospecific equivalents with functional bivalency for MuSK.To further characterize muscle function, the contraction force upon repetitive nerve stimulation was examined on the left hemidiaphragm ex vivo. Of note, functional effects on the diaphragm may be larger compared with other muscles because it is directly exposed to the antibodies upon intraperitoneal (i.p.) injection. Stimulation of the phrenic nerve at 40 Hz for 7 s resulted in tetanic contraction. Quantification of the area under the curve revealed similar patterns between groups as seen with the CMAP decrement in the calf muscles. The monovalent MuSK antibodies reduced the contraction force most severely H. BaseliP = 0.079). Diaphragms of mice exposed to bivalent 13–3B5 were affected by 125 nM dTC, indicating that although the clinical phenotype caused by 13–3B5 is mild, the NMJs already have substantial loss of AChR and are in a state of subclinical myasthenia . In the b12 control group, the tetanic contraction force of the diaphragm was not reduced by 125 nM dTC, indicating a healthy safety factor I. Both masthenia I. Taken SI Appendix, Fig. S6 A and D). Quantification of the total AChR signal per NMJ revealed that both monovalent anti-MuSK IgG4s and the bivalent 13–3B5 caused a strong reduction of AChRs, while mice exposed to bivalent 11–3F6 had more remaining AChRs compared with monovalent 11–3F6xb12 and bivalent 13–3B5 . The intensity and morphology of the presynaptic SV2 signal were not affected by exposure to these mono- and bivalent anti-MuSK IgG4s . Denervation assessed by the colocalization of the presynaptic SV2 signal with the postsynaptic AChR signal revealed a similar pattern as seen with the postsynaptic AChR signal . Overall, these data suggest that postsynaptic pathology of the NMJ is the main cause of the neuromuscular dysfunction induced by these MuSK antibodies and that loss of AChR area results in less alignment with the presynapse.Loss of appropriate pre- and postsynaptic alignment is also known to contribute to the NMJ dysfunction seen in MG animal models , 10, 17.SI Appendix, Fig. S7 B–D for individual traces). Grip strength slowly declined over a period of a week to a near complete loss on the final days of the experiment . Finally, exposure to bivalent 13–3B5 resulted in a significant CMAP decrement compared with both the control group and bivalent 11–3F6 . The differential effects between 13–3B5 and 11–3F6 therefore confirm that bivalent MuSK antibodies can be pathogenic, but their pathogenic potential is antibody dependent.Mice exposed to bivalent 11–3F6 did not show signs of myasthenic muscle weakness on any of the in vivo parameters at higher dose and after prolonged exposure B–E. To d2), which are considered most mature and therefore relevant . In summary, monovalent MuSK IgG4 abolished agrin-Lrp4-MuSK signaling in vitro, whereas bivalent anti-MuSK IgG4 partially activated this signaling, independent of agrin.C2C12 myotubes contain all the muscle-specific machinery to interrogate the agrin-Lrp4-MuSK-signaling cascade in vitro, except for neural agrin. Addition of agrin to these cultures activates this cascade, leading to MuSK phosphorylation and AChR clustering –40. Monorelevant . HoweverIn this study, we demonstrate a new disease mechanism in autoimmunity related to the unique feature of IgG4 to undergo Fab-arm exchange. We provide evidence that autoantibody functional monovalency for MuSK amplifies the in vivo pathogenicity of IgG4 MuSK antibodies. Mechanistically, this may be explained by the respective antagonistic vs. agonistic effects of the Fab-arm exchanged monovalent and parental bivalent IgG4 antibodies on the MuSK-signaling cascade. The sequence of events driving IgG4 autoantibody pathogenicity and the main conclusions of this study are summarized in IgG4 is the only human antibody subclass able to undergo Fab-arm exchange under physiological conditions . It furtMonovalent anti-MuSK IgG4s inhibited agrin-Lrp4-MuSK signaling in vitro and induced progressive myasthenic weakness and NMJ morphological abnormalities in NOD/SCID mice similar to polyclonal patient-purified IgG4 and monovalent Fab fragments , 23, 45.Patient-derived bivalent MuSK antibodies can potentially be pathogenic in vivo, but this differed considerably between the two antibodies studied here. The bivalent parent antibody 13–3B5 was able to cause overt myasthenic symptoms, but this required more time to start (2 to 3 wk) and progressed more slowly, as compared with monovalent 13–3B5xb12. This time course of myasthenic symptom development and progression resembles what has been reported in MuSK active immunization models , 46, 47.The bivalent 11–3F6 parent antibody did not induce any signs of clinical myasthenic muscle weakness, not even when doubling the exposure time and increasing the dose. Subtly different epitopes may differentially affect the conformation and activation of MuSK and, thereby, the subsequent downstream signaling and pathogenicity of bivalent MuSK antibodies. Whether nonpathogenic MuSK antibodies such as 11–3F6 or #13  can mitiIt is important to note that a polyclonal pool of MuSK antibodies exists in patients. The question arises as to how representative the investigated clones are for the polyclonal response in different MuSK MG patients, which warrants further research. However, because the clones bind the main immunogenic region of MuSK at two different epitopes within this region , 15, 16,A critical step in this study was the generation of stable bispecific  IgG4 antibodies. The cFAE method presented here broadens the toolbox available for generating therapeutic bispecific antibodies. By altering three residues in the Fc tail of IgG4 and adding excess of an irrelevant donor antibody (b12), <1% monospecific antibody contamination could be achieved. Furthermore, these bispecific IgG4s were stable after intraperitoneal injection in NOD/SCID mice. The field of bispecific antibody therapeutics has taken an exponential flight . The the52Taken together, IgG4 Fab-arm exchange is not an innocent bystander activity, but instead potentiates the pathogenicity of MuSK autoantibodies. This may be relevant for the growing number of IgG4-mediated autoimmune diseases and other disease settings where IgG4 plays a pathogenic role, such as where IgG4 blocks endogenous antitumor responses in melanoma patients , 56.Anti-MuSK clones 11–3F6 and 13–3B5 were previously isolated from a MuSK MG patient and produced with a human IgG4 Fc . The S22SI Appendix, SI Materials and Methods). To generate monovalent MuSK antibodies, each of the anti-MuSK clones was combined with 1.3 to 1.4x molar excess of the b12 antibody and 75 mM 2-mercaptoethylamine-HCl (Sigma-Aldrich) for 5 h at 31 °C .Recombinant monoclonal antibodies were produced in suspension FreeStyle HEK293-F cells as described previously  or usingat 31 °C . PreparaSI Appendix, Table S1). Furthermore, antigen-binding capacity was assessed using MuSK or gp120 enzyme-linked immunosorbent assay (ELISA) . Antibody integrity was confirmed using PageBlue Coomassie stain according to the manufacturer’s instructions (Thermo Fisher).Concentrations of all recombinant antibodies were determined with nanodrop  using specific extinction coefficients predicted with the ProtPI tool based on the amino acid sequences  or purchased from Charles River Laboratories. They were housed in sterile, individually ventilated cages and provided with sterile food and drinking water ad libitum. Female mice were aged 8 to 10 wk at the start of the experiment unless otherwise specified.SI Appendix, SI Materials and Methods). To compare pathogenicity of monovalent and bivalent MuSK antibodies, mice were i.p. injected with 2.5 mg/kg recombinant antibody every 3 d. Mice were allocated to a treatment group by a laboratory member not involved in the experiment. Serum samples were taken on day 6 and 2 d after every injection. Body weight, in vivo muscle strength, and endurance were assessed daily. On day 11, mice were subjected to the end-point analyses described below.The experimenters were blinded for the injected antibodies throughout all experiments and analyses  were combined with the two animals that received the b12 control used as a healthy reference for EMG and contraction measurements.Over all experiments, one mouse injected with 2.5 mg/kg 13–3B5 had to be excluded for all parameters because the serum titers revealed lower antibody levels on two time points in the experiment, likely due to misplacement of i.p. injections. For a further three mice , the measurements on the inverted mesh had to be excluded because the animals did not complete 180 s hanging during the training period.2 inhalation. During dissection more blood was collected via vena cava puncture. The serum from the tail and vena cava was pooled and stored at –20 °C until further analysis. The right hemidiaphragm and ETA were dissected for NMJ morphological analyses described below.After the daily measurements on the end-point day, mice were subjected to repetitive nerve stimulation EMG of the calf muscles under anesthesia, described in detail previously . One of To measure ex vivo contraction force, the left phrenic-nerve hemidiaphragm was prepared as described previously . BrieflyThe most dorsal strip of the right hemidiaphragm and the whole ETA were pinned up in Sylgard lined dishes and fixed in 1% paraformaldehyde (PFA) in PBS for 30 min. All incubations were done at room temperature unless otherwise specified. To enable parallel processing of all muscles in an experiment, they were stored floating in 1% PFA at 4 °C for 3 to 7 d. Before staining, muscles were blinded to the phenotypes observed in the experiment until all morphology analyses were completed. The tissues were extensively washed with PBS, remaining 1% PFA was neutralized with 0.1 M glycine in PBS (1 h), and muscles were blocked with 2% bovine serum albumin  and 1% Triton-X (Sigma) in PBS (2 h). The muscles were subsequently incubated with 0.2 µg/mL mouse anti-SV2  in block overnight at 4 °C. After 6x 10 min washes with PBS, tissue was incubated with 2 µg/mL BTX-488 to visualize AChRs and 2 µg/mL Alexa Fluor 594-conjugated donkey anti-mouse IgG  in 2% BSA in PBS for 2 h. After 6x 10 min washes in PBS, muscles were mounted in Prolong Gold mounting medium (Thermo Fisher) and stored at 4 °C until imaging. Due to technical issues with the staining, two ETA muscles (both in the b12 group) and two diaphragm preparations (1x in b12 group and 1x in 13–3B5xb12 group) had to be excluded from further analysis. Consequently, for the ETA muscles, the b12 control group was left with only two independent data points. Therefore, statistical analysis was not done on this dataset.n = 1 for visualization and further analysis. NMJ colocalization analysis was conducted on the ETA muscles .One high-resolution Z-stack of a representative part of the muscle was taken using a 20x objective on a SP8 confocal laser-scanning microscope with Las X software (Leica). Z-stacks were converted into maximum projections and further analyzed using ImageJ 1.52n. For the diaphragm images, 20 en face NMJs were randomly selected in the 488-BTX channel and analyzed for intensity and area using a manual threshold. For the analysis of the ETA, 30 enface NMJs were selected to better capture the variation seen in these preparations. A global threshold was manually determined for the diaphragm and ETA separately. The total AChR signal (intensity X area in the 488-BTX channel) of all analyzed NMJs per image were averaged and used as an 2) and all clusters >3 µm2 were analyzed separately. Both assays were performed in triplicate.C2C12 myoblasts were obtained from CLS Cell Lines Service, tested for mycoplasma contamination, and maintained for a maximum of seven passages after thawing. MuSK phosphorylation and AChR clustering were assessed as described previously . Brieflyt test. Measurements from the end-point day was used for statistical analysis by GraphPad Prism (version 8.1.1). Differences were considered significant at P < 0.05.Data are expressed as mean ± SEM. Comparisons among three or five groups were analyzed using one-way ANOVA with Šidák-corrected comparisons for parametric data. Hanging time (nonparametric data) was analyzed with the Kruskal–Wallis test with Šidák-corrected comparisons. The following comparisons were predefined: b12 vs. 13–3B5, b12 vs. 13–3B5xb12, b12 vs. 11–3F6, b12 vs. 11–3F6xb12, 13–3B5 vs. 13–3B5xb12, 11–3F6 vs. 11–3F6xb12, 13–3B5 vs. 11–3F6, and 13–3B5xb12 vs. 11–3F6xb12. Comparisons between two groups were analyzed using two-tailed unpaired All animal studies were euthanized with approval of the Dutch national and local animal experiments committees, according to Dutch law and Leiden University guidelines.Supplementary File


BackgroundIrrational prescriptions have an ill effect on health as well as on healthcare expenditure. Prescription auditing is an important tool to improve the quality of prescriptions, which in turn improves the quality of health care provided. Regular and timely audits of antibiotic prescriptions can prevent irrational antibiotic usage.IntroductionThe inappropriate use of drugs is a global health problem, especially in developing countries like India. In 2015, during the 68th World Health Organization (WHO) Regional Committee for Southeast Asia, all Member States of the region, including India, endorsed the “Regional Strategy for Patient Safety in the WHO Southeast Asia Region (2016-2025)” aiming to support the development of national quality of care and patient safety strategies, policies, and plans and commit to translating those objectives of the Regional Strategy into actionable strategies at country level.MethodologyA retrospective observational study was conducted in a 330-bedded, National Accreditation Board for Hospitals & Healthcare Providers (NABH)-accredited tertiary healthcare center. The study period was six months, from January 2019 to June 2019.ResultsNinety-five point four-five percent (95.45%) of the doctors attended the sensitization program and all accepted following the standard prescribing protocols. Sixty-nine point seven percent (69.7%) of the doctors were aware of the availability of drugs in the hospital pharmacy stores. Seventy-four point two-four percent (74.24%) of the doctors were aware of the ongoing prescription audits. Seventy-two point two-seven percent (72.27%) of the treating doctors were of the opinion of selecting the appropriate antibiotics based on hospital antibiogram. The importance of antibiograms from cultures and environmental surveillance was followed well only after sensitizing all the treating doctors. Ninety-five point four-five percent (95.45%) of the doctors were of the opinion of taking the permission of a higher authority to start high-end antibiotics. Seventy-seven point one-zero percent (77.10%) doctors recommended sample collection prior to antibiotic administration. Sixty-three percent (63%) of the patient’s clinical condition improved with the antibiotics prescribed prior to the culture report.ConclusionBy judicious use of antibiotics, we can reduce the evolution of antibiotic resistance in bacteria and extend the useful life of antibiotics that are still effective. Antibiotic use patterns must be studied to address complications resulting from a large number of antibiotics. Irrational prescriptions have an ill effect on health as well as on healthcare expenditure. Prescription auditing is an important tool to improve the quality of prescriptions, which in turn improves the quality of health care provided. Regular and timely audits of antibiotic prescriptions can prevent irrational antibiotic usage. Microbiologists practicing the reporting of minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBC) find that they are excellent predictors of the potency of an antimicrobial against the infecting organism, but they provide essentially no information on the time course of antimicrobial activity. MIC provides no information on growth inhibitory effects that may persist after antimicrobial exposure. Hence, it mandates a follow-up regarding the ongoing treatment and response to the treatment without recurrence of symptoms and with minimal side effects.The inappropriate use of drugs is a global health problem, especially in developing countries like India. Health care systems in India are divided into public and private sectors; treatment in the private sector is much more expensive than in the public sector . DispensIn India, health expenditure accounts for around 1.4% of the gross domestic product (GDP). In India, there are public and private healthcare systems; private-sector treatment is significantly more expensive than public-sector treatment. The Pharmacy Act of 1948 governs the dispensing of pharmaceuticals in India, where only licensed pharmacists and physicians are permitted to distribute medicine to patients. In 2017, India released its National Action Plan to Combat AMR (NAPAMR), which was in accordance with the worldwide action plan to combat AMR. Antibiotic policies are frequently implemented as part of an antibiotic stewardship program to reduce needless antibiotic usage and improve management. It is necessary to evaluate data on antibiotic prescription trends in patients in order to establish such a policy for infection management. Self-medication with antibiotics is common in India and the prevalence ranges between 16% and 85% in medical students [A retrospective observational study was conducted in a 330-bedded National Accreditation Board for Hospitals & Healthcare Providers (NABH)-accredited tertiary healthcare center. The study period was six months, from January 2019 to June 2019.The aim of this audit was to determine the effect of the awareness of good prescribing practices; evaluate adherence to antibiotic policy; and promote documentation of adverse events.Audit criteriaThe following checklist was chosen for auditing antibiotic usage Table .The following steps were implied:a) Sensitised all the clinical practitioners prescribing antibiotics to patients as mandated by NABH. Sensitization programs on prescription audits using the hospital's WhatsApp group chats, weekly meetings for all doctors and nurses department-wise, and recommendations and amendments done as per the accreditation policy.b) Feedback forms collected from the treating doctors and the residents. Sixty-six doctors filled the forms as mandated by the Accreditation Committee.c) Awareness of the availability of generic drugs and Food and Drug Administration (FDA)-approved drugs in the store is emphasized.d) Hospital infection control bulletin released quarterly was always updated on recent updates on the drugs, banned drugs, and fixed doses released by the FDA and the Central Drugs Standard Control Organization.e) Collected data on antibiotic prescribing prior to the culture and after culture reports.An effective awareness program on antibiotics usage was conducted regularly for junior doctors and the nursing staff. Nurses maintained the checklist for medication errors, near misses, transcription errors, preparation or dispensing errors, administration errors ), and unauthorized dose given). Further monitoring and sensitization were done for the availability of medications in the hospital pharmacy. We, from the Hospital Infection Control Committee (HICC), were monitoring the availability of antibiotics, storing the drugs at appropriate temperatures according to manufacturer’s instructions. This was followed as per the hospital committee and pharmacotherapeutic committee recommendations. The checklist was prepared for near-expiry drugs in the next three months that were returned to the pharmacy, drugs at appropriate temperatures according to the manufacturer’s instructions, drugs reconstitution and administering, use of drugs left over in the syringes, and finally discarding the left-over drugs as per the biomedical waste rule.Clinical practitioners who give antibiotics to patients were asked to fill out a survey on how well they understood the accrediting board's antibiotic prescription audit Figure .Ninety-five point four-five percent (95.45%) of the doctors attended the sensitization program, and all accepted to follow the standard prescribing protocols. Sixty-nine point seven percent (69.7%) of the doctors were aware of the availability of drugs in the hospital pharmacy stores. Seventy-four point two-four percent (74.24%) of the doctors were aware of the ongoing prescription audits.The treating clinicians were asked to complete a questionnaire on their antibiotic prescribing practices Figure .One-hundred percent (100%) of the treating doctors have given their recommendations for a proper culture and sensitivity report, and treat accordingly. Seventy-two point two-seven percent (72.27%) of the treating doctors were of the opinion of selecting the appropriate antibiotics based on hospital antibiogram. The importance of antibiograms from cultures and environmental surveillance was followed well only after sensitizing all the treating doctors. Ninety-five point four-five percent (95.45%) of the doctors were of the opinion of taking the permission of a higher authority to start high-end antibiotics.Feedback was received on the significance of culture reports in antibiotic prescribing Figure .Seventy-seven point nine percent (77.9%) of the prescriptions followed therapy according to the hospital antibiotic policy. Seventy-seven point one-zero percent (77.10%) of doctors recommended sample collection prior to antibiotic administration. Sixty-three percent (63%) of the patient’s clinical conditions improved with the antibiotics prescribed prior to the culture report. Of the 22.1% of the doctors who didn’t follow the hospital policy, 9.2% were more of viral infections, and the rest were high-end antibiotics without the approval of a higher authority.A survey was done to find out which antibiotics were the most commonly utilized in the hospital Figure .Antibiotics prescribed in the hospital were analyzed from 3893 prescriptions. Cephalosporins were frequently prescribed, cefotaxime was the commonest followed by ceftriaxone, pip/tazo, and amox/clav. Among the aminoglycosides prescribed, Netilmicin was commonly used followed by amikacin and gentamycin. The commonest injectable used was piperacillin/tazobactam, amox/clav A, imipenem, and amikacin.A survey was conducted to determine the most prevalent clinical circumstances in which antibiotics were administered inappropriately Figure .A total of 63 cases were noted; 61.9% of cases presented with viral fevers, and for these cases, further observation was not done, instead, antibiotics were started immediately. Fourteen point two-nine percent (14.29%) of diarrheal cases, 11.1% of allergic rashes, 9.5% of rhinitis cases mostly consisted of the pediatric population and were initiated with first and second-generation cephalosporins; 3.17% of patients presented with pain abdomen. Sensitization on antibiotic usage by the hospital accreditation board mandated observing and starting an antibiotic only if there was no improvement.The most mismanaged drugs in hospitals were studied Figure . The mosA survey looked at antibiotics often used in hospitals for surgical prophylaxis Figure .Staphylococcus species, and hence the surgeon preferred to add teicoplanin as a prophylactic drug to prevent surgical site infections in all major orthopedic cases.The total number of surgeries in the last six months was 585 (major surgeries) and 379 (minor surgeries). The total number of antibiotics prescribed as antibiotic prophylaxis was 514 cases, which includes 499 major surgeries and 15 minor surgeries. Eighty-six major surgeries were lower segment Cesarian section (LSCS), and prophylaxis was given only after cord clamping. The most common antibiotic used as surgical prophylaxis were cephalosporins, with ceftriaxone - 242 (47.08%), followed by ciprofloxacin - 89 (17.30%), amox/clav- 48 (9.33%), gentamycin - 42 (8.17%), pip/tazobactam - 36 (7%), cefuroxime - 36 (7%), teicoplanin - 13 (2.52%), and clindamycin - 8 (1.55%). Amendments were done after surgical site infections in orthopedic surgeries, where two cases showed growth of methicillin-resistant A survey of doctors was undertaken to ascertain the amount of time surgical prophylaxis was given before surgery Figure . This waAll the cases were given a test dose 24 hours prior. Most of the surgical cases received prophylaxis within 25 to 30 mins prior to skin incision. The checklist did not include LSCS since the prophylaxis was given after cord clamping.The number of days an antibiotic is prescribed for a full course of treatment for patients was obtained Figure . Mostly,The most common clinical conditions seen while initiating empirical antibiotic therapy were evaluated Figure .The most common presentation was urinary tract infections followed by respiratory tract infections, bloodstream infections, and skin and soft tissue infections where antibiotics were used.A poll was performed to find out if doctors prefer to prescribe generic or branded antibiotics Figure . Brand nClinicians were mostly prescribing brand names, with very few prescriptions showing the generic name. The brands available in the pharmacy stores were those prescribed by the treating doctors after the approval of the hospital pharmacotherapeutic committee and infection control team (for antibiotics). This policy was also approved by the accreditation committee.Antibiotics prescribing by physicians has become increasingly important across the world, owing to a rise in antibiotic use, illness prevalence, and drug resistance. Antimicrobials have played a key role in decreasing morbidity associated with the infectious complications of surgical operations, organ transplants, and cancer treatment, in addition to treating isolated episodes of infection. The global growth in bacterial resistance that is threatening the efficacy of antibiotics and antimicrobial resistance (AMR) is increasingly recognized as a serious public health issue -7. Only In India, health expenditure accounts for around 1.4% of GDP. In India, there are public and private healthcare systems; private-sector treatment is significantly more expensive than public-sector treatment. The Pharmacy Act of 1948 governs the dispensing of pharmaceuticals in India. In India, only licensed pharmacists and physicians are permitted to distribute medicine to patients. In 2017, India released its National Action Plan to Combat AMR (NAPAMR), which was in accordance with the worldwide action plan to combat AMR [Antibiotic prescription variation within and between nations is a growing topic that needs to be carefully addressed. This variance may suggest poor clinical management, which raises the patient's risk of adverse outcomes, wastes healthcare resources, and contributes to the societal rise of resistant strains -11. AccoIndia is the country that consumes the most antimicrobials. Additionally, antibiotic usage is causally connected to the formation of antimicrobial resistance . A propeAntibiotic prescription recommendations are provided at the national and state levels as well as in many cases in particular hospital advice papers. Regional and global specialists form groups to develop regional standards. The corporate sector's faulty prescription of antibiotics has been repeatedly documented in the developing world . In our In our study, though all opined that antibiotics should be started after culture sensitivity, only 72.27% of doctors agreed to commence the antibiotic treatment based on the result of the hospital antibiogram. Ninety-five point four-five percent (95.45%) of the doctors were of the opinion of taking the permission of higher authority to start high-end antibiotics. Sixty-one point nine percent (61.9%) of the antibiotics were prescribed only on the basis of clinical diagnosis of viral fever, 14.29% were prescribed on the clinical diagnosis of diarrhea, 11.1% were prescribed on the clinical diagnosis of allergic rashes, 9.5% were prescribed on the clinical diagnosis of rhinitis cases, and only 37% of the patients showed improvement in clinical conditions when antibiotics were prescribed without culture sensitivity. Before administering an antibiotic, the worldwide recommendation is to collect microbiological samples from hospitalized patients with suspected illnesses. In fact, starting antimicrobial therapy too soon can inhibit bacterial growth and prevent the establishment of a microbiological diagnosis, which is necessary for setting a focused antibiotic therapy . In a stStreptococcus pyogenes, it was demonstrated clearly how reducing macrolide use might lead to a reduction in AMR. Antibiotic resistance has decreased from 9.2% in 1997 to 7.4% in 2000, with a statistically significant link between regional macrolide resistance and consumption rates [In our study, out of all the patients who were prescribed antibiotics, only 91.8% of them actually needed them. Nine point two percent (9.2%) were given antibiotics, which could have been avoided as these patients were ruled out to have viral fever, streptococcal pharyngitis, or runny nose. If unnecessary antibiotic usage is reduced, resistance is reduced as a result. In a study on macrolide-resistant on rates . Antibioon rates . In anoton rates .Several methods have been recommended to minimize the overuse of antibiotics in upper respiratory tract infections (URTI) patients. Educational materials for physicians, audits and feedback, educational meetings, changes in the financial and healthcare systems, reminders, technological support systems, patient-target interventions, and multidimensional physician-target interventions are the most researched approaches. Studies have shown that interactive educational teachings and physician targeted interventions could reduce inappropriate antibiotic prescription by 20% . In a stIn our audit, the most prescribed antibiotics are cephalosporins (56.48%) followed by a beta-lactam /lactamase inhibitor combination 19.08%). Quinolones and carbapenems were less frequently used. In a study done by Remesh et al. , beta-la.08%. QuiIn this audit, surgical prophylaxis was given for 87.86% of cases (499 major surgeries and 15 minor surgeries) posted for minor and major surgeries in the last six months. The commonly prescribed antibiotics for surgical prophylaxis were cephalosporins, with Cceftriaxone - 242 (47.08%), followed by ciprofloxacin - 89 (17.30%), followed by amox/clav - 48 (9.33%), gentamycin - 42 (8.17%), pip/tazobactam - 36 (7%), cefuroxime - 36 (7%), teicoplanin - 13 (2.52%), clindamycin - eight (1.55%). And the surgical prophylaxis of antibiotics was given to 90% of the patients 25-30 minutes prior to the procedure, and 10% received them 45 minutes to one hour prior to the procedure. Antibiotics used before surgery have been found to reduce the risk of surgical site infections (SSIs). Antibiotic prophylaxis is used to guarantee that the medication is present in effective serum and tissue levels throughout the length of the procedure. A study of 2,847 patients having clean or clean-contaminated surgical procedures found that those who received antibiotic prophylaxis within two hours of incision had a 0.6% surgical site infection incidence. Patients who received prophylactic antibiotics more than three hours after the surgical incision had a twofold increased risk of surgical site infection, whereas those who received antibiotics more than two hours before surgery had a six-fold increased risk . AnotherIn our study, the duration of the antibiotics prescribed to the patients was not uniform and not as per the standard guidelines. Sixty-three percent (63%) of patients received antibiotics only for a duration of three days; 17% for five days; 15% for seven days, and 5% for more than a week. Also, only 77.9% reported having an adequate dosage of antibiotics as per the hospital administration policy. The term "optimal duration" refers to administering medication for the lowest period necessary to achieve clinical and microbiologic effectiveness. There are a variety of reasons why antimicrobial therapy should be limited to the shortest time possible. They include the possibility for fewer side effects, greater patient adherence, less resistance promotion, and lower costs . The infIn this audit, 87.7% of antibiotics were prescribed with brand names and 12.35% with generic names. In a study done by Remesh A, 10.5% were prescribed with generic names . In a stAs antibiotic resistance spreads, hospitals are now implementing antibiotic stewardship programs, surveillance systems are being built up, access to over-the-counter antibiotics is being restricted, and consumer awareness is being raised.By providing academic information to clinicians and recommendations based on microbiological evidence, inappropriate antibiotic use has been reduced. The monitoring of resistant strains both in the community and in hospitals provides important information for improved patient care. These results can be used to improve physician education, antibiotic surveillance, and antibiotic prescription trends in our environment.By the judicious use of antibiotics, we can reduce the evolution of antibiotic resistance in bacteria and extend the useful life of antibiotics that are still effective. Antibiotic-use patterns must be studied to address complications resulting from many antibiotics. Antibiotics should be chosen depending on the antibiogram of the area. By providing academic information to clinicians and recommendations based on microbiological evidence, inappropriate antibiotic use can be reduced. The monitoring of resistant strains both in the community and in hospitals provides important information for improved patient care. These results can be used to improve physician education, antibiotic surveillance, and antibiotic prescription trends in our environment.Antibiotic prescribing in hospitals can be improved by optimizing antibiotic selection, re-evaluating antibiotic treatment when diagnostic testing findings are available, and employing the shortest effective period of medication. Prescription audits should be performed on a regular basis to help hospitals rationalize their medicine prescriptions and enhance their overall quality.


These photocured BDM inks can be used to produce complex structural components and models with excellent mechanical and thermal properties, such as car parts, building models, and pipes.Photosensitive resins used in three-dimensional (3D) printing are characterized by high forming precision and fast processing speed; however, they often possess poor mechanical properties and heat resistance. In this study, we report a photocurable bismaleimide ink with excellent comprehensive performance for stereolithography (SLA) 3D printing. First, the main chain of bismaleimide with an amino group (BDM) was synthesized, and then, the glycidyl methacrylate was grafted to the amino group to obtain the bismaleimide oligomer with an unsaturated double bond. The oligomers were combined with reaction diluents and photo-initiators to form photocurable inks that can be used for SLA 3D printing. The viscosity and curing behavior of the inks were studied, and the mechanical properties and heat resistance were tested. The tensile strength of 3D-printed samples based on BDM inks could reach 72.6 MPa , glass transition temperature could reach 155 °C , and energy storage modulus was 3625 MPa at 35 °C . The maximum values of T In three-dimensional 3D) printing, objects can be fabricated through computer-controlled layer-by-layer accumulation of materials without using molds . The advD printinWith the rapid development of 3D printing technology, higher requirements have been put forward for the quality of light-cured 3D printing products. As printing materials for SLA technology, photosensitive resins mainly include epoxy, acrylic resin, and polyester resin ,14,15. IBismaleimide (BMI) is a high-performance thermosetting resin with good dielectric properties, high glass transition temperature, and excellent thermal stability, and it is widely used in aerospace, transportation, and machinery electronics, among other fields ,26,27,28From this viewpoint, we developed a novel bismaleimide resin for SLA 3D printing. The resin based on N,N′- bismaleimide–4,4′-diaminodiphenyl methane–glycidyl methacrylate (BDM-DDM-GMA) was prepared via a grafting reaction between BDM and DDM by adding a drop of GMA containing a copolymer inhibitor. The BDM-DDM-GMA presented herein not only effectively solves the shortcomings of the poor moldability of bismaleimide resin but also significantly broadens the application range of light-curing 3D printing resins.BDM, DDM, acetate anhydrous, acetone, tetraethylammonium bromide (TEAB), GMA, hydroquinone, 2-hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), 2,4,6-trimethyl benzoyl diphenyl phosphine oxide (TPO), 1-benzoylcyclohexanol (Irgacure 184), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), cyclic trimethylopropane formal acrylate (CTFA), trimethylolpropane triacrylate (TMPTA), and isobornyl acrylate (IBOA) were purchased from Aladdin Industrial, Inc.  Urethane methacrylate (YYUV-1), polyethylene glycol (200) dimethacrylate (YYUV-2), ethoxylated pentaerythritol tetraacrylate (YYUV-3), polyurethane acrylate (YYUV-4), and aliphatic urethane acrylate (YYUV-5) were supplied by Yongyue Science & Technology Co., LTD .First, DDM  was gradually added to a stirred solution containing BDM  and 200 mL acetone under a nitrogen flow at 30 °C; then, 1 mL of anhydrous acetate was added to the solution. Then, the temperature was increased to 60 °C and maintained for 2 h. After vacuumizing the system for 30 min, GMA , TEAB , and hydroquinone  were added to the solution, which was then stirred at 60 °C for 8 h to complete the grafting reaction of methacrylate groups. The product was removed while it was hot, and a small amount of residual acetone was removed using a rotary evaporator. The resulting brownish-red viscous product was BDM-DDM-GMA, and the yield was 95%.Photocurable BDM resins were prepared by homogeneously mixing BDM-DDM-GMA with HEMA and HPMA as reactive diluents, YYUV1–5, and photo-initiators TPO and Irgacure 184. SLA printer  was employed to produce 3D architectures. The model was designed using the SolidWorks software and subsequently layered with the help of printing software to control the ultraviolet (UV) light curing of the liquid resin; in this way, the photosensitive inks can be layered and printed according to the pre-designed modeling structure. The resulting samples were washed with ethanol and dried under an air flow. Finally, the samples underwent UV light curing for 10 min and, subsequently, thermal curing via the following procedure: 160 °C/1 h + 180 °C/1 h + 200 °C/1 h + 220 °C/2 h.−1, with 16 scans per spectrum. 1H nuclear magnetic resonance (NMR) spectra were obtained on a Bruker (Germany) Avance-neo 400 MHz spectrometer using tetramethylsilane (TMS) as an internal standard and deuterochloroform (CDCl3) as the solvent. Rheological behaviors of the inks were investigated by a rheometer  at 25 °C with a parallel-plate configuration . The range of steady-state shear rate was set from 0.1 to 100 s−1. The kinetics of the photocuring process were also investigated with the rheometer equipped with an ultraviolet light emitting diode (UV LED) accessory that had an irradiation power of 80 mW/cm2. The gap between two geometries was 0.1 mm. The upper geometry was made of aluminum, and the lower geometry was made of transparent polymethylmethacrylate. The experiment lasted a total of 80 s, and the UV LED light was applied at 20 s. The mechanical properties were evaluated using a universal material testing machine . Specifically, the tensile and flexural behaviors were measured according to International Organization for Standardization (ISO) 527 and ISO 604 standards, respectively. Dynamic mechanical analysis (DMA) was performed using a TA Instruments (USA) DMA Q800 apparatus. DMA tests were carried out from 35 to 300 °C at a heating rate of 3 °C min−1 at 1 Hz, and the dimensions of each specimen were rectangular (35.0 mm × 10.0 mm × 3.0 mm). Thermogravimetric analysis (TGA) was performed on a TA Instruments (USA) STA449C machine in the range of 35–800 °C under a nitrogen atmosphere with a flow rate of 100 mL min−1 and at a heating rate of 10 °C min−1. The surface fracture morphology of the 3D-printed parts was observed by a scanning electron microscope  at 2.0 kV. Conductivity was improved by adding a thin layer of gold particles on the fracture surface.Fourier transform infrared (FT-IR) spectra were recorded with an attenuated total reflection (ATR) stage on a Thermo Fisher Scientific (USA) Nicolet iS10 spectrometer, at a resolution of 4 cmThe synthesis of the photosensitive BDM oligomer is illustrated in 2, can be observed in the BDM-DDM spectrum at 3450–3360 cm−1, the peak at 3000–2800 cm−1 corresponds to the –CH2– stretching vibration, appearing after the imide ring addition, and the peak at 1615 cm−1 results from the bending vibration of –NH–; moreover, the peak at 690 cm−1 observed in the BDM curve is no longer present in the BDM-DDM spectrum, confirming that the C=C double bond on the imide ring underwent Michael addition by the amino group. At the same time, the peak at approximately 1712 cm−1 did not disappear, indicating that the reaction had no effect on the imide group and that BDM-DDM reacted successfully. By comparing the IR spectra of BDM-DDM-GMA and BDM-DDM, a new peak can be observed in the former at 943 cm−1, which is due to the methylene group generated after the reaction of the amino group with the epoxy group in GMA. The appearance of this peak indicates the successful grafting of GMA. In addition, the symmetrical stretching vibration peaks of ester bonds at 1294 and 1169 cm−1 are strengthened, confirming the successful reaction between GMA and BDM-DDM.The chemical structures of the intermediate BDM-DDM and BDM oligomer were confirmed by FT-IR spectroscopy a. The ab1H NMR spectroscopy was employed to characterize the BDM oligomer. As shown in 2– and –CH– groups around the hydroxyl group, formed after the ring-opening reaction of the epoxy group. The chemical shifts at 3.95 and 3.71 ppm can be assigned to the protons in the –CH2– group between two benzene rings in BDM and DDM, respectively. The chemical shift at 2.91–3.15 ppm corresponds to the protons in the amino group. In summary, the results of FT-IR and 1H NMR spectroscopies prove that the BDM-DDM-GMA oligomer was successfully synthesized.Excellent solubility is essential for BDM-DDM-GMA to be a light-curing 3D printing material. The rheological properties and curing kinetics of ink are crucial for SLA 3D printing products, since they determine their printing ability, resolution, and appearance ,33. The The UV LED accessory of the rheometer was used to investigate the curing behavior of the inks. The curing process is characterized by free radical polymerization, accompanied by a minor contribution of cationic polymerization. The variations in storage moduli during the curing procedure are shown in The mechanical properties of the samples printed using commercial ink and BDM inks were tested to evaluate the effect of the introduction of BDM-DDM-GMA. In addition to the tensile strength, the flexural strength was obtained from flexural tests b. The fl−2. The figure shows that for BDM-DDM-GMA content from 0% to 25% w/w, the impact strength increased. As expected, by adding 25% w/w BDM-DDM-GMA, the impact strength reached the optimum value of 4.29 kJ m−2, to be compared to the value for the commercial ink, 2.77 kJ m−2. With a further increase in BDM-DDM-GMA beyond 25% w/w, the impact strength shifted downward to 3.73 kJ m−2. In In addition to the tensile and flexural properties, the impact strength and hardness of 3D-printed products were tested to further investigate the effect of BDM-DDM-GMA. As presented in To further study the effect of different mass ratios of BDM-DDM-GMA on the properties of samples 3D-printed using BDM inks, their tensile fracture surfaces were observed by SEM, and the results are shown in In addition to the mechanical properties, the viscoelastic properties of 3D-printed samples prepared with commercial and BDM inks were further studied using a DMA. The storage moduli and loss tangents (tan δ) of the samples as a function of temperature are illustrated in e) of the samples was estimated from DMA using the following equation [g + 50 °C, where Tg is the glass transition temperature), R is the gas constant (8.314 J mol−1 K−1), and T is the absolute temperature at Tg + 50 °C. As can be seen from the resulting values presented in 2 mol m−3), which is mutually supported by our previous analysis. For higher BDM-DDM-GMA content, the crosslinking density value then decreases (1.57 × 102 mol m−3 for BDM-6). One could hypothesize that in these conditions, the benzene ring could hinder the polymerization to some extent and thereby induce a decrease in crosslinking density.Furthermore, the crosslinking density νeg of the samples was also obtained from the tan δ results. For the samples printed using commercial ink, the value of Tg was 75 °C. After introducing BDM-DDM-GMA into BDM inks, the Tg exhibited significant improvement. With an increase in the BDM-DDM-GMA content, Tg first increased, reaching the highest value (155 °C) at the optimized loading of 25% w/w BDM-DDM-GMA ; then, it decreased , temperature at the maximum degradation (Tmax), and char residual (CR) yield. All samples presented only one stage of thermal degradation. For the samples printed using commercial ink, T-5%, T-50%, and Tmax were 287.5, 357.6, and 342.5 °C, respectively. When the BDM-DDM-GMA content increased in the BDM inks, the T-5%, T-50%, and Tmax were significantly enhanced. Such an effect became more pronounced at a relatively lower BDM-DDM-GMA content (≤25% w/w). The maximum values of T-5%, T-50%, and Tmax were attained by the samples based on the BDM-5 ink, reaching 351.5, 449.6, and 451.9, respectively. The improvement in the thermal properties can be rationalized by considering the motion, breakage, and thermal decomposition of the polymer chains. Because the macromolecular chain of BDM-DDM-GMA, which has a rigid benzene group, increases the rigidity at the molecular level, the macromolecular motion is limited during the process of thermal degradation. In addition, the CR at 800 °C increased from 7.3% to 14.0% with the change in BDM-DDM-GMA content, indicating an improvement in the thermal resistance capacity.To further assess the thermal properties of the samples printed using the BDM inks, TGA was carried out at a heating rate of 10 °C minFurthermore, the samples printed with BMD-5 ink and commercial ink were heated in a muffle furnace at different temperatures for 30 min. As shown in We collated some data on the mechanical and thermal properties of 3D-printed samples using different photosensitive inks, as shown in To further assess the properties of the BDM inks in practical applications, some mechanical elements and models including rockets, towers, and gears were fabricated by deposition of a 0.1 mm thick layer using a 3D printer, as shown in g of 155 °C , and energy storage modulus of 3625 MPa . The maximum values of T-5%, T-50%, and Tmax of the samples printed using BDM-5 reached 351.5, 449.6, and 451.9 °C, respectively. We believe that the SLA-based 3D printing capability will be enhanced significantly owing to these high-performance photocurable BDM inks. We foresee the application of these photocurable BDM inks to produce complex structural components and models with excellent mechanical and thermal properties, such as car parts, building models, and pipes.In this study, a novel photocurable BDM resin was synthesized from BDM, DDM, and GMA. Its excellent solubility, good fluidity, and UV-curing performance provide an excellent basis for its application in 3D printing. BDM-DDM-GMA can be prepared with other acrylic resins such as oligomers, HEMA and HPMA as reaction diluents, and TPO and Irgacure 184 as photo-initiators to produce BDM inks for SLA 3D printing. BDM inks can be employed to print parts and models with complex structures, and they exhibit excellent mechanical and thermal properties. In particular, 3D samples printed using the BDM-5 ink possessed a tensile strength of up to 72.6 MPa , T


In this study, experimental work was carried out on reinforced concrete (RC) beams strengthened with carbon fiber reinforced polymers (CFRP) plates. This study aims to examine the effect of the reinforcement ratio on the flexural behavior of these beams and propose a new model for predicting the debonding moment. Six RC beams consisting of three control beams and three beams strengthened with CFRP plates were tested. The beams were simply supported and loaded with four-point bending. The test variable was the tensile reinforcement ratio . Analytical prediction using the fiber element method was also carried out to obtain the complete theoretical response of the beam due to flexural loads. The test results show that the reinforcement ratio affected the bending performance of RC beams with CFRP plates. Following this, the experimental data from 60 beam test results from published literature and this study were analyzed. From these data, it was found that the ratio of tensile reinforcement, the ratio of modulus of elasticity of concrete, the modulus of elasticity of the plate, and plate thickness all affect the value of debonding moment. A parametric study using fiber elements and the two-dimensional finite element method was also carried out to confirm the effect of these variables on debonding failure. These variables were then used to develop an equation to predict the debonding moment of RC beams strengthened with CFRP plates, using simple statistical analysis. This analysis resulted in a simple model for predicting the debonding moment. Then the model is entered into a computer program, and the complete response of the cross-section due to debonding failure can be obtained. Buildings that experience deterioration in strength, damage, or changes in the design code during their service lifetime need to be strengthened or repaired to meet design code specifications. One way to do this is to use externally bonded Carbon Fiber Reinforced Polymer (CFRP) plates. These have been extensively researched and used to increase the bending capacity of reinforced concrete structures for more than three decades and are reported to have shown promising results ,18,19,20Experimental studies of externally strengthened RC beams with CFRP plates that several previous researchers have carried out showed premature failure indicated by the loss of the bond between the concrete and the CFRP plate ,15,16,17Previous research has shown that the capacity of a beam strengthened with CFRP plates is influenced by several variables, including the tensile reinforcement ratio , the thif0.41) when the attachment length of the plate was less than the effective attachment length, and tf to the power of 0.32 (tf0.32) when the attachment length was more significant than the effective attachment length.The effect of variations in the CFRP plate layer on reinforced concrete beams was demonstrated in the study by Ahmed et al. . Those sfc’ to the power of 0.34 due to the influence of the compressive strength of the concrete (fc’). In another study, Mansour [The effect of the modulus of elasticity of the FRP plate (Ef) on the ultimate bond strength was studied by Sayed . Sayed f Mansour  showed tIn previous studies, models for predicting flexural debonding moment in FRP-plated reinforced concrete beams were proposed by Oehlers  and TengThis present study examines the effect of the reinforcement ratio on the flexural behavior of RC beams with CFRP plates and proposes a model for calculating the debonding moment. In this work, data from previously published studies regarding the flexural strengthening of reinforced concrete beams by externally attaching CFRP plates to the tensile surface were collected, providing a database of 60 experimental beam test results from 17 studies. These were analyzed to achieve the objectives of this study. Cross-sectional analysis based on theoretical moment-curvature determination was also carried out to theoretically predict the flexural capacity of CFRP-plated RC beams. The calculation process was supported by a computer program called Reinforced Concrete Cross Section Analysis (RCCSA) ,24,25. TThe study by Thamrin et al.  consisteThe compressive and transverse reinforcement for all beams were 10 mm diameter bars with a yield strength of 355 MPa. The tensile reinforcement used in the test specimens had a 13 mm diameter and a yield strength of 448 MPa. Closed type transverse reinforcement with 100 mm spacing was used on all tested beams to avoid premature collapse due to shear forces. A ready-mix company supplied the fresh concrete, and the compressive strength of the concrete at the age of 28 days was 20 MPa.® UC Composite Laminate Strip laminated by FYFE Co. LLC, USA. The CFRP plates were 1.9 mm thick and 50 mm wide. CFRP plates were glued to the tension face of the strengthened beams with epoxy adhesive by FYFE Co. LLC, as shown in ® S Epoxy was applied as the main layer on the prepared concrete substrate and Tyfo® TC Epoxy was applied to a thickness of 2 mm on the substrate before applying the CFRP plate. Installation of CFRP plates on beams was carried out by certified applicators, as shown in The CFRP plates used were obtained from a roll of TyfoTesting of simply supported beams was carried out by applying two concentrated loads 400 mm apart. The load was applied by a 500 kN capacity of a hydraulic actuator. Load cell and linear variable displacement transducers (LVDTs) were used to measure the deflection of the beams. Load cell and LVDT’s were connected to a data acquisition system, and the data was collected on data media. The deflections of the beam located at three positions were recorded continuously. In each test, the load was gradually increased until collapse occurred. Test setup, the position of the load, and LVDT’s on the tested beam are shown in Flexural analysis of the reinforced concrete cross-section using the fiber element method was carried out to obtain the complete flexural response of the cross-section with CFRP plates due to the applied bending moment. εi, εsi, and εp) and stress level at each incremental curvature (φ) and the equilibrium of the plated cross-section was determined by an iterative process. Once the equilibrium conditions for the cross-section were fulfilled, the moment at the corresponding curvature was calculated by multiplying the internal forces with the corresponding moment arms (yi). Then the calculation process was repeated until the maximum compressive strain of εcm = 0.003 was reached.The magnitude of the internal forces was then obtained by using the corresponding strain M in a square cross-section of concrete, as shown in Equation (8), was used.tf is the tensile strength of concrete, I is the moment of inertia, and y is the distance from the centroidal axis of the beam cross-section.In this study, the author modeled the debonding moment using basic equations from bending theory. The equation for calculating the crack moment (y = h/2 and a moment of inertia I = (1/12) bh3, we modified Equation (9) as;Assuming cE) with that of the plate (pE) on the debonding load. Furthermore, cE/pE, and plate thickness ratio significantly affect the debonding load.The experimental test results of the study by Thamrin et al.  and RosscE/pE is expressed as β and (3) the effect of plate thickness as pt. The effect of these three variables is shown in Equation (10).Therefore, the three variables that affect the debonding moment applied in the model proposed in this study are: (1) the effect of the longitudinal tensile reinforcement ratio is expressed as tρ is the ratio of tensile reinforcement, cE/pE, cE is the modulus of elasticity of concrete, pE is the modulus of elasticity of the plate, pt is the plate thickness, wb is the width of the RC beam, h is the height of the rectangular concrete member, and tf is the splitting tensile strength; if the splitting tensile strength is not determined from tests, then the value of the concrete tensile strength can be calculated as tf = c’f/10.Simple statistical analysis was performed to determine the value of the constants To assess the accuracy of the proposed model, we used the test results from this study, selected additional data from the literature ,15,16,17Comparison of literature models of the debonding load  was implemented in the RCCSA software. The value of the debonding moment can be calculated after all of the variables in Equation (11) are entered into the data input block. For each step of incremental curvature, the obtained moment value is checked. The axial stiffness of the CFRP plate is removed when the moment value reaches the debonding moment value obtained from Equation (11).terature ,15,16,17The comparison between analytical prediction and experimental data show a considerable variation due to several factors, including the bond behavior between the FRP plates and concrete, which is not the same in every case reviewed in this study; this is not the scope included in this study. The constant Bending capacity and debonding load of six reinforced concrete beams with and without CFRP plates were measured and the results were combined with an extensive dataset drawn from the existing literature. These data were used to construct a predictive mathematical model for debonding moments. Results from this model were then compared with the bending capacity of the beam with the different tensile reinforcement ratios from the experimental test results and previously proposed models. The following conclusions are drawn.Reinforced concrete beams strengthened with CFRP plate have a 10% to 50% higher flexural capacity than unplated beams depending on the value of the tensile reinforcement ratio.Failures in reinforced concrete beams with small reinforcement ratios (1% and 1.5%) are debonding failures due to the delamination of CFRP plates. In reinforced concrete beams with a reinforcement ratio of 2.5%, flexural failure occurs without delamination on the CFRP plate. These results indicate that an increase in the tensile reinforcement ratio causes a reduction in the stress on the CFRP plate.The ratio of tensile reinforcement, plate thickness, the ratio of modulus of elasticity of concrete, and the modulus of elasticity of the plate all affect the debonding load of reinforced concrete beam strengthened with the CFRP plate at the bottom of the beam.The fiber element method predicts the response of reinforced concrete sections with CFRP plates with a high degree of accuracy. The debonding load calculated using the proposed model compares conservatively to the experimental value.Due to safety considerations and optimization of the capacity of the CFRP plate to carry the load, the value of


The increasing demand for reconstructions of concrete structures and the wide availability on the market of surface protective products and systems could lead to misunderstandings in the decision of the most effective solution. Surface protectors have become increasingly widespread in recent years in concrete restoration interventions thanks to their properties: they are able to protect the substrate from aggressive agents and consequently extend the useful life of the structures. The aim of this article is first of all to present the surface protective treatments available on the market, outlining their strengths and weaknesses. Subsequently, a characterization of seven different commercial coatings for reinforced-concrete structures is provided, taking into account chemical nature, fields of use and effectiveness, both in terms of physic and elastic performance and resistance to aggressive agents that undermine the durability of the treated concrete elements. In recent years, the concept of sustainability has gained ground in the construction sector, and a particular attention has been paid to the durability of the structures ,2. In faThe penetration of aggressive external agents such as carbon dioxide or chlorides is what is mainly responsible for the deterioration of reinforced-concrete structures ,6,7. ForThe aim of this paper is to outline the main protective surface treatments by analyzing their characteristics and to define, through a careful analysis of the properties, the selection criteria for each protective product or system in relation to the field of use and the expected performance. (a)Polymeric and cementitious coatings(b)Hydrophobic impregnations(c)Pore-blocking treatmentsTo date, the surface treatments can be divided in three different macrocategories, in accordance with European Standard EN 1504-2 :(a)PolymThe surface coatings are defined as continuous films able to act as a physical obstacle to limit the penetration of aggressive substances into concrete elements. There are basically two different types of surface coatings: the polymer-based and cementitious protective coatings. The first ones promote the formation of a dense polymeric film with a thickness of about 0.1–1 mm on the concrete surface while the second ones realize a low-permeability cement-based layer with a thickness of about 2–10 mm. Traditional polymeric coatings have always been widely used in the construction sector. The main categories of polymeric coatings are epoxy resins ,19,20, a(a)The use of polymers strongly reduces the microcracks formation in the coatings, reducing the penetration of aggressive substances;(b)The pore structure of polymer-containing cementitious mortars is finer than that of traditional cement-based composites, further improving the impermeability of coatings;(c)The low-elastic modulus of the cementitious coatings enhances their crack-bridging capability, ensuring high performances even in the presence of cracked concrete.Cementitious coatings are cement-based mortars manufactured with a huge number of polymers  able to improve the mechanical properties , the chemical resistance and the impermeability of cement mortars. The protective effects of cementitious coatings on concrete structures can be summarized as follow:Emerging solutions for concrete protection based on alkali-activated materials and geopolymers show rapid setting times, excellent bond strength and durability, low water and chloride permeability and high freeze-thaw resistances. Moreover, these new coatings also possess an electrolytic conductivity, which can allow them to act as a protective layer for concrete and skin sensor for structural health monitoring. To date, this kind of coating is still in the experimental phase , but it is extremely promising and close to being widely used on real reinforced-concrete structures. Hydrophobic impregnations perform their task of avoiding the penetration of aggressive substances in liquid phase into the concrete by increasing the contact angle (the surface is considered hydrophobic when the contact angle is greater than 90° ) withoutImpregnating coatings  are able to block the capillary pores of the concrete and consequently improve the impermeability of buildings ,29. GeneThe choice of the ideal surface treatment strongly depends on the purpose of the work: protection against the ingress of aggressive substances into concrete and protection against the physicomechanical actions that occur during the service life of a structure or both. The following are the main properties of the surface treatments commercially available for concrete protection.First of all, it must be stated that the mechanical performance of the substrate cannot be improved in relation to the performance of the treatment, since the latter is not able to modify the porosity of the concrete; however, it is able to prevent the deterioration of concrete performance. In this regard, the compressive strength is not a noteworthy parameter in the examination of the treatments. A more important parameter for the surface treatments is the bonding strength; good adhesion to the substrate ensures its long-term performance and protection of concrete . ExperimAnother important indicator of the effectiveness of a treatment is the abrasion resistance, since it is able to evaluate of the service life of surface-treated concrete under repetitive traffic loadings ,39. ManyThe crack-bridging ability is the property of the coatings to cover cracks formed in the concrete substrate , keepingThe resistance of the treatment against possible alterations promoted by the environment in which they are located or by the tasks they must perform is very important for the success of a protection intervention. Research showed that temperature and ultraviolet radiation highly affected the efficiency of surface treatments. Vries  studied In most cases, the success of the protection is related to the durability of the concrete-surface treatment systems ,49. SincIn a concrete structure, chlorides can penetrate into the cement matrix and initiate degradation phenomena due to diffusion under the influence of a concentration gradient, migration in an electrical field or absorption due to a capillary action . In most2, calcium-silicate-hydrate (C-S-H) and CO2 to form CaCO3, silica-rich C-S-H and amorphous silica gel [2 and the reactivity of CO2 with the concrete. They depend on the pore system of hardened concrete and the exposure condition [Especially in urban or industrialized areas, the problem of carbon dioxide penetration is relevant. Carbonation is a chemical reaction between Ca(OH)lica gel ; it is alica gel ,61. The ondition . Many stondition ,64,65.Although the treatments cannot fulfil the functions performed by the air-entraining additives against the phenomena related to freezing and thawing cycles, they can contribute to making the concrete substrate more resistant to cold climate by preventing the critical moisture content from being reached. Both the acrylic treatments and the polymer-modified cementitious coatings have a good behavior against the destructive phenomena induced by the freezing and thawing cycles; by contrast, the behavior of silane-based coatings has not yet been well defined and is debated by the scientific community: Basheer et al.  stated tIn order to provide a complete analysis able of evaluating some of the aspects previously described, 7 different commercial treatments  have beeThe pot life is defined as the maximum time during which a coating material supplied as separate components (product A and product B or powder and water) should be used after the components have been mixed together. This parameter was evaluated at room temperature by taking into account the longest period of time which the consistency met the requirements related to the laying of the coating. Results reported in The adhesion tests were carried out on samples before and after thermal cycles in presence of deicing salts. In particular, after the curing of concrete and the application of the protective coating, a core drilling is carried out that affects both the substrate and the protective one. Then, a plug is applied, and finally, at a speed of 0.05 MPa/s, the tear test is performed on one half of samples to evaluate the adhesion and the failure type. On the other hand, the other specimens were subjected to 50 thermal cycles  before the adhesion test. The resistance to carbon dioxide diffusion is an important parameter in the choice of a coating. To avoid any design errors or the impossibility of carrying out the restoration work in a workman-like manner, it is possible to integrate the missing concrete cover thickness by choosing a suitable protective. In light of this, EN 1504-2  sets a m2 greater than 300 m), epoxy-bitumen and acrylic elastomeric-based treatments have a resistance to CO2 penetration of just over 50 m. At the same time, in this study, the E and PMC are characterized by an Sd CO2 close to 100 m of equivalent air thickness. On the other hand, authors want to highlight that unpublished experimental results on polymer-modified cementitious coatings demonstrated that the Sd CO2 is strongly influenced by the type and dosage of polymer used in manufacturing the coating. In particular, it is possible to obtain carbon dioxide resistances up to those of polyurethane-based coatings. The results, first of all, highlight that all the protectives tested comply with the limits prescribed by EN 1504-2  for the In terms of water vapor permeability , the bes2h0.5. Results reported in 2h0.5), while A and AE treatments evidence a capillary absorption coefficient close to the standard limits of 0.1 kg/m2h0.5. By contrast, the waterproofing ability of polymer-modified cementitious coatings are lower with respect to the epoxy-based treatments, even if it is necessary to demonstrate that this property is also strongly affected by the type and dosage of polymer used in manufacturing the coating. In particular, a proper composition allows one to reach extremely low capillary absorption coefficients.Aggressive substances for the cement matrix are often transported by water by capillary absorption. For this reason, the EN 1504-2  standardThe ability to cover the cracks that occur in the substrate to avoid the penetration of aggressive agents turns out to be a fundamental parameter in the choice of a protective. The graph reported in In addition to the static crack-bridging ability, the capability of the coatings to take up the elongation resulting from the periodic movement of the crack sides was evaluated for different crack widths. After 1000 cycles with a maximum crack width of 500 μm, AE and P appear to be sound, while the A and PMC systems limit their dynamic ability to cover cracks of about 150 μm . On the In relation to the weight loss connected to a forced abrasion (EN 5470-1 ) listed The evaluation of the resistance to make contact with chemical agents is an important parameter closely related to the intended applications of the coating; due to these peculiarities, some protective products have not been tested because their low resistance against chemicals is commonly known . Table 6The analysis of the parameter of resistance to negative hydrostatic pressure becomes of primary importance for waterproofing underground structures such as retaining walls. For this purpose, not all the tested coatings are suitable; therefore, the test in compliance with EN 8298-8  was condThe fire resistance is a fundamental properties of building materials, and it was evaluated by determining the ignitability of products by direct flame impingement and the production of smoke and flaming droplets. Experimental results reported in All the samples were exposed to wetting and drying cycles and UV radiation in accordance with EN 1062-11  to deter(a)2 penetration and a proper water absorption; they usually do not have excellent crack-bridging capabilities and, due to their conformation, are not suitable for withstanding mechanical stress or contact with aggressive chemical agents. They can be used to protect concrete in structures not fully immersed in water or in contact with aggressive chemicals; finally, elastomeric acrylic coatings embrace a slightly wider market share given the crack-bridging properties that make them suitable for applications where an elasticity of the coating is required, such as the protection of residential buildings.Water-based acrylic and water-based acrylic elastomeric coatings are the best systems when it is necessary to maintain the original texture and/or a specific aesthetic finish is desired. Acrylics have an excellent resistance to CO(b)Polyurethane and epoxy resin-based coatings, whether they are epoxy, epoxy-polyurethane or epoxy-bituminous can be used to protect concrete structures subject to continuous contact with water and aggressive chemicals. The main applications of this family of coatings are the protection a of reinforced-concrete structures subjected to severe environmental aggressions such as sewage collectors, purification plants (settling and aeration tanks), and bridge decks. The limits of epoxy protectives are the high resistance to vapor diffusion which could compromise the durability of coatings applied on wet substrates and the reduced crack-bridging capability that preclude their use on cracked concretes. The EB, EP and P, on the contrary, shows good crack-bridging ability, which makes them suitable for applications where a good ability to cover cracks is required, such as waterproofing of canals or containment tanks.(c)Polymer-modified cementitious coatings have excellent resistance to steam penetration and crack-bridging ability, as well as a high resistance to hydraulic pressure. They can be applied in the protection of both new concrete structures or during restoration works. The high waterproofing properties make these products suitable for the protection of reinforced-concrete structures such as tanks, fountains, wells, flower boxes or in any case of structures in continuous contact with water without extremely aggressive chemical agents. Their elasticity makes these protective products suitable for under-tile applications typical of the restoration works of projecting structures such as terraces and balconies. Therefore, it is necessary to highlight that the main properties of these coatings are strongly related to the type and dosage of polymer used during their manufacturing.In light of the scientific literature review and tests performed on protective products, the following conclusions can be drawn: