A novelty in the presented research is the evaluation of the fracture toughness of concretes with two mineral additives, assessed at an early age. During the tests, the structures of all composites and the nature of macroscopic crack propagation were also assessed. A modern and useful digital image correlation (DIC) technique was used to assess macroscopic cracks. Based on the conducted research, it was found the application of SF to FA concretes contributes to a significant increase in the fracture toughness of these materials at an early age. Moreover, on the basis of the obtained test results, it was found that the values of the critical stress intensity factor of analyzed concretes were convergent qualitatively with their strength parameters. It also has been demonstrated that in the first 28 days of concrete curing, the preferred solution is to replace cement with SF in the amount of 10% or to use a cement binder substitution with a combination of additives in proportions 10% SF + 10% FA. On the other hand, the composition of mineral additives in proportions 10% SF + 20% FA has a negative effect on the fracture mechanics parameters of concretes at an early age. Based on the analysis of the results of microstructural tests and the evaluation of the propagation of macroscopic cracks, it was established that along with the substitution of the cement binder with the combination of mineral additives, the composition of the cement matrix in these composites changes, which implies a different, i.e., quasi-plastic, behavior in the process of damage and destruction of the material.This paper presents the results of the fracture toughness of concretes containing two mineral additives. During the tests, the method of loading the specimens according to Mode I fracture was used. The research included an evaluation of mechanical parameters of concrete containing noncondensed silica fume (SF) in an amount of 10% and siliceous fly ash (FA) in the following amounts: 0%, 10% and 20%. The experiments were carried out on mature specimens, i.e., after 28 days of curing and specimens at an early age, i.e., after 3 and 7 days of curing. In the course of experiments, the effect of adding SF to the value of the critical stress intensity factor— Such actions, which are undoubtedly pro-ecological, directly affect:Currently, many research centers conduct tests on the separate use of SF ,14,15,16It should be noted that several basic properties of OPC–FA–SF concrete, such as consistency, setting time, workability, sorptivity, compressive strength, durability and resistance to migration corrosive substances, were provided so far in papers ,46,47,48VP-δ), crack mouth opening displacement (VP-CMOD) and crack tip opening displacement (VP-CTOD) were also analyzed in papers [Furthermore, in papers ,48,49, tn papers ,49. BaseHowever, from previous reports, it is known that the addition of FA to concrete has a positive effect on the parameters of fracture mechanics of 28-day and older concretes and a negative effect on the properties of composites at a young age ,60,61,62Therefore, in order to supplement the previous information included in papers ,49,50,51Microcracks that may appear in the structure of concrete at an early age negatively affect the progress of the final strength of the composite and reduce its fracture toughness. Therefore, it is important to track how this important property of the material changes, i.e., fracture toughness from the beginning of the formation of the composite structure until it is cured.Moreover, they are also very important from a technical point of view. The early strength of concrete is extremely important in today’s construction industry. Due to the pace of construction and the number of investments in the area of road, service, residential and industrial infrastructure, time plays an extremely important role.Monolithic massive constructions, where the young concrete is subjected to load increases during the subsequent stages of construction of the structure as a result of which numerous technical decisions must be made depending on the instantaneous strength of the concrete or its other properties, such as time of stripping the formwork, moving the sliding formwork, allowing young concrete to be subjected to technological and assembly loads, etc.;Prefabricated reinforced concrete constructions, where it is important to know the interoperational strength, e.g., formwork stripping, transport, storage, shipping, assembly;Prestressed reinforced concrete constructions, in which it is important to know the possible short-term losses of prestressing forces or not fully cured concrete.It should be noted that the knowledge of parameters of fracture mechanics for young concrete is particularly important in the following concrete construction areas:Siliceous FA used in the amount of approx. 20% of the cement mass significantly improves the mechanical parameters of concrete, e.g., their fracture toughness after 28 days of curing. However, the disadvantage of this solution is the reduction of the early strength of concrete. The article attempts to increase the early strength of FA concretes using a second pozzolanic additive. The experimental tests were carried out in order to confirm the positive effect of the applied modifications on the early parameters of compressive and tensile strength as well as fracture toughness of concrete. The presented research results can be practically used in many areas of construction, where the pace of construction works plays a decisive role. Moreover, the obtained test results may be helpful in selecting the composition of concrete mixtures containing FA and SF to be used in concrete and reinforced concrete structures subjected to loads at an early age.Therefore, in order to assess strength parameters and parameters of fracture mechanics of young concrete, the tests were conducted after 3, 7 and 28 days following the preparation of batches of concrete.The parameters of concretes modified with FA in the amount of up to 30% have already been fully tested, e.g., ,55,56. Tfcm), splitting tensile strength (fctm) and fracture toughness of young and mature concretes containing two pozzolanic additives, i.e., FA and SF. The analyses took into account the basic parameter of concrete fracture toughness determined under Mode I fracture. The parameter of fracture toughness assessed in the tests was a critical stress intensity factor ;Loss of ignition by burning the individual materials for one hour at 1000 °C;Color—visually.The chemical composition of both additives was determined by the XRF method. A Epsilon 3X spectrometer was applied . On the other hand, analyzed physical parameters were assessed as follows:In addition, Based on the pictures shown in On the basis of the observations of SEM FA pictures shown in The observation of SF grains, shown at 3 different magnifications in Moreover, 0–2 mm pit sand as fine aggregate, 2–8 mm gravel as coarse aggregate, pipeline water and plasticizer were used to prepare concrete mixtures. The tests assessed the combined effect of the addition of both wastes, i.e., FA and SF. SF had a constant amount of the additive, i.e., 10%, the amount of FA was varying. In each series of concrete, OPC was substituted with additives by weight.Mixture without additives (FA00+SF00);Mixture without FA additive and with a 10% SF additive (FA00+SF10);Mixture with a 10% FA additive and with a 10% SF additive (FA10+SF10);Mixture with a 20% FA additive and with a 10% SF additive (FA20+SF10).Four concrete mixtures were used for testing the basic strength of materials characteristics and the fracture toughness, which are as follows:The detailed composition of the above concrete mixtures was given in .fcm, according to PN-EN12390-3 [6 cube specimens (150 mm) for compressive strength tests—N12390-3 ;fctm, according to PN-EN12390-6 [6 cube specimens (150 mm) for splitting tensile strength tests—N12390-6 ;6 beams  for fracture toughness tests at Mode I fracture—endation .For each type of concrete mixture and for each curing time, the following were made:All tests were carried out after 3, 7, and 28 days of curing.Both compression and tensile strength were tested using a compression machine  with a maximum load of 3000 kN. The specimens were loaded statically.Fracture toughness tests, under Mode I fracture, were conducted in accordance with the draft guidelines of RILEM recommendations . The resThe research results were collected thanks to the recording of the results from the press  and clip gauge axial extensometer, which was placed on the clamping test grips. The test setup apparatus with all details is presented in F)–crack mouth opening displacement (CMOD) curve was recorded. The exemplary curve of F–CMOD is shown in For each of the tested cuboidal specimens , the loaMaximum load obtained in the tests;F–CMOD relationship, highlighted in blue (Ci) in Tangent in the first phase on the F–CMOD relationship, highlighted in purple (Cu) in Tangent in the second phase on the It should be noted that the most important data obtained for each of the graphs were :Maximum Additionally, the digital image correlation (DIC) technique was used to assess the shape and trajectory of the crack paths in particular concretes. This modern and increasingly often used measurement method allows for accurate and precise tracking of the cracking processes on the surface of concrete elements during the progressive crack propagation process. Thanks to it, it is possible to distinguish subtle differences in the shape of macrocracks depending on changes in the composition of the tested concretes. Such experiments provide valuable information and are a valuable supplement to the test results of concrete mechanical parameters.The average values of the analyzed mechanical parameters for particular periods of curing (with error bars) are given in From 48% to 81% (after 3 days);From 54% to 65% (after 7 days);From 26% to 34% (after 28 days).Based on the results presented in The positive changes in the mechanical properties of concretes containing fine and chemically active mineral additives  are directly related to the structural changes occurring in the composites. It has been proven in numerous papers to date that these materials significantly modify the microstructure of concrete with a changed cement binder composition, which translates into an improvement in their mechanical parameters. This phenomenon applies to ordinary concretes, e.g., ,92,93,94Due to the chemical composition , physicaDue to the undeniable relationship between the microstructure of concrete composites modified with mineral additives and the mechanical parameters of these materials, i.e., the processes of formation and propagation of microcracks, e.g., ,98, an aA high quantity of the hydration products in the form of ettringite (E) and calcium silicate hydrate of form I (C–S–H (I)) in FA-00+SF-10 and FA-10+SF-10 concretes can be seen in After four weeks, the FA-00+SF-10 and FA-10+SF-10 concretes already had a compact structure with barely visible CH crystals. This is due to the pozzolanic reaction that occurred between SF and CH, which led to a reduction in CH. Furthermore, in concretes containing FA—after 28 days of curing—the FA particle of approximately 8 μm and 2 μm were observed (circled with green dashed lines) c,d. MoreThe rapid development of the C-S-H phase after only 3 days of curing in FA-00+SF-10 concrete b and FA-The above assessment of the microstructure of concretes with a modified composition leads to the conclusion that the combination of chemically active and very fine-grained pozzolanic additives in the form of FA and SF clearly affects changes in the structure of composites at a young age and in the mature period. This is mainly reflected in the nucleation of additional regions of the C-S-H phase, which changes its structure from disordered to compact as the maturation process progresses . It is pIn addition to the microstructural analysis, an in-depth evaluation of the macroscopic cracks formed in the specimens after the tests were conducted. For this purpose, diagnostics with the naked eye and with the use of up-to-date and precise digital image correlation (DIC) technique were used.The beams were usually damaged as a result of a single large crack a, similaThis type of crack development is also confirmed by the results of experiments carried out with the use of the DIC technique ,106,107.The observed increase in the plasticity of concretes containing the combination of the mineral additives could probably be influenced by changes in their structure related to the slow development of additional phases in the cement matrix. The plasticity phenomenon was the most noticeable in FA-20+SF-10 concrete b. This cAdditionally, more brittle forms of failure were observed in concretes with the shortest curing time, i.e., those tested three days after the specimens were formed. This is also confirmed by the results presented by other authors, e.g., ,109,110.This paper investigates the behavior of ternary concretes after incorporating FA and SF. The main purpose of the new tests was to determine the effect of curing time of concretes modified with two additives on their fracture toughness assessed in accordance with Mode I fracture. During the experiments, the fracture toughness of young concretes (3 and 7 days old), and mature concretes (28 days old) were assessed.The experimental results revealed that the addition of wastes, such as FA and SF in OPC, very positively affects the mechanical properties of concrete. Therefore, it is planned to continue the topic discussed in the article and to extend the tests on fracture toughness of concretes containing siliceous fly ash and noncondensed silica fume in terms of the analysis of fracture processes in these materials in complex stress states and the assessment of the microstructure of composites, after the process of their destruction.Nonetheless, based on the obtained test results, the following conclusions can be drawn:Both FA and SF grains are characterized by a homogeneous structure and a similar particle morphology. In the case of FA, the grains have regular and spherical shapes with glazed surfaces  with a uConcrete composites at an early age with siliceous fly ash and noncondensed silica fume in the cement composition obtain higher values of strength parameters (30% to over 60%) as well as fracture mechanics parameters (40% to over 80%) in comparison to the values obtained for plain concrete.3/2 after 3 days, 1.30 MN/m3/2 after 7 days and 1.42 MN/m3/2 after 28 days.In all periods of curing, the maximum fracture toughness occurs in concrete containing only noncondensed silica fume. It is 1.05 MN/mSubstitution of the cement matrix with siliceous fly ash reduces the fracture toughness of concrete, mainly at an early age. This trend is more clearly noticeable in FA20+SF10 concrete.All series of modified concretes have higher values of fracture toughness in all periods of curing compared to FA00+SF00 concrete.A clear increase in values of the critical stress intensity factor is noticeable between the 3rd and 28th day of curing, particularly in the concrete from batches FA10+SF10 and FA20+SF10 . It meanFA00+SF-10 and FA-10+SF-10 concretes had the most developed phases in the structure of the cement matrix, in which C-S-H (I) and (E) dominated at a young age, while after 28 days, mainly the compact C-S-H phase dominated. Moreover, the structure of these concretes was more compact. In contrast, the reference concrete had less developed phases, while the composite with a greater amount of FA showed a distinct delay in growth and the transformation of the C-S-H (I) phase from a fibrous to a rigid form. It was also observed that the structures of these two materials were not fully ordered.The process of crack development in the reference concrete was brittle while in modified concretes—quasi-plastic.In the first 28 days of concrete curing, the preferred solution is to replace cement with SF in the amount of 10% or to use a cement binder substitution with a combination of additives in proportions 10% SF+10% FA.The composition of mineral additives in proportions 10% SF + 20% FA has a negative effect on the fracture mechanics parameters of concretes at an early age.


This Retraction follows an Expression of Concern relating to this article previously published by Portland Press.This article is being retracted from Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the Journal to multiple duplicated images in Figure 2, 3C, 3D, 3E and 4B. The Editorial Office has also been made aware that these images have been reused in multiple publications, which brings into question the validity of the data presented in this paper.The authors wish to retract the article. The Editor-in-Chief and Editorial Board agree with the retraction.


The complement system is a powerful mechanism of innate immunity poised to eliminate foreign cells and pathogens. It is an intricate network of >35 proteins, which, once activated, leads to the tagging of the surface to be eliminated, produces potent chemoattractants to recruit immune cells, and inserts cytotoxic pores into nearby lipid surfaces. Although it can be triggered via different pathways, its net output is largely based on the direct or indirect activation of the alternative pathway. Complement dysregulation or deficiencies may cause severe pathologies, such as paroxysmal nocturnal hemoglobinuria (PNH), where a lack of complement control proteins leads to hemolysis and life-threatening anemia. The complexity of the system poses a challenge for the interpretation of experimental data and the design of effective pharmacological therapies. To address this issue, we developed a mathematical model of the alternative complement pathway building on previous modelling efforts. The model links complement activation to the hemolytic activity of the terminal alternative pathway, providing an accurate description of pathway activity as observed in vitro and in vivo, in health and disease. Through adjustment of the parameters describing experimental conditions, the model was capable of reproducing the results of an array of standard assays used in complement research. To demonstrate its clinical applicability, we compared model predictions with clinical observations of the recovery of hematological biomarkers in PNH patients treated with the complement inhibiting anti-C5 antibody eculizumab. In conclusion, the model can enhance the understanding of complement biology and its role in disease pathogenesis, help identifying promising targets for pharmacological intervention, and predict the outcome of complement-targeting pharmacological interventions. The complement system as a part of the innate immunity builds a first line of defense of the body against foreign and altered host structures, such as pathogens and damaged cells. In contrast to the adaptive immune system, which takes days to weeks to mount a response, the complement system can react within seconds to minutes and therefore enables the body to quickly react to infections. Dysregulation of the system, however, has been identified as a major driver or significant contributor to several pathologies, ranging from the pathologic lysis of body’s own erythrocytes to the progressive loss of eyesight. The pathway’s highly diverse and interconnected architecture makes it difficult to identify promising points of therapeutic intervention and to predict clinical study outcomes. Building on previous modelling efforts, in this work we developed a mathematical model of the alternative pathway of the complement system that can explain experimental observations acquired over more than 50 years of complement research. These include results acquired in the laboratory as well as in patients. We envision that this work can be used to support the development of novel treatments for complement-mediated diseases at several key points such as target selection or design of clinical studies. As a first responder of innate immunity, the complement system, a network of more than 35 proteins, provides a powerful mechanism to mark and eliminate unwanted foreign and self-structures . ComplemThree pathways may activate the complement system, depending on the mechanism triggering response. Antigen-bound antibodies and sugar moieties initiate the classical (CP) and lectin pathway (LP), respectively . The thiThe complement system can eliminate cells within minutes, while the adaptive immune system requires weeks to mount an immune response. Complement can however harm self-structures when its regulation is out of balance, making it a major driver in several pathologies . The rarNevertheless, due to the cascade nature of the complement system and the numerous proteins, activation products, positive and negative regulators, as well as transient protein complexes involved, finding promising points of intervention and predicting the outcome of clinical trials remains a challenging task . A drug Mathematical models are often employed to facilitate the study of complex systems. Modeling techniques offer a means to formalize the available biological knowledge into a quantitative description of the system dynamics and obtain a reproducible testbed. A few models of the complement system have been developed, aiming to enhance our understanding of homeostasis and regulation –41. HiraThe aim of this work was to develop a mathematical model of the AP that allows to investigate complement activation as measured in vitro in laboratory assays and in vivo via clinical markers of disease. The goal was to develop a model that contains all relevant molecules and reactions as opposed to a reductionist approach. Such a model would allow probing the pathway at different nodes and facilitate the comparison to current and emerging experimental data. Being the most comprehensive model of the AP to date, the work by Zewde and colleagues  was usedHemolytic assays quantify the functional activity of the complement system by measuring the degree of erythrocyte lysis upon incubation in serum. They have been the cornerstone of complement research for over 50 years . TherefoIn summary, the AP model provides a platform to investigate pathway activity in vitro and in vivo and predict the outcomes of pathway modulation by disease and pharmacological intervention. The model may be useful to identify promising targets for drug development and assist the selection of biomarkers of clinical efficacy. It may also guide the definition of personalized treatments in the future, assuming the model can be adapted to match data from individual patients, and be used to study the optimal administration of drugs.We aimed at building a single model of the AP closely representing the biochemical pathway capable of reproducing in vitro and in vivo experimental observations. The structure of the proposed model is depicted in the known complement protein interactions in the fluid phase and their negative regulators the hemolysis of erythrocytes as a function of AP activation the synthesis (reaction 114–129) and degradation  was used. To simulate in vitro experiments involving rabbit or human erythrocytes, modules 1) to 3) were used. Details on each of the experimental setups and the respective implementation are provided below. All model equations and parameters are summarized in cat and a Michaelis-Menten constant Km , dissociation of DAF from C3bBbDAFhost and C3bBbC3bDAFhost (reactions 108 and 109), and dissociation of properdin from C3bBbPhost and C3bBbC3bPhost (reactions 110 and 111). Additionally, conversion of C5 by the convertase was modelled as an enzymatic reaction (reactions 55 and 82), with the associated kinetic rate constants  and KC5,m,C3bBbC3b(P)) obtained from the literature [kp,C3bH and km,C3bH) and CR1  were obtained from [20 and nascent C3b. Further steps of model development are described in the following sections.The model by Zewde and coworkers  was usedterature –45. Bindned from ,46. Finaned from  wIn order to reproduce pathway homeostasis in the in vivo setting, the non-AP specific production and elimination of complement proteins was incorporated in the model such that the reported in vivo steady state concentrations of all AP molecules would be obtained at homeostasis. This included the synthesis of all components that are not a result of the AP reactions such as C3, FH, FB, FD, as well as the elimination through processes such as renal filtration, receptor mediated uptake or metabolism that are not part of the AP. These processes were not mechanistically modelled, instead production rates and first order elimination rates were used. The elimination rate constants of C3a, C5a, and C3dg were obtained from literature reports . Due to 2O) hydrolysis  were decreased 102- and 105-fold relative to the in vitro parameterization, respectively, to compensate the increased pathway reactivity in vitro [Rates of protein synthesis were estimated under the assumption that the AP of healthy individuals produces negligible complement-mediated hemolysis. The rate constants were calculated in order to match protein steady state levels  and elimin vitro  and attakel,S, was calculated according to The elimination rate constant of cells and surface proteins, ks describes the physiological turnover of erythrocytes and kH the degradation due to hemolysis, as per Here H being the percent hemolysis  was calculated according to Ce is the concentration of erythrocytes (5*106 cells μL-1) and Ve the mean corpuscular volume (90 fL). Hemoglobin levels  were calculated using NA the Avogadro constant, Nh,e the number of hemoglobin molecules per erythrocyte  were assumed to be a function of hemoglobin concentration according to LDHmax, HLDH50, and LDH0 are parameters fitted to experimental data in PNH patients. While Several hematological markers are used clinically in the diagnosis and management of PNH disease. Hematocrit, hemoglobin and LDH levels provide relevant information for the monitoring of complement-mediated hemolysis and response to treatment. These markers were therefore included as part of the AP model. Hematocrit (6 cell-1 ) and MWh64.5 kDa ). FinallSSR) between simulated and experimental results of rabbit and human hemolytic assays [j, the SSR was calculated according to yi is the ith observation, mi(x) the model-predicted value with parameter value x, and n the number of data points. Normalization by the number of observations achieved equal weighing among studies. The objective function was defined as the sum of SSR for the five data sets:S = {[Data from fluid phase AP activation experiments  and rabbc assays –59  was minimized with respect to x using the fminbnd function in MATLAB R2018b, with options TolX and TolFun set to 0.01 and 0.5, respectively. Due to computational complexity, the parameters were optimized with an iterative approach. At each iteration, all parameters were individually fitted in a space ±7 orders of magnitude around the initial value; the parameter producing the lowest objective function value was updated in the model. The procedure was repeated until improvement in the objective function was below 1%. The choice of this approach is discussed below.A fundamental assay of complement research involves the study of AP activation in the fluid phase by the spontaneous hydrolysis of C3. Various experimental setups have been described in the literature ,38,61–64kp,C3bH,surf). Initial cell concentration, serum dilution and readout time were set to match the reported experimental conditions . ODEs were implemented and simulated in the SimBiology toolbox of MATLAB software version R2018b . Unless stated otherwise, parameters were fitted using the lsqcurvefit function with default options as implemented in MATLAB R2018b.Data from publications was digitized with the 2O)Bb), and the terminal activity (association of C6 to complex C3bBbC3bC5b). All results presented below were generated with the final model parameterization. Two of the final estimates were greater than the diffusion limit of protein-protein association of 109 M-1s-1. These two parameters were linked to negative regulators of the pathway (association of CD50 to C5b9 and association of DAF to C3 convertase) occurring on the surface of erythrocytes. These reactions likely involve co-localization or clustering of inhibitors to pre-formed complement complexes and occur on the 2D cell surface rather than in 3D space and are therefore not limited by the diffusion limit.The final model consisted of 226 reactions, of which 111 described the AP, 112 described complement protein turnover and 3 were related to eculizumab. In total there were 121 parameters of which 70 were kinetic rate constants directly related to complement protein interactions and enzymatic reactions within the AP, 39 to non-AP related synthesis and elimination reactions, and 2 to eculizumab binding. The remaining 10 parameters were used to parameterize e.g. hemolysis and the dynamics of the hematological biomarkers. A preliminary assessment of model performance with the parameterization by Zewde et al. [SSRSum , while inhibition of DAF does not produce any hemolysis ,59. The We simulated the pairwise inhibition of AP regulators following the experimental setup of Ferreira and co-workers  Fig 5B)Fig 5B). Replicating in vitro measurements of PNH erythrocyte lysis inhibition by eculizumab in acidified serum , the modThe synthesis rates of complement proteins, estimated assuming negligible activation in healthy individuals, and the corresponding fractional catabolic rates (FCR) are reported in The hemoglobin levels in PNH type 3 patients were used to parameterize the rate of MAC-mediated hemolysis. The predicted LDH and hematocrit levels in PNH type 2 patients and healthy individuals matched very well the ranges reported in the literature .We explored the in vivo effects of eculizumab on the hemoglobin levels in PNH patients . The modComplement is becoming increasingly recognized as a major driver of several common and rare diseases such as PNH, aHUS and AMD  affectinThe model herein presented builds upon previous works offering a mechanistic description of the biochemical interactions involved in AP regulation and activation, in particular the work of Zewde et al. . We exteIn our efforts to study the behavior of the pathway through in silico predictions, we first honed in on a well characterized step of the AP cascade: the spontaneous hydrolysis of the thioester group of the C3 protein. This mechanism represents the initial step in AP activation, followed by the formation of C3 proconvertase and convertase complexes and the concomitant cleavage of C3 into C3a and C3b. It has been described that pre-incubation of serum samples at 37°C causes a time-dependent decrease of hemolytic activity . This efKm decreased up to ~28-fold with an increase in density of C5 convertases on the cell surface, a mechanism not included in the present version of the model. While developing the model, we also found that the time of readout is a critical parameter in the model, as observed in the underprediction of the 5-minute lysis experiment  is a frequently used screening test for complement abnormalities, and one of the standard assays to establish dose-response relationships in clinical trials. This method relies on the hemolysis of unprotected rabbit erythrocytes upon the addition of human serum. The model largely reproduced the rapid kinetics of hemolysis as well as the degree of lysis as a function of the concentration of serum and various complement factors . We founperiment . Here itperiment . In sum,kp,C3b,surface) were reduced. The FB synthesis rate remained nonetheless 7-fold faster than reported in literature  of complement proteins so as to mimic AP homeostasis. Background activity is known to differ, the pathway being more reactive or partly activated in vitro. In fact, sample processing and assay conditions have been shown to influence the level of complement proteins significantly. For instance, it has been reported that thawing blood samples for one hour at room temperature versus at 37°C can lead to an over 200-fold increase . Also, tterature , suggestTo establish the clinical applicability of the AP model, we examined PNH disease as a case study. In PNH, erythrocytes lack plasma membrane proteins imparting protection against complement attack, a defect that leads to chronic hemolysis. Hematological laboratory values such as hemoglobin, hematocrit, and LDH levels are therefore used in the clinical management of the disease. The development of eculizumab, a monoclonal antibody directed against C5, has resulted in dramatic improvements of survival and reduction in complications. The model was shown to predict the baseline levels of common hematological markers  in healthy subjects and PNH patients , the effIn conclusion, the model herein presented can reproduce in vitro and in vivo AP activation and AP-mediated hemolysis. It provides a mechanistic and quantitative framework to guide the design of studies and integrate experimental and clinical data. It may prove useful for testing novel therapeutic hypotheses, namely selecting targets for pharmacological intervention and predicting the efficacy of drug candidates. While we believe the model is a state-of-the-art representation of AP biochemistry, future studies might indicate that the model assumptions and parameterization should be revisited. The model could also be extended to other cell types, such as bacteria, allowing the use of a wider set of experimental information. Learn-and-confirm cycles between simulation and experimentation can help identify gaps in our understanding of the pathway and lead to future improvements in the model.S1 FigLDHmax = 1495 U L-1, HLDH50 = 7.94 g dL-1, and LDH0 = 296 U L-1.Reported measurements of blood LDH and hemoglobin levels in 30 PNH patients treated with eculizumab (symbols) . LDH lev(TIF)Click here for additional data file.S2 FigSSRSum, The iterative optimization of parameters led to successive improvements in the objective function and an increasing convergence between model and data. The figure shows the fitted parameter at each iteration together with the associated change in sum of squared residuals SSRSum, . The est(TIF)Click here for additional data file.S3 FigSSRSum relative to the one obtained with the final parameterization was calculated. Boxes indicate parameters that were optimized during the iterative parameter optimization (Kinetic rate constants were decreased (blue) or increased (red) by 1, 5, 10 and 20% (light to dark) around their final estimate and the change in mization , S2 Fig.(TIF)Click here for additional data file.S4 Fig11 cells/L which corresponds to a commonly used experimental setup  or increased (red) by 1, 5, 10 and 20% (light to dark), and the change of terminal pathway activation as quantified by MAC formation in a standard rabbit erythrocyte hemolysis assay was calculated. Experimental parameters used were 30 min readout time, 20% serum and 1*10al setup .(TIF)Click here for additional data file.S1 TableDescription of literature sources and their use in model development.(PDF)Click here for additional data file.S2 TableInitial conditions of the differential equations describing the change in protein concentrations over time. For in vivo simulations, these initial values coincide with the steady state levels. For unlisted proteins and complexes, the initial concentration was assumed equal to 0 or to their steady state level when simulating the in vitro or in vivo setting, respectively.(PDF)Click here for additional data file.S3 TableCell species, publication, initial cell concentration, readout time and serum concentration for each of the simulated hemolytic experiments.(PDF)Click here for additional data file.S4 TableEstimation of the systemic half-life of complement proteins based on their molecular weight as described in (PDF)Click here for additional data file.S1 AppendixList of biochemical reactions of the AP, complement protein turnover reactions and reactions involving eculizumab.(PDF)Click here for additional data file.S2 AppendixList of model parameters.(PDF)Click here for additional data file.S3 AppendixDerivation of quantitative relationship between MAC formation and hemolysis.(PDF)Click here for additional data file.S4 AppendixQuantitative relationship between molecular size and half-life.(PDF)Click here for additional data file.


The hardness of HBCS increases gradually with the increase of Mo content due to the solid solution strengthening and the refinement of M2B. It can be found that all the samples exhibit quasi-cleavage, but the impact toughness increases firstly and reaches the maximum value when the concentration of Mo is 2.10 wt.%, which is the result of the dispersive distribution of M2B rather than the original fish-bone M2B. Subsequently, the impact toughness begins to decrease as the concentration of Mo further increases because of the extensive formation of grainy Mo-rich M2B at the grain boundary. Meanwhile, the wear results reveal that the average friction coefficient and wear ratio decrease with the increase of Mo content, and the wear mechanism changes from abrasive wear and adhesive wear to abrasive wear when the concentration of Mo exceeds 2.10 wt.%.The microstructure evolution, mechanical properties, and tribological properties of high boron cast steel (HBCS) with various Mo concentrations are investigated. The results indicate that Mo addition can significantly modify the microstructure and enhance the comprehensive properties. With the increase of Mo concentration, borides change from the original fish-bone Fe-rich and Cr-rich M Wear, as one of the most common failure modes of metal materials, has received much attention due to its ubiquity in industrial fields and consequential tremendous economic loss ,2,3. Mor3C and M7C3 to MC and M2C  since, generally speaking, the wear resistance of materials is proportional to the hardness of the materials. Unfortunately, to achieve better wear resistance in this way, on the one hand, a large amount of carbon is needed for forming the carbide reinforcing phases, consequently resulting in the formation of the high-carbon martensitic matrix with poor toughness  direction, leading to a strong susceptibility to cracking, which significantly brings down the toughness of HBCS  direction [2B. It could be concluded that the fracture of all four groups of samples was quasi-cleavage. In addition, the cleavage planes in a large size observed in 2B was harmful to the impact toughness of HBCS. Because of the refinement of M2B and the elimination of fish-bone M2B, the large-sized cleavage planes were replaced by a series of small cleavage planes, as shown in 2B at grain boundary reduced the continuity of the matrix, which led to the decrease of plastic deformation and the reduction of impact toughness. Moreover, the decline of the fracture toughness of M2B when the Mo concentration reached 2.86 wt.% as mentioned above, accelerated the rate of crack initiation and propagation in M2B. More cracks are observed in the magnification in The impact fracture morphology is shown in irection , which lThe friction coefficient of the samples is shown in The wear ratio calculated by Equation (1) and the average friction coefficient in the steady-wear stage are shown in 2B, which enhanced the wear resistance effectively. Only a few M2B collapsed and broke down under the vertical force due to the low toughness and were peeled off from the surface, leaving pits of different sizes. The wear mechanism of alloys A2 and A3 was abrasive wear. The increase of the matrix hardness caused by Mo addition greatly promoted the improvement of wear resistance.The wear morphology was measured by SEM, as shown in (1)2B. Moreover, with the increase of Mo concentration, the morphology of borides changed from the fish-bone Fe-rich M2B to cluster-like and blocky Cr-rich M2B and grainy Mo-rich M2B. Meanwhile, borides were greatly refined.Mo promoted the formation of Mo-rich and Cr-rich M(2)2B.The hardness of HBCS increased with the increase of Mo content, which was mainly affected by the solid solution strengthening of Mo and the refinement of M(3)2B and the refinement of M2B were responsible for the improvement of impact toughness. However, the extensive formation of Mo-rich M2B at the grain boundary and the decrease of fracture toughness of M2B greatly damaged the impact toughness when the Mo content was 2.86 wt.%.Although all four alloys showed quasi-cleavage, the impact toughness rose firstly, then reduced with the increase of Mo content, and reached its maximum value at 2.10 wt.% Mo. The decrease of fish-bone M(4)The average friction coefficient and wear ratio both showed a descending trend with the increasing Mo content. The wear mechanism changed from abrasive wear and adhesive wear to abrasive wear when the content of Mo exceeded 2.10 wt.% due to the better resistance of the matrix to the abrasive.The microstructure evolution and properties of HBCS with different Mo contents were systematically studied. The main results are listed as follows:


In order to improve the joint of two dissimilar metals, a zinc interlayer was inserted between the Mg alloy and Cu, and the effects of the thickness of the Zn interlayer on the microstructure and properties of the joint were studied. The fused zone consisted of Cu2Mg and MgZn, and, according to first-principles calculation, in the same energy range, the area enclosed by the density of the state curve of MgZn was larger than that of Cu2Mg. Hence, the bonding ability of MgZn was better than that of Cu2Mg, and MgZn improved the strength of the welded joint. The most advantageous thickness of the Zn interlayer was 0.1 mm, and the shear strength was 48.15 MPa that was 161% higher than that of the directly welded Mg/Cu joint.During pulsed laser welding of AZ 31B magnesium (Mg) alloy and T2 pure copper (Cu), Cu In many engineering applications, multiple metals are required ,2. For e5Zn8.AZ31B Mg alloy and T2 Cu are typically welded by solid-phase diffusion welding . By adjuIn spite of these aforementioned and other studies, there are still problems with welding of dissimilar metal systems, such as Mg/Cu, and the use of laser welding of Mg/Cu has not been investigated extensively. Herein, a Zn foil was used as an interlayer for laser welding of Mg/Cu, and the effects of the Zn interlayer thickness were evaluated systematically. In addition to experiments, the first-principles calculation was carried out to analyze the electronic structure and properties of the joint, as well as strengthening mechanism.The base metal was the AZ31B Mg alloy with a thickness of 1 mm and lateral dimensions of 100 mm × 50 mm, and the T2 pure Cu plate had a thickness of 0.5 mm. The composition of the two metals is shown in The welding equipment consisted of a pulsed Nd: YAG laser  with an instantaneous laser power of 2.5 kW, a welding rate of 1.4 mm/s, single-point energy of 19.31 J, and an Ar gas flow rate of 10 L/min. The laser beam diameter was 0.1 mm. The Zn foil was inserted between the Mg plate and Cu plate, as shown in After welding, the samples were embedded in epoxy resin, ground, and polished. The microstructure was observed by optical microscopy , scanning electron microscopy , and transmission electron microscopy . The elemental distributions at the interface and fracture surface were determined by energy-dispersive X-ray spectrometry (EDX). Vickers hardness measurement  was performed across the laser-welded joints with 0.1 mm Zn interlayer under a test load of 100 g and a dwell time of 10 s. The shear strength was determined on the universal testing machine for materials  at a rate of 0.05 mm/min in triplicate to obtain the average. The load was increased during the test and then decreased suddenly.2Mg and MgZn was constructed, and the bonding ability was calculated. The CASTEP module in Materials Studio software was implemented to perform generalized gradient approximation (GGA) on the crystal structure, and the equation was self-consistently solved by Kohn–Sham. Before the calculation, the unit cell constant of the compounds and each atomic lattice were fully relaxed until the unit cell energy converged to a fixed value. The results were not related to the spin effects.First-principles calculation was conducted based on the density-functional theory and supersoft pseudopotential method ,21. The The welded joints with Zn interlayers of different thicknesses are shown in 2Cu was formed at point 1 and Cu2Mg at point 2. The intermetallic compounds—Mg2Cu and Cu2Mg—were produced during direct welding of Mg/Cu [2Cu was usually generated at the top of the joint, and Cu2Mg at the edge. Cu2Mg + MgZn was detected from point 3, and MgZn was observed from point 4. Zn prevented the formation of some MgCu intermetallic compounds. According to the phase diagram of the Mg–Zn binary alloy [The EDX results of the four points shown in of Mg/Cu . Mg2Cu wry alloy , the eut2Mg and MgZn, respectively, and Zn could react with Mg and inhibit the formation of Mg/Cu compounds.To identify the phases formed in the fused zone in the joint with the Zn interlayer, TEM was performed. 2Mg and MgZn were constructed, and the electronic structures were calculated. The density of state (DOS) map was the visualization result of band. Because the electronic energy levels (orbits) were very dense, a standard continuous energy band was formed. DOS was to summarize the distribution of energy levels. A molecule is formed by two atoms. Two atomic orbitals form two molecular orbitals according to a certain relationship, and two molecular orbitals form two energy bands. For bonding orbitals, it is mainly the atomic orbitals of atoms with higher electronegativity, and the atomic orbitals of other atoms are doped, so the energy band can’t show the contribution of a specific orbit, but the density of state diagram can get the contribution of a specific orbit. The density of state (DOS) can be divided into the local density of state (LDOS) and the partial density of state (PDOS). The LDOS refers to the contribution of the electronic states of each atom to the total density of the state diagram. The PDOS refers to the further resolution of these contributions according to the angular momentum . It is determined that the main peak of the density of the state is specifically from the contribution of electronic states, such as s, p, d, or f. According to the PDOS, it can not only analyze the bonding but also analyze where the electron is. The results of Cu2Mg are presented in 2Mg was relatively scattered, and the DOS of the p orbital showed a large peak. The energy of the electrons contributing to bonding was mainly concentrated in the range between −50 eV and −40 eV and mainly came from the contributions of valence electrons of Mg (P), Mg (d), and Cu (d). However, the contribution of valence electrons of Mg (s) and Cu (P) was small. 2Mg, but it showed two higher peaks. The vertical coordinate in the density of the state diagram was larger. According to the total density of the state diagram of the two compounds, the area under the density of the state curve was calculated by origin integral, and the number of bonding electrons of the two compounds could be obtained. In the range of −80 ev to 20 ev, the enclosure area of Cu2Mg was 111.942, while that of MgZn was 1177.618. Cu2Mg crystal structure had 24 atoms, while the MgZn crystal structure had 47 atoms. The bonding electron number of Cu2Mg was 4.664, and that of MgZn was 25.055. It was found that the number of bonding electrons of MgZn was much larger than that of Cu2Mg, which indicated that the interaction between valence electrons of MgZn was stronger, and the structure was more stable. In the same energy range, the area enclosed by the density of the state curve of MgZn was larger than that of Cu2Mg and, hence, the bonding ability of MgZn was better than that of Cu2Mg [2Mg, and the strength of the welded joint was improved.The first-principles calculation was conducted based on the DFT and super soft pseudopotential method. The crystal structures of CuThe shear strength of the joints is shown in 2Cu and Cu2Mg—were produced during direct welding of Mg/Cu. Mg2Cu was usually generated at the top of the joint, whereas Cu2Mg was generated at the edge. Cu2Mg and MgZn were formed in the fused zone in the joint with Zn as the interlayer, and Zn prevented the formation of some Mg/Cu intermetallic compounds. The bonding ability of MgZn was greater than that of Cu2Mg, according to first-principles calculation. Experimentally, the shear strength of the welded joint with the 0.1 mm thick Zn interlayer was 48.15 MPa, which was 161% higher than that of the directly welded Mg/Cu joint.Strong joints were obtained by pulsed laser welding of Mg/Cu by inserting a 0.1 mm thick Zn interlayer. The optimal welding parameters were instantaneous laser power of 2.5 kW, a welding rate of 1.4 mm/s, single-point energy of 19.31 J, and an Ar gas flow rate of 10 L/min. Intermetallic compounds—Mg


Furthermore, the fiber reinforcement index λ quantifies the enhancement by the fibers. Both estimation results indicated that the UCS values were estimated accurately at curing times of 3, 7 and 28 days in this study. Additionally, the estimation models could be used to guide the strength design of fiber-reinforced CPB. Besides this, the results showed that fiber-reinforced CPB can be used more widely in mine backfills and meets the requirements of controlled low-strength material (CLSM) for broader applications.This experimental investigation was conducted to research the properties of polypropylene (PP) fiber-reinforced cemented paste backfill (CPB). The unconfined compressive strength (UCS) of the fiber-reinforced CPB showed a significant improvement with average UCS increase ratios of 141.07%, 57.62% and 63.17% at 3, 7 and 28 days, respectively. The macroscopic failure mode and SEM analysis indicated that fibers prevented the formation of large tensile and shear cracks during the pull-out and pull-off failure modes. A linear fitting function for the UCS at a curing time of 3 days and two polynomial fitting functions for the UCS at curing times of 7 and 28 days were established to characterize the relationship between the UCS of the fiber-reinforced and unreinforced CPB. Moreover, based on composite mechanics, nonlinear models related to the UCS and fiber reinforcement index were obtained. The estimated functions containing the fiber reinforcement index  The treatment of mine tailings has become a hot topic in mining engineering research in recent years due to the potential environmental hazards as well as recovery value prospects ,2. CemenFiber-reinforced cement-based materials are becoming more popular in civil and structural engineering because they are used to enhance the strengths of soils and structures by the high strength and ductility characteristics of the fiber material ,23,24,25fcf and cf are the UCS of the fiber-reinforced concrete and unreinforced concrete, respectively; ifλ is the fiber reinforcement index of the ith fiber; ifρ is the volume fraction of the ith fiber, vol.%; ifl/ifd is the aspect ratio of the ith fiber; ifl is the length of the ith fiber; ifd is the diameter of the ith fiber, mm; α is the influence factor of the fiber; i is the number of types of added fiber.In addition, due to differences in the properties of the engineering materials, such as the type of fiber, cement and tailing material, the effects of fiber reinforcement are different in their respective engineering applications, and their increases in structural strength range from dozens to hundreds. ,32. In pBased on the above considerations, experimental and nonlinear model studies were conducted to investigate the UCS of CPB. Firstly, the effect of fibers on the UCS of CPB was investigated through experimental data and macroscopic failure mode analysis. Then, the UCS of the fiber-reinforced CPB as a function of the UCS of the unreinforced CPB was studied with different fitting methods. Moreover, the effects on the CPB and failure modes of fibers were described with data comparison and microscopic analysis, and nonlinear modes were established based on composite mechanics to estimate the UCS of fiber-reinforced CPB and quantify the reinforcement by the fibers. Finally, the application prospects of fiber-reinforced CPB were discussed.D50 = 25.31 μm, and more than 47.15% of the particles had a size that was smaller than 20 µm, which indicated that the tailings belonged to the medium particles [Tailings were collected in the Fan Kou lead-zinc mine in China. The particle size distributions of the tailings and cement were determined by a LS particle size analyzer . Particle diameter is determined by analyzing the light scattering and diffraction characteristics caused by particles. The size distribution of the tailings could be characterized by a median diameter of articles . Portlanarticles  and X-raL16 (44) based on orthogonal table was designed to investigate the effects of fibers and cement on the strength properties of CPB. The four factors used were the cement content (A), solid mass concentration (B), fiber content (C) and fiber length (D), with four levels for each factor as follows: 13 wt.% (A1), 10 wt.% (A2), 8 wt.% (A3) and 7 wt.% (A4); 60 wt.% (B1), 62 wt.% (B2), 64 wt.% (B3) and 66 wt.% (B4); 0.05 vol.% (C1), 0.11 vol.% (C2), 0.16 vol.% (C3) and 0.22 vol.% (C4); and 3 mm (D1), 6 mm (D2), 9 mm (D3) and 12 mm (D4), respectively. The size of the specimens was 50 mm in terms of diameter and 100 mm in terms of height, and triple specimens were prepared for each mixture at different curing ages, as shown in Orthogonal tests are an effective method of multi-factor analysis with a minimum of the computational load designed based on an orthogonal table. This method conducts tests by selecting a suitable number of representative test cases from many test data and has the advantages of even dispersal and neat comparability with the minimized trials for a complete analysis ,39. To sAs shown in ik represents the average of all UCSfiber-reinforced under level i, and jR represents the range  [eR is the UCS increase ratio, %; fiberσ is the UCS of the fiber-reinforced CPB, MPa; and no-fiberσ is the UCS of the unreinforced CPB, MPa.For the fiber-reinforced CPB, the analysis of orthogonal test results is shown in  values) . The sigThe macroscopic failure modes of the eight CPB specimens are listed in R2 = 0.9562 and R2 = 0.9600 for the fiber-reinforced and unreinforced CPB. The R2 is defined in Equation (5), and the closer R2 is to 1, the better the formula fits [y is the UCS of the CPB, MPa, and x is the cement content, wt.%.n is the number of data sets; ith data set.The cement content played a significant role in enhancing the strength of the CPB. Therefore, in this study, the effects of eight different cement contents  on the UCS of the fiber-reinforced and unreinforced CPB were studied. Some of the data have been published in previous studies . Figure ula fits ,44,45. TR2 = 0.6405 at a curing time of 3 days. At 7 and 28 days of curing, the four fitting formulas all had high fitting accuracies with the goodness of fit values greater than 0.85 and 0.72, respectively. The best fitting accuracy at 7 and 28 days of curing was obtained through the polynomial fitting, with R2 values of 0.9086 and 0.8766, respectively. Therefore, the three corresponding formulas in A total of 96 sets of UCS data of fiber-reinforced and unreinforced CPB are shown in MSE) and goodness of fit (R2) values were implemented as indices of the accuracy of evaluation. Contrary to R2, the closer MSE is to zero, the higher the accuracy [MSE can be calculated by Equation (6). As shown in MSE and R2 values of the fit between the estimated value and measured value of the fiber-reinforced CPB at 3 days of curing were 0.0638 and 0.6011, respectively. The discrete distribution of data points near the ideal fit line indicated that the UCS estimation was not very ideal. However, the UCSs of the fiber-reinforced CPB at 7 and 28 days of curing showed good estimation results. MSE and R2 values of the UCS at 7 days of curing were 0.0118 and 0.9086, respectively. The MSE and R2 of the UCS at a curing time of 28 days were 0.0365 and 0.8766, respectively.accuracy . The MSEThe analysis’ results demonstrated that the UCS of the fiber-reinforced CPB after 3 days of curing was accurately estimated and represents a comprehensive influence of hydration reaction intensity, fiber reinforcement and sulfate attack. Thus, it could be used to estimate the material properties.In λ), which can reflect the comprehensive characteristics of the fiber, is proposed by considering a positive hybrid effect as follows:σfiber is the UCS of the fiber-reinforced CPB, MPa; σno-fiber is the UCS of the unreinforced CPB, MPa; λ is the PP fiber reinforcement index as shown in V is the volume fraction of the PP fiber, vol.%; l/d is the aspect ratio of the PP fiber; l is the length of the PP fiber, d is the diameter of the PP fiber, mm; α is the influence factor of the fiber; β is a constant.From the above analysis, the PP fiber had a significant reinforcement effect on the UCS of the CPB, and the effect was different for different fiber contents and fiber lengths. Therefore, a UCS calculation equation that could quantify the fiber reinforcement needed to be developed. The fiber-reinforced CPB can be considered a composite material composed of multiple phases. It is assumed that the fibers are evenly distributed in the CPB matrix, and the fiber-reinforced CPB is anisotropic material. Its mechanical properties can be considered as the result of the superposition of the mechanical properties of the fibers and unreinforced CPB, and this method has been used to evaluate the UCS of concrete reinforced by steel fibers . Based oR2 = 0.5304. In addition, as with the quantitative representation of the fiber reinforcement index (λ), the greater the value of constant α, the greater the contribution of the fibers to the UCS of the CPB. As shown in α were 0.2072, 0.0408 and 0.0725 at 3, 7 and 28 days of curing, respectively. The highest α value at a curing time of 3 days indicates that fibers played a more fully reinforcing role at this curing age. This result is also consistent with the conclusion that the UCS enhancement ratio is higher at 3 days of curing, as summarized in Then, MATLAB was used to establish the fiber-reinforced UCS estimation equation, and three surface equations related to the UCS and fiber reinforcement index were obtained, as shown in MSE values at 3, 7 and 28 days of curing were 0.0396, 0.0131 and 0.0367, respectively. The R2 values at 3, 7 and 28 days of curing were 0.5304, 0.9016 and 0.8497, respectively. Both the MSE and R2 indicated that the fitting formula in 3 and 5.37–10.15 $/m3, respectively. For general mines in China, the cost for producing backfill is a large expenditure, and there will be an increase in cost with fiber-adding when the proportion of CPB is not changed. For example, take the data of mixture T2 shown in 3 to 8.93 $/m3, with an increased ratio of 12.61%. If the aim is to keep the UCS as unreinforced CPB, the addition of fiber can reduce the consumption of cement, and the cost to prepare CPB with fibers is cheaper than that without fibers. Take the UCS of CPB mixture T14 with reducing cement consumption 6 wt.% and increasing fiber content 0.16 vol.%. It is basically the same as that of mixture T2  of CPB was calculated and represented in Comparative analysis of the changes of UCS and materials cost after adding PP fiber with different proportions in re T2 in , and theIt is reasonable and effective to apply low strength, fiber-reinforced CPB as a kind of controlled low-strength material (CLSM). CLSM is a cement-based material mainly used for backfilling with a UCS below 8.3 MPa, and the UCS usually varies depending on project requirements ,48,49, bThis paper mainly studied the utilization of lead-zinc tailings as raw materials of CPB, focusing on the effect of adding PP fiber on the properties of CPB. Many research results have been achieved in this study, but there are still some limitations to the CPB application. First of all, there are many kinds of fibers, such as steel, glass and carbon fibers, which have been used in the field of concrete ,52. It i(1)The CPB prepared with a lower amount of cement in this study had a lower UCS, and the UCS of the unreinforced CPB was lower than 0.4 MPa. The UCS of CPB was improved significantly but did not exceed 1.0 MPa. Besides, increasing the cement content could effectively improve the strength of the CPB, and the fiber and cement played complementary roles in enhancing the strength of the CPB.(2)In this study, the expansion of CPB caused by sulfate attack due to the fibers resulted in the material not being able to fully exert its pressure resistance effect after 3 days of curing. The macroscopic failure modes indicated that the fibers could prevent the formation of large tensile cracks and shear cracks. The SEM tests further showed that the fibers mainly enhanced the UCS of the CPB with pull-out and pull-off failure modes.(3)λ.The linear and polynomial fitting function could characterize the relationship between the UCS of the fiber-reinforced and unreinforced CPB at the three different curing ages. The nonlinear UCS estimation equation of the fiber-reinforced CPB based on composite mechanics could reliably be used to estimate the UCS and more clearly quantify the reinforcement effect of the fibers with fiber reinforcement index (4)λ value indicated that fibers played a more fully reinforcing role at 3 day curing age.Both estimation results indicated that the UCS of CPB could be estimated accurately. Furthermore, the high fiber reinforcement index In this study, a series of experimental investigations were conducted to investigate the reinforcement effect of fibers on UCS of CPB, and nonlinear UCS fitting formulas were proposed to estimate the UCS of the fiber-reinforced CPB. The conclusions can be summarized as follows:Based on the above considerations, the fiber-reinforced CPB can be more widely used in mine backfills. The latter is also an important direction for future research of wide-ranging material applications.


First cases of COVID-19 were reported from Wuhan, China, in December 2019, and it progressed rapidly. On 30 January, WHO declared the new disease as a PHEIC, then as a Pandemic on 11 March. By mid-March, the virus spread widely; Djibouti was not spared and was hit by the pandemic with the first case detected on 17 March. Djibouti worked with WHO and other partners to develop a preparedness and response plan, and implemented a series of intervention measures. MoH together with its civilian and military partners, closely followed WHO recommended strategy based on four pillars: testing, isolating, early case management, and contact tracing. From 17 March to 16 May, Djibouti performed the highest per capita tests in Africa and isolated, treated and traced the contacts of each positive case, which allowed for a rapid control of the epidemic. COVID-19 data included in this study was collected through MoH Djibouti during the period from 17 March to 16 May 2020. A total of 1,401 confirmed cases of COVID-19 were included in the study with 4 related deaths (CFR: 0.3%) and an attack rate of 0.15%. Males represented (68.4%) of the cases, with the age group 31–45 years old (34.2%) as the most affected. Djibouti conducted 17,532 tests, and was considered as a champion for COVID-19 testing in Africa with 18.2 tests per 1000 habitant. All positive cases were isolated, treated and had their contacts traced, which led to early and proactive diagnosis of cases and in turn yielded up to 95–98% asymptomatic cases. Recoveries reached 69% of the infected cases with R0 (0.91). The virus was detected in 4 regions in the country, with the highest percentage in the capital (83%). Djibouti responded to COVID-19 pandemic following an efficient and effective strategy, using a strong collaboration between civilian and military health assets that increased the response capacities of the country. Partnership, coordination, solidarity, proactivity and commitment were the pillars to confront COVID-19 pandemic. Since the first reports of emergence of the coronavirus disease 2019 (COVID-19) in Wuhan the capital city of Hubei province, China, in December 2019, the disease has progressed very rapidly . COVID-1COVID-19 affected some countries in a more severe course than others . As of 1Although Africa is considered as the most vulnerable continent considering the overall weaker health systems and infrastructure, the African countries were the last ones to be hit by the pandemic . Egypt rDjibouti was not spared by the spread of the COVID-19 pandemic. Situated in the horn of Africa, with a surface area of 23,200 square kilometers (2018)  and a poSince the first case was detected on 17 March up to 16 May 2020, Djibouti reported 1,401 confirmed COVID-19 cases including 4 deaths  with a cSince March 2020, the government of Djibouti pursued effective and strict policies starting by the closure of land borders, the port and the airport on 18 March 2020 . Many otAs the emergence of COVID-19 represented a threat to the global health system, it was important to conduct this study to examine and analyze the epidemiology of the coronavirus disease (COVID-19) in Djibouti, and to explain how successful was the preparedness and response strategy, followed by the civil and military health authorities and their partners in Djibouti, during the first two months of the response to the pandemic in the country from 17 March to 16 May 2020.The strategy adopted by the Ministry of Health was and its partners was perfectly in line with WHO recommendations based on four pillars: testing, isolating, early case management, and contact tracing.The oropharyngeal and nasopharyngeal samples, as well as, sputum samples were collected from COVID-19 suspected patients and their contacts by a team of paramedics trained for sample collecting at the Hospital Bouffard.The samples were tested by real time polymerase chain reaction (RT-PCR) machines procured by WHO and also through MoH mechanisms. The reagents used were WHO approved (Sarbecov E-GENE Plus EAV control kits).In close collaboration between the civil and military health authorities, a protocol for isolation and case management was developed and implemented first at hospital Bouffard where nearly 50 beds were dedicated to COVID-19 case management. A second center was opened in Arta region using the premises of a hospital used by the social security department .The Police and Gendarmerie’s medical services were in charge of tracing, quarantining, testing and isolating all the close contacts of each confirmed case.All coronavirus disease (COVID-19) laboratory-confirmed cases reported officially by the Ministry of Health of Djibouti during the study period. A case definition for the COVID-19 was identified by the Ministry of Health of Djibouti and it was in line with the WHO case definition during the period of the study.1) a patient with acute respiratory infection (of sudden onset) or at least one of the following symptoms: cough, fever, shortness of breath AND without an etiology explaining the clinical presentation AND with a history of traveling or residence in a country/region reporting local or community transmission during the 14 days prior to the onset of symptoms; OR 2) a patient with acute respiratory illness AND who has been in close contact with a confirmed case of COVID-19 during the past 14 days prior to the onset of the symptoms; OR 3) a patient with severe acute respiratory infection, fever and at least one sign/symptom of respiratory illness  AND requiring hospitalization (Severe Acute Respiratory Infection—SARI) AND without any etiology that explains the clinical presentation.Any person, symptomatic or not, with a lab-confirmed specimen by RT-PCR for the infection of COVID-19, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A person who, during the 24 hours prior to the onset of symptoms of a confirmed case, shared the same living space  or had direct face-to-face contact within 1 meter or less of the case and/or for more than 15 minutes, in a discussion; close friends; class or office mates; close to a case in a transport for an extended period of time; a person providing care of a confirmed case or laboratory personnel handling specimens of a confirmed case, in the absence of adequate equipment of protection.Data of COVID-19 patients reported by the Ministry of Health of Djibouti for two months were collected and included in the study. Since the first case of COVID-19 was reported in Djibouti on 17 March 2020 up to 16 May 2020.All COVID-19 data used in this study was collected through the epidemiological surveillance system of the Ministry of Health of Djibouti and retrieved through the daily communiqué developed and published by the Ministry of Health of Djibouti , as wellSince the beginning of the COVID-19 pandemic, the Ministry of Health of Djibouti identified the laboratory of Hospital Bouffard, situated in the capital, Djibouti-ville, as the only laboratory of reference for the testing and confirmation of COVID-19 cases in the country. Military and civilian laboratory technicians worked together under the supervision of a medical biology specialist from the private sector contracted by the MoH.The swabs, were collected from the COVID-19 suspected patients and from the contacts of COVID-19 positive cases, during the contact tracing procedure, to get tested by RT-PCR following the WHO guidelines for laboratory confirmation of the emerging disease during the study period .The collected COVID-19 data from Djibouti was revised, tabulated and entered into a PC Excel file (Microsoft Office). Data cleaning and quality checking were performed. The epidemiological and demographic characteristics were summarized in this study. A P-value less than 0.05 was considered statistically significant. Further data analysis was conducted by epidemiological week against the number of COVID-19 positive cases over the study period to show the coronavirus disease peak in the country, as well as, the positivity rate. R naught (R0) was calculated per week and for the whole period of the study.This study was conducted using publicly anonymous online available data published by the Ministry of Health of Djibouti; therefore, no ethical approval was needed.From 17 March to 16 May 2020, 1,401 positive COVID-19 cases were reported by the Ministry of Health in Djibouti including 4 deaths with a case fatality rate (CFR) of 0.3% and an attack rate of 0.15%. Twenty-eight cases were primary cases and the rest were contacts of positive cases that were found positive during the aggressive and proactive contact tracing exercise. The peak of COVID-19 pandemic in Djibouti started during the first week of April 2020 and the number of cases started to decline during the third week of the same month .The period of this study resides between the epidemiological week number 12 (15–21 March 2020) and the epidemiological week number 20 (10–16 May 2020) [The demographic characteristics of COVID-19 cases during the study period in Djibouti shows that male gender dominated the reported cases by 68.4% (958) of the lab-confirmed cases in the country. During the study period, the highest age group affected by the emerging zoonotic virus was the age group 31–45 years old with 34.2% (479) of the cases followed by the age group 16–30 years old with 33.3% (466) of the cases .The response strategy, based on the four pillars, followed by the Ministry of Health of Djibouti during the study period, along with the treatment protocol agreed upon in the National Action Plan for preparedness and response for COVID -19  showed eThe figure also shows the progression of the basic reproduction number or the R naught (R0), which is an epidemiologic metric used to describe the contagiousness or transmissibility of infectious agents, by week. The highest reported R0 during the study period was during the epi week 13 (22–28 March 2020) with a value of 18. The weekly R naught varied during the study period from 0.3 to 18, with an overall R naught of 0.91 during the 9 weeks of the study.Primary COVID-19 cases in Djibouti represented 2% (28) of the reported cases in the country during the study period. Secondary cases and contacts of the contacts represented 98% (1373) of the cases . The lowCOVID-19 pandemic was reported in 4 out of 6 regions in the Republic of Djibouti. The affected regions were respectively: Djibouti-ville  with 83% (1157 cases) of the reported cases, Ali Sabieh with 10% (143 cases) of the cases, Arta with 6% (91 cases) of the cases and Dikhil with only 1% (10 cases) of the cases reported during the study period .This is a descriptive study of the epidemiology of COVID-19 cases reported in Djibouti during the first two months of the detection of the virus in the country. It explains the response strategy put and adopted by the Ministry of Health of Djibouti together with its civilian and military partners during the same period, in close collaboration with WHO country office, which was followed strictly during the period of confinement announced by the government in the country between 23 March and 16 May 2020 .The study findings show that the first peak of the COVID-19 pandemic in Djibouti started in the first week of April 2020 (epi week 15) and the number of cases started to decline during the third week of the month (epi week 18). Epi week 16 represented the top of the curve in Djibouti with 3,693 performed tests and with 631 positive cases detected, with a positivity rate of 17%. This is explained by the rise of the laboratory capacity to perform more tests per day, the detection of two clusters of COVID-19 in two hospitals during this period, one hospital in Djibouti-ville and the second in Ali Sabieh region , simultaThe results of gender differences in the patients of COVID-19 in Djibouti are conforming with the results in other studies conducted in different countries and regions showing that the number of male patients affected by COVID-19 is almost the double of female patients ,24. DjibDjibouti showed a high percentage of recoveries among COVID-19 infected patients, 69% (972), during the study period. This was explained by the strict strategy of testing every suspected case of COVID-19 and contact tracing for all contacts. The patients were isolated at a very early stage of the infection, most of them asymptomatic, and treated according to the protocol agreed upon by the case management committee in the country. According to the case management protocol, Hydroxychloroquine and Azithromycin were introduced to all isolated patients, since day 1 of isolation up to they tested negative, with two consecutive swabs, with at least a period of 48 hours between the tests .The mortality rate in Djibouti was one of the lowest in the region and globally, only 4 deaths (CFR: 0.3%). Deaths were elderly patients who were already in the Intensive Care Unit (ICU) even before being infected with COVID-19. They were recorded during the epi weeks: 15 (two deaths), 19 and 20 consecutively. Most of the cases of COVID-19 in Djibouti were contacts, 98% (1373), due to the strict interventions and decisions taken by the government of Djibouti of closing the airport, port and land borders, on 18 March 2020, just the following day of the detection of the first case in the country.Djibouti-ville, the capital, was the most affected region in the country with COVID-19 cases, 83% (1157). This is due to the residence of more than 70–75% of the population in the capital according to the latest Djibouti Statistical Yearbook 2019 . Ali SabIt is important to mention that during the study period, according to the data from the Ministry of Health (MoH), 95–98% of the reported COVID-19 cases were completely asymptomatic and mainly detected through the contact tracing procedure. Therefore, only 2–5% of the cases has symptoms, mainly with very mild symptoms; therefore, it was not significant to register the clinical features of the patients of the newly emerging disease by the MoH, during the study period, in the country.The strategy of response to the COVID-19 pandemic adopted by the government of Djibouti since the detection of the first case in the country up to the last day of the confinement, 16 May 2020, was based on four main pillars. These pillars were: 1) Testing every single COVID-19 suspected case according to the case definition, by taking the needed swabs for the PCR test; 2) Isolating all detected positive cases in a center of isolation prepared specifically for this reason by the government in Arta region; 3) Starting an early case management for all positive cases before even the development of symptoms; and 4) Conducting a strict contact tracing procedure for all contacts of the positive cases, testing them, and isolating those who were tested positive .This strategy permitted to protect Djibouti from having severe or critical cases of COVID-19 during the first two months of the circulation of the virus in the country. An objective that was targeted since the first day of the development of the preparedness and response plan due to the limited Intensive Care Unit (ICU) capacities in the country, as well as, the shortage in the human resources working for ICU.Regarding the laboratory, Djibouti built its laboratory capacity for detection and confirmation of COVID-19 cases using the PCR machine in a very short and limited time, almost less than one week. The country started by the capacity for testing 100 samples per day and reached the capacity of testing up to 2,000 samples per day in the first week of April 2020. The government designated the laboratory of Hospital Bouffard, in the capital, as the only reference laboratory for the testing of COVID-19 cases.During the study period, Djibouti conducted 17,532 tests for suspected COVID-19 cases as well as, the contacts detected through the contact tracing procedure, and the country was considered as a champion for COVID-19 tests in the African continent with the highest number of conducted tests per capita, 18.2 tests per 1000 habitant , up to 16 May 2020, considered higher than the triple of the average testing rates in the continent during the study period .The early preparedness for the newly emerging disease; the transparency; the interventions taken by and the commitment of the government of Djibouti to save the lives of their people; lead to an adequate and an ideal response to the pandemic in the country. A close collaboration between MoH, WHO and other health sector partners during the preparation of the National Action Plan for preparedness and response to the COVID-19 in Djibouti, developed as a first draft in February 2020, reviewed and updated in March 2020; had its efficient and effective results during the response.The preparedness and response plan for Djibouti was conforming with the WHO guidelines for surveillance strategies for COVID-19 human infection  publisheThe Ministry of Health of Djibouti understands that the coronavirus diseases (COVID-19) is still circulating in the country. Therefore, with the de-confinement started on 17 May 2020, a risk communication campaign was planned to sensitize the population to follow the barrier measures necessary to prevent a higher spread of the infection among the population. These measures include: 1) Frequent washing of hand with soap and water or an alcohol-based hand rub; 2) Preserving the physical distancing with others, either at home, at work or at any public place; and 3) Coughing or sneezing into a bended arm, or using a disposable tissue.This campaign and other measures taken by the government of Djibouti will help the country to confront the disease. The vigilance of the MoH and the technical, operational and logistical support from WHO and other partners involved in the health sector in the country are the pillars to mitigate the harmful effects of the pandemic on the Djiboutian population.Djibouti spent tremendous efforts to respond to the COVID-19 pandemic in the most adequate and efficient way, using the comparative advantages and harnessing the collaboration and collegiality between civilian and military health authorities that coordinated through the highest authorities in the country. The study described the epidemiological characteristics of the COVID-19 cases reported in the country and explained the response strategy followed by MoH and its partners. Conducting more studies is mandatory to deepen the understanding of the epidemiology of COVID-19, specifically, the clinical features of the emerging disease in the countries of the horn of Africa.It is important to acknowledge that partnership, coordination, solidarity, vigilance, proactivity and commitment were essential to confront COVID-19 pandemic in Djibouti, as the capacities of the health system were only optimal when resources from military and civilian health apparatus were brought together and worked alongside WHO and other UN agencies, as well as, national and international partners.S1 Dataset(XLSX)Click here for additional data file.


The reasons for the lower reporting of cases in females are unknown. Specific research and the implementation of a more sensitive surveillance system are essential in verifying potential inequalities and to succeed in the polio eradication initiative.A combination of high infant immunization coverage and surveillance of acute flaccid paralysis (AFP) cases, plays a critical role in polio eradication. This study aimed to estimate the incidence of AFP, to evaluate the completeness of AFP ascertainment during the years, age groups and gender, and to define the main associated diagnosis among children aged under 15 in the Marches region of Italy. Analysis was performed on data from the active AFP surveillance system and the hospital discharge records in the 2006–2014 period. The two-source capture-recapture method was applied. After cross-validation, 30 AFP compatible conditions as defined by the WHO were identified, with an incidence estimate of 1.91 cases of AFP per 100,000 children under 15 years . Guillain–Barrè syndrome was the most common diagnosis. A significant difference ( In May 1988, the World Health Assembly launched the Global Polio Eradication Initiative (GPEI) aimed to achieve the goal of global eradication of poliomyelitis by 2000. The goal was defined as no cases of clinical poliomyelitis associated with wild poliovirus and no wild poliovirus found worldwide. The strategy subsequently adopted by the World Health Organization (WHO) relies on four key strategies: high infant immunization coverage, mass campaigns, active surveillance for wild poliovirus and target “mop up” campaigns [Europe has been declared polio free since 2002. In Italy the last case of poliomyelitis due to transmission of indigenous wild poliovirus occurred in 1982 . In 2018Active surveillance for acute flaccid paralysis (AFP) is considered a very sensitive system to rapidly detect, report and investigate confirmed poliomyelitis cases. In countries in polio-free regions, AFP surveillance should be evaluated through indicators, such as by sensitivity of surveillance and completeness of case investigation . Indeed,The incidence in any population of AFP cases due to conditions other than polio (the non-polio AFP rate) is estimated to be one case per 100,000 children aged under 15 years . A countThe aims of this study were to estimate the incidence of AFP, to evaluate the completeness of AFP ascertainment by year, age groups and gender, and to define the main associated diagnosis among children aged under 15 in the Marches Region of Italy.In Italy, the surveillance of AFP was extended to a national level in 1997 and carried out by the National Institute of Health (ISS) and the Ministry of Health (MOH) through 20 Regional Reference Centres (RRCs). An AFP case is defined as a child aged under 15 showing clinical acute onset of flaccid paralysis in one or more limbs, or acute onset of bulbar paralysis .Clinical samples (consisting of two stool specimens and one sample of serum) are sought for each case and sent to the ISS for virologic investigations. After case notification, a follow-up questionnaire is required to be sent to the ISS and MOH to determine whether residual paralysis or death occurred 60–90 days after diagnosis, as well as to clarify the conclusive diagnoses. Virologic investigations are usually performed by ISS .The Chair of Hygiene at the Polytechnic University of the Marche is the RRC for the same region. The Marches are one of the twenty regions of Italy. The name of the region derives from the plural name of marca, originally referring to the medieval March of Ancona and to the nearby marches of Camerino and Fermo, representing its cross-border nature. The region is located in the Central area of the country on the Adriatic Sea, and has about 1.5 million inhabitants. On a two-weeks basis designated staff contacts by phone the reference doctors of 25 Operative Units  belonging to the network. For every AFP case the management is activated according to the directives of the ISS and MOH. The study was carried out retrospectively with data from 2006 to 2014. The primary data source was the regional database of AFP cases originating from notifications by phone to the RRC of Marche. The secondary data source comprised hospital discharge records (HDRs) including a diagnosis consistent with AFP-compatible conditions as defined by the WHO. Characteristics of paralytic polio are fever at onset, asymmetric flaccid paralysis, rapid progression of paralysis, residual paralysis after 60 days and preservation of sensory nerve function. The most common differential diagnoses of AFP include Guillain-Barré syndrome, paralytic poliomyelitis, and transverse myelitis [The authorization from the local Ethics Committee was not required, as the program belongs to a national ministerial project considering the WHO directives for the achievement of the poliomyelitis eradication (WHA 41.28 of May 1988). Research carried out on humans was performed in compliance with the Helsinki Declaration.The two-source capture-recapture method was used to assess the incidence of AFP cases, the sensitivity of the surveillance system to detect all AFP cases and the completeness of case investigation ,16,17,18N is the total number of cases, a is the total number of cases determined from the primary source , b is the total number of cases ascertained from the secondary source  and c is the number of cases established by both sources. In the present study, the number of AFP estimated cases has been calculated using the Chapman modification to the Lincoln–Petersen estimator for the capture-recapture method, as follows (2):In this study we compared cases from two sources to estimate the total number of cases, based on Formula (1):N is the total number of estimated cases. The difference between ascertained/estimated number of events has been assessed by the chi-squared test. The 95% CI for the population size was calculated using the ciChapman function from the recapr package, with the default bootstrap method. Analyses were performed with the r software. [Estimated completeness was calculated based on Formula (3):oftware.  The leveThe regional database of AFP cases notified to the RRC included information about six AFP cases in the 2010–2014 period, equivalent to an annual incidence of 0.54 per 100,000 children aged under 15 years . According to the recommended WHO target level, a minimum of 11 cases should have been recorded in the target population. Patients discharged with AFP-compatible diagnoses identified from the hospital discharge records led to 30 cases of hospitalization with an incidence estimate of 2.72/100,000 . The estimated completeness of ascertainment by the ongoing surveillance system was therefore 14.15%  was calculated in the estimated probability of case ascertainment in females; in fact, only 3.7% (N = 1) of estimated cases have been ascertained in the surveillance system versus 23.8% (N = 5) of cases in males.The average annual incidence of AFP, based on the capture-recapture method , was estN = 21) had the 357.0 ICD-9-CM diagnosis code, which is used for “acute infective polyneuritis”, such as Guillain-Barré syndrome, 16.7% of patients (N = 5) had the 344.89 code, that is applied for “other specified paralytic syndrome” , while 13% of them (N = 4) had the 341.22 code for “acute (transverse) myelitis NOS”.Considering all cases with a hospital admission, 70% , no case of AFP was notified by the phone surveillance. These results highlight the lack of exhaustiveness of the notification system in identifying AFP in children under 15 years and highlight the need for a change in the process.Vaccine-preventable diseases continue to pose a great risk to the community and the hospital setting. ,30 KnowlMoreover, enhancing the surveillance system will be a key to achieve a prompt identification of viruses potentially causing serious disease in the community.Surveillance has been supported by the Italian National Institute of Health.


During the deformation process of Wm in the SPT, for thermal aging for 10,000 h, some completely curved slip bands were generated inside the ferrite phase, which had no contact with the δ/γ phase interface and belonged to the slip bands produced by the independent deformation of ferrite. The combined effect of the curved slip bands and stress concentration led to the initiation of obvious micro-cracks at the δ/γ phase interface. The micro-cracks propagated along the ferrite phase curved slip bands, and eventually penetrated the entire hardened ferrite phase.The microstructural evolution and mechanical behavior of cast duplex stainless steels (CDSSs) at 400 °C for different thermal aging times were investigated by transmission electron microscope (TEM) and small punch test (SPT). The results showed that the spinodal decomposition in ferrite was the main reason for the decrease in toughness, and G-phase did not play an important role in the embrittlement process. The change of membrane stretching zone (W Cast duplex stainless steel (CDSS) is widely used in the primary coolant pipe of a pressurized water reactor (PWR) nuclear power plant because of its excellent comprehensive properties ,2,3,4,5.It has been reported that the increase of brittleness in CDSS during thermal aging is mainly due to the generation of the Fe-rich α phase and the Cr-rich α’ phase, and the precipitation of the G-phase for long-term thermal aging ,13,14,15For the CDSS after thermal aging, due to the spinodal decomposition in the ferrite phase and the generation of the G-phase, it is difficult for the hardened ferrite to deform and slip during the deformation process, which reduces the deformation coordination between the austenite and ferrite phases, resulting in the stress concentration at the interface of the austenite and hardened ferrite phases, which ultimately leads to the increase in brittleness and the decrease in mechanical properties. Therefore, it is particularly important to study the mechanical behavior of each phase after thermal aging. At present, many studies have been used to characterize the brittleness and deformation behavior of thermal aging through traditional tensile and impact tests ,20. The This study focuses on the microstructural characteristics of CDSS at 400 °C under different thermal aging times, and systematically observes the spinodal decomposition and second phase precipitation behavior in ferrite, revealing and summarizing the evolution of CDSS microstructure before and after the thermal aging process. It then analyzes and discusses the changes in microhardness properties. Moreover, the deformation behavior and fracture mechanism of CDSS before and after thermal aging are characterized and analyzed by means of small punch test (SPT). 1t and 2t are the service times at the temperatures 1T and 2T, respectively, Q is the Arrhenius activation energy, and R is the gas constant.The materials investigated in this study were CDSS Z3CN20-09M, which was obtained from a new component of the primary circuit piping. The chemical composition (wt.%) of the Z3CN20-09M material used in this study was as follows: 20.16 Cr, 8.93 Ni, 0.02 C, 1.07 Si, 1.02 Mn, 0.063 Cu, 0.026 Co, 0.22 Mo, Balance Fe. The test materials were then subjected to a thermal aging treatment at 400 °C, and the thermal aging times were 400, 1000, 5000 and 10,000 h, respectively. According to the Arrhenius equation as shown in Equation (1), the aging effect at 400 °C for 10,000 h was equivalent to 36.4 years at the service temperature  [SPT was a semi non-destructive test method. It had been widely considered as an effective test method to obtain the performance data of related materials by using small specimen sizes. The hardness of the ferrite and austenite phases was studied using a Vickers hardness tester under a load of 10 g. Large grain sizes were selected as much as possible, and the indentation should be close to the grain center, so as to avoid the influence of adjacent grains on the measurement results. Eight measurements were made for each test and the hardness value was the average of the eight measurements.In order to clearly show the phase interface, the metallographic sample was polished and then electrolytic etched with 10% oxalic acid. The microstructure characteristics under different aging times were observed by optical microscope . The ferrite contents in the OM images were quantitatively measured with ImageJ software . The error bars corresponding to the standard deviation were obtained by using the standard deviation function of the origin software. The microstructures before and after thermal aging were analyzed by a high-resolution transmission electron microscope  operated at 200 KV. After the load-displacements of the SPT were terminated, the deformation and fracture surface morphology of the specimens were observed by scanning electron microscope .In order to further study the effect of thermal aging on the ferrite phase of stainless steel, the ferrite phases in the microstructure are observed by TEM and HRTEM. F/ /{001}G{100}F/ /{110}G{110}F/ /{111}G{111}The microhardness values of the ferrite and austenite phases under different thermal aging times are shown in e), in which the elastic deformation occurs; (2) the plastic bending deformation zone (Wp), in which the plastic deformation occurs; (3) the membrane stretching zone (Wm), in which the material further plastic deformation occurs and the material undergoes obvious elongation; (4) the instability fracture zone (Wf), in which cracks appear in the small punch specimen, and the material has failed. We can see the load-displacement curves of the four zones with significantly different curvatures. In addition, the Wp and Wf are the main components of the load-displacement curve in the SPT. Therefore, the changes in the Wp and Wm of the small punch specimen, especially the Wm, dominate the changes in the mechanical properties of the material.e, Wp and Wf change little with the thermal aging time, but the energy of Wm changes obviously, which shows that the deformation behavior of the Wm is the main reason for the brittleness of the CDSS.It is believed that the area enclosed by the load-displacement curve and the horizontal and vertical coordinates can be defined as the small punch energy, so the small punch energy results of the specimens under different thermal aging times are shown in m plays an important role in the mechanical properties of stainless steel before and after thermal aging. Therefore, the differences in the deformation and fracture behavior in the Wm of the specimens with different thermal aging times are analyzed. m and Wf) after thermal aging for 0 h and 10,000 h. It can be seen that the specimen surface mainly includes two zones of Wp and Wm. In addition, the surface of the unaged specimen is still in a good plastic deformation state The thermal aging time of ferrite in CDSS began to precipitate the G-phase between 1000 and 5000 h, and the growth of G-phase in ferrite was promoted with the increase in aging time;(2)m in the SPT, the unaged ferrite phase could generate continuous linear slip bands throughout the entire ferrite. However, for thermal aging for 10,000 h, some completely curved slip bands were generated inside the ferrite phase, which had no contact with the δ/γ phase interface and belonged to the slip bands produced by the independent deformation of ferrite;During the deformation process of W(3)The combined effect of the curved slip bands and stress concentration led to the initiation of obvious micro-cracks at the δ/γ phase interface. The micro-cracks propagated along the ferrite phase curved slip bands and eventually penetrated the entire hardened ferrite phase.The microstructural evolution and microhardness properties of CDSS during thermal aging at 400 °C were investigated. Moreover, the deformation behavior and fracture mechanism of CDSS before and after thermal aging were characterized and analyzed by means of SPT. The major results can be drawn as follows: