Friction stir welding of 1016 pure aluminum and T2 pure copper with 2 mm thickness was carried out in the form of lap welding of copper on the upper side and aluminum on the lower side. The growth of interface microstructure between 1016 pure aluminum and T2 pure copper welded by friction stir welding was studied. The growth mechanism of the intermetallic compound (IMC) layer in the Cu-Al lap joint was revealed by annealing at 300, 350, 400 °C. The intermetallic compound (IMC) layer in the lap joint grows again during annealing, and only the original structure of the intermetallic compound (IMC) layer grows at lower annealing temperature and holding time. At higher annealing temperature and holding time, the original structure of intermetallic compound (IMC) layer no longer grows, and a new layered structure appears in the middle of the original structure. There is a gradient change of microhardness in the nugget zone. With different holding times, different softening phenomena appear in the metals on both sides of copper and aluminum. When the hardness decreases to a certain extent, it will not continue to decrease with the increase of holding time. When the annealing temperature is 350 °C and 400 °C, the strength of the tensile sample increases first and then decreases with the increase of holding time. At the interface of Cu-Al, the fracture runs through the whole intermetallic compound (IMC) layer. Two metastable phases—Al3Cu2 compound and non-equilibrium Al solid solution containing 13 at.% Cu—were found at the interface and on the Al side, respectively. According to the strain state in the welding process, an ideal shear texture is formed on both sides of the joint. Due to the formation of a large number of intermetallic compounds, the mechanical resistance of the joint needs to be improved. Sachindra Shankar et al. [4Cu9 and Al2Cu intermetallic compounds (IMCs) with a thickness of 2.2–0.26 μm was formed at different welding speeds. Intermetallic compounds (IMCs) with large volumes had an adverse effect on the tensile properties of the joint. When the welding speed was 160 mm/min and 213 mm/min, and the tool offset was 1 mm, the intermetallic compounds (IMCs) (0.26–0.77 μm) had little effect on the tensile properties. Lee et al. [Aluminum and copper are widely used in aerospace, electronics, chemical and other fields because of their excellent electrical and thermal conductivity ,2,3,4. Ir et al.  studied e et al.  annealedThe experimental material used 1016 pure aluminum  and T2 pure copper  in rolling state. The size of the plate was 200 mm × 100 mm × 2 mm. Its chemical composition is shown in In the figure, it can be observed that there are no macroscopic defects such as tunnels inside the weld, and a hook structure is formed at the edge of the stirring zone at the interface between the aluminum and copper. This structure is one of the typical characteristic structures of friction stir welding lap joints of dissimilar metals . When an2. As shown in 2 and copper. In A large number of crystalline structures can be observed under the copper–aluminum interface in The annealing holding time is fixed at 4.5 h, and lap joints with annealing temperatures of 300 °C, 350 °C and 400 °C are selected to observe the morphology of the microstructure in the “liquid phase zone” of the joints. The evolution process of the structure in this area during annealing is studied in comparison with the joints without annealing heat treatment. By comparing and observing the structural characteristics of crystals in different “liquid regions”, it is found that the structural changes in this region are mainly manifested in two aspects: on the one hand, the structure adjacent to the “liquid region” in the intermetallic compound (IMC) layer at the Cu-Al joining interface grows to the “liquid region”, and evolves from the original columnar crystal structure into a layered structure. On the other hand, there are dendrites in the “liquid phase zone” structure of the unannealed joint. With the progress of annealing, the original dendritic structure gradually disappears, leaving a dense particle structure. Comparing the growth environment of the tissue in the welding process with that in the annealing process, it can be seen that there is an obvious difference between them. Excessive heat input during welding leads to the appearance of a “liquid zone” inside the joint, and the growth direction and growth mode of the microstructure in liquid environments have a certain selectivity. It can also be seen in 2Cu, AlCu and Al4Cu9.4Cu9 + AlCu, becoming Al2Cu and an aluminum-based copper solid solution, and the intermetallic compounds (IMCs) formed in the intermediate structure of intermetallic compounds (IMCs) group into AlCu + Al2Cu, and are affected by the proportion of copper and aluminum in this range. From the above observation results, it can be seen that different intervals of intermetallic compounds (IMCs) are composed of different kinds of intermetallic compounds (IMCs), and the types of intermetallic compounds (IMCs) found in the corresponding interval are affected by the proportion of copper and aluminum elements in this interval. In the process of Cu-Al dissimilar metal friction stir welding, copper and aluminum combine under the action of friction heat and the stirring head, and intermetallic compounds (IMCs) are formed at the joining interface due to the mutual diffusion taking place between copper and aluminum atoms. In the process of diffusion, copper atoms enter into the aluminum matrix, and the corresponding aluminum atoms also enter into the copper matrix. Due to the limited diffusion of elements, the proportion of dissimilar metal elements diffusing into each other is relatively low. In this case, two structural forms will be formed, that is, the two-layer metal intermetallic compound (IMC) layer observed in this paper. The effect of the temperature field during annealing will once again promote the diffusion of copper and aluminum atoms, and with increasing number and depth of copper and aluminum atoms, the intermetallic compound (IMC) layer will grow and the thickness of the original structure will increase. With increasing annealing temperature and holding time, the atomic activity will increase, and the difference in the atomic ratio of copper to aluminum in the central region will decrease during diffusion. According to the binary phase diagram of Cu-Al, the type of intermetallic compounds (IMCs) formed under the ratio of copper to aluminum is different from the original intermetallic compound (IMCs) structure, so a new layered structure is formed in this region, which changes the original structure of the intermetallic compound (IMC) layer from a two-layer structure into a three-layer structure. Limited by the types of intermetallic compounds (IMCs) generated by Cu-Al, it would be difficult to form a new intermetallic compound (IMC) layer structure with a further increase in annealing temperature, but the thickness of the original intermetallic layer would increase accordingly.The microstructure of the intermetallic compound (IMC) layer in the joint was observed with a holding time of 1.5 h and an annealing temperature of 300 °C, 350 °C, and 400 °C. The EDS measurements of different structures in the intermetallic compound (IMC) layer show that, as shown in As shown in The tensile specimen of the lap joint after annealing treatment is shown in To understand the effect of the growth of the intermetallic compound (IMC) layer on the fracture behavior of the joint, the fracture surface of the tensile test was further analyzed. The fracture samples along the thermo-mechanical affected zone of the aluminum plate and the fracture samples along the Cu-Al interface were selected to analyze the fracture morphology. (1)The microstructure characteristics of Cu-Al lap joints after annealing were studied. Annealing treatment can promote the re-growth of intermetallic compounds (IMCs) in the joint. When the annealing temperature is lower and the holding time is short, only the thickness of the intermetallic compound (IMC) layer increases. When the annealing temperature and holding time are increased, the thickness of the intermetallic compound (IMC) layer increases and a new layered structure appears in the middle of the original intermetallic compound (IMC) layer.(2)The effect of the intermetallic compound (IMC) layer on the properties of lap joints was studied. Within a certain range, the performance of the joint can be improved by increasing the holding time of the annealing process and increasing the thickness of the intermetallic compound (IMC) layer.(3)By analyzing the proportion of copper and aluminum elements in different layered structures in intermetallic compounds (IMCs), the intermetallic compound (IMC) composition of different layered structures was determined.(4)The growth process of intermetallic compounds (IMCs) and the reason for the formation of new structures during annealing were revealed. The annealing process is able to increase the activity of atoms and promote the diffusion of atoms. In the process of diffusion, the proportion of copper and aluminum atoms in some regions is different from the initial state. A new layered structure is finally formed under the action of suitable temperature.The effect of post-weld heat treatment on the interfacial structure of Cu-Al and the relationship between mechanical properties were studied. Based on the present analysis, the following conclusions can be drawn:


This work deals with anomalous concentrations of natural mordenite in the southeast of Spain. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) studies evidenced that the samples contain mainly monomineral zeolitic phase of mordenite (70% to 74%), usually accompanied by smectite (montmorillonite), the principal component of bentonite. A study of the applicability of these zeolites is presented to establish the potential use as pozzolanic cements. For comparative purposes, synthetic commercial mordenite is also characterized and tested. The initial mixtures were prepared using cement and mordenite at a 75:25 ratio. Chemical analysis and a pozzolanicity test showed the high pozzolanic character. These mixtures were further added to sand and water, yielding the cement specimens to be used as concrete. Mechanical test results showed that the mechanical compression at 7 and 28 days fall into the range of 19.23 to 43.05 MegaPascals (MPa) for the cement specimens built with natural mordenites. The obtained results fall in the same range of cement specimens prepared with natural clinoptilolite, using mixtures within the European requirement for commercial concretes. Thus, these results and the low cost of natural mordenite of San José de los Escullos deposit supports the potential use of natural mordenite as pozzolanic cement. The manufacturing of one ton of cement produces about one ton of CO2, with the construction industry being responsible for about 7% of all CO2 generated in the world. In addition, a large volume of raw materials is required to produce the billion tons of concrete required worldwide each year. The use of supplementary cementitious materials (SCMs) in the fabrication of concrete has proven to be a sustainable way to overcame economic, environmental, and technical disadvantages, while attaining reliable mechanical or durability properties. One way to reduce these emissions is to decrease the amount of clinker present in the cement by replacing part of it with pozzolanic materials with cementing characteristics such as natural zeolites. Zeolites can react easily with bases favoring the formation of silicates and aluminosilicates which are able to harden upon hydration. In cement chemistry, CSH and CAH represent hydrated calcium silicates and hydrated calcium aluminates that can be easily produced upon the reaction of zeolites with Ca(OH)2 yielding an amorphous aluminosilicate compounds called pozzolana.Cement is the major constituent material used in the production of concrete. The main component of Portland cements is clinker, a mixture of calcium silicates and aluminates obtained after sintering calcium carbonate at 1400–1500 °C, in a process that produces COScientific knowledge and use of natural zeolites are fields in continuous expansion due to the appearance of new deposits or new applications. Mineralogical zeolitic varieties, such as heulandite and clinoptilolite, are commonly used in the manufacture of concretes, mortars , and in In this work, the intention is to contribute to bust mordenite  as a relevant component in these uses, together with heulandite and clinoptilolite. In particular, the mordenite we dealt with is found in a deposit in the southeast of Spain.Spain does not have large deposits of natural zeolites, despite its great geological variety and its geographical extension. Only a few previous studies published, mostly in Spanish, mentioned the presence of zeolites in outcrops of volcanic rocks of the Iberian Peninsula and in the Canary Islands. The study area is in Cabo de Gata, Almería, Spain, at 2°4′08″ west longitude and at 36°46′42″ north latitude. The dimensions of the deposit fluctuate between 350 × 200 m. There are two areas of exploitation: The first is in the north, while the second is in a south–southwest direction. The thickness of the mineralized zone is estimated at more than 50 m. The exploitation of the quarry began around 40 years ago and is commonly commercialized as bentonite.The application of natural zeolite in the manufacturing of pozzolanic cements has been known since the Roman Empire, however, the first scientific reports are from the early 20th century, and show a growing trend in the late 90s until recent decades . Clinopt2, produced by the manufacturing of cement (estimated 756 kg of CO2 per ton of clinker), was decreased by replacing part of the cement with zeolites, so that by using a mixture of natural zeolite and cement, “green concrete” is obtained, for which the manufacturing processes show a lower impact on global warming than those of ordinary Portland cement [However, the occurrence of mordenite deposits  awoke ind cement . 2 emissions could be reduced by 23% (approximately 4 Mt/year). In this direction, our aim is to obtain concrete based on natural mordenite (MOR) from Spain, using ratios according to the European regulations UNE-EN 196-1:2011. By replacing 25% of the 22.8 Mt of cement feasible for commercialization in Spain in 2020,  the CO2 The natural mordenite samples to be studied were taken from different points of the San José-Los Escullos deposit. The four natural samples were collected through manual sampling of lithic fragments of outcrops. Samples labeled Z-9 and Z-12 were collected in the north area of the San José-Los Escullos deposit, where the presence of zeolitic rocks was clearly identified given the sharp interaction with the host rocks. On the other hand, samples Z-7 and Z-26 were obtained in the central part of the deposit as indicated in The identification of the phases is carried out by X-ray diffraction , and theThe analysis of the X-ray diffraction showed very similar profiles among the natural mordenite samples, composed mainly of MOR structure , with impurities of smectite  calculations are included in The surface area of the richest MOR sample was measured. The obtained result for sample Z-7 is rather high compared to other natural zeolites  yet muchAs it can be observed, the sample purity decreases from Z-7 to Z-26, with Z-7, Z-9 and Z-12 above 70%, which is a considerably high value for a natural zeolite deposit. This tendency could be explained based on the location within the deposit because the concentration of mordenite in the deposit decreases as the hydrothermal solutions approach the host rocks, which consist of pyroxenic andesites, dacites, and dacite tuffs. Thus, there is a marked zoning in the mineralization, characterized by an anomalous concentration of monomineral mordenite in the central part that gradually decreases towards the flanks. With the decrease of the mordenite content, there is an increase of the smectites at the same time . AccordiThe morphological studies of the samples were conducted by scanning electron microscopy in order to survey the homogeneity of the identified natural mordenites from Spain. Sample Z-7 shows a relatively homogeneous dispersion of crystals in the range 10 to 20 µm, with the random presence of larger agglomerates with elongated dimensions of 50 to 100 µm. The presence of high atomic number phases could be observed as bright spots in Z-7, since the scanning electron microscopy (SEM) microscope employed used a backscattered detector. These bright spots, marked with white arrows in Further studies in the B-01 sample  allowed Finally, synthetic mordenite  is compoThermogravimetric studies were also carried out due to the relevance of the water content to the application in cements. Total weight loss has been included in The profiles in Above 350 °C, the differences between the samples are more evident, indicating the loss of water from the constitution of smectite. Condensation of silanol groups contributed to this event with a very slow mass loss due to the loss of water from the constitution and the decomposition of the sample. The loss of mass is less pronounced and can reach 1%, the structural stability limit of synthetic mordenite. Between 700 °C and 900 °C, there is a normalization of the curve, in which no loss of mass is determined, which corresponds to the structural rearrangement in post dehydration/dehydroxylation conditions with no compositional changes.The values represented in In order to evaluate the properties of these zeolites as pozzolana, mixtures of 75/25 cement/mordenite were prepared according to the European Standard . Table 32 reaches the highest value, 73%, which is 98.6% of the total SiO2 of the mixture. This means that virtually all the silica in the sample reacts with the cement while keeping the MgO, CaO, and Fe2O3 in low values, as indicated by the European Standard Regulations [2 but the decrease in the reactive SiO2 shows 10% to 15% decrease due to the impurities present in these samples that hinder the reactivity. Surprisingly, the sample with the highest content of reactive SiO2 is Z-26, with 63%, which represents 88% of the total silica, while these samples showed the least purity (67% in mordenite). On the other hand, Z-7, being the purest sample, shows the lowest reactive SiO2 . This explains the high percentage of insoluble residue observed. The XRD of the sample Z-7 allowed for identifying strong peaks of quartz, for which the crystalline structure is very strong, hindering the reactivity and therefore appearing as an insoluble residue. However, as we will see in the results of compressive strength, this factor does not negatively influence the final properties of the cements because it is a resistant and stable material which does not produce further reactions with other components of the cement leading to changes in its composition or properties.These results are indicative of the final reactivity of the cement, and therefore, the composition varies as a function of the active additives added to the mixture. Since the percentage of additive in the mixture is constant 25%), the variations will be directly related to the nature of the zeolite sample employed. The samples are rich in silica and alumina, as expected, given the zeolite composition. When the mixture contains 25% of synthetic mordenite (Sin-01), the reactive SiO%, the va2 and Mg(OH)2 which take up more space than the original oxides, therefore they can cause harmful expansions; consequently, all cement standards limit the contents of free CaO and MgO. The results obtained by the natural zeolite samples were below these limits, so it can be concluded that the cement made with these samples will not be damaged by the expansions produced by the presence of these oxides.Free CaO and free MgO react with water to form Ca(OH)2 contained in an aqueous solution, in contact with the hydrated cement, and the amount of Ca(OH)2 necessary to obtain an aqueous saturated solution with the same alkalinity as the previous one. The test is considered positive if the samples are positioned below the isothermal of solubility at 40 °C in the graph (plotted in 2 in solution is lower than the saturation concentration. The studied samples were tested according to the European Standard Regulation [The pozzolanic activity was determined by comparison between the amount of Ca(OH)gulation .In the pozzolanic activity test, all samples are below the isotherm of solubility at 40 °C, which involves a high pozzolanic character of the samples tested. The synthetic mordenite (Sin-01) has a behavior towards magnitude 0 of calcium oxide concentration (mmol/L), which indicates the ability of the zeolite to react quickly with the cement in solution. The natural zeolite samples have a strong similarity in pozzolanicity given their position in the graph, maintaining all of them a positive value.The Ultrasonic Pulse Velocity (UPV) method was used for ultrasound analysis, which provides the time it takes for a wave to travel a distance through the specimen. Knowing the time readings and the travel distance of the waves, the speed of the ultrasonic waves was calculated. In all samples, an increase in the speed of the ultrasonic waves is observed as the setting time increases. This behavior may be related to the removal of water that occurs as the setting of the specimen progresses, which favors the increase of the mineral phase . The purThe compressive strength was performed on the specimen half-prisms resulting from the bending strength to indicate the maximum stress a material can support under a crushing load until it breaks. This is calculated by dividing the maximum load by the original cross-sectional area of a specimen in a compression test, following the indications of the European Standard . Figure Initial and final setting times of the pastes were determined with the Vicat needle test according to the European Standard . For theThe results presented above, obtained for the characterization of the natural mordenite samples through X-ray diffraction and scanning electron microscopy, indicate a mineralogical composition consisting of the main phase of mordenite and a secondary phase consisting of smectite and quartz and small quantities of metallic minerals. Despite knowing the percentage of the phases identified as impurities present in the samples, it is known that the natural samples have a complex composition, mainly formed by mafic and felsic minerals, such as amphibol, pyroxene, biotite and feldspar, followed by minor amounts of quartz, opal-CT/cristobalite, and smectite among others , which m2/g, which was the same specific surface that the cement reference.The tested samples were composed of four natural samples taken from different points of the San José-Los Escullos deposit and one synthetic mordenite sample. The four natural samples were taken through manual sampling of lithic fragments of outcrops. Samples labeled Z-9 and Z-12 were collected in the north area of the San José-Los Escullos deposit, where the presence of zeolitic rocks was clearly identified given the sharp interaction with the host rocks. On the other hand, samples Z-7 and Z-26 were obtained in the central part of the deposit, as indicated in Synthetic mordenite was purchased from Zeolyst, code CBV10A, supplied in fine powder form which does not require further granulation particle treatment.In addition, a sample of natural bentonite labeled B01, was taken from the host rock for comparison purposes.X-ray diffraction was performed in a Philips diffractometer X′ PERT using the radiation CuKα (λ = 0.154 nm). The percentage of mordenite present in the samples was calculated by measuring the area of the main mordenite peaks concerning the total area of the diffractogram of each sample. Nitrogen adsorption–desorption isotherms were measured at −196 °C using the micrometrics ASAP 2420 and BET calculation. Scanning electron microscopy studies were performed on a Hitachi TM-1000 Tabletop equipped with EDX. In these cases, the samples were observed without coating. A higher resolution SEM was employed to image synthetic mordenite. A Philips XL30 S-FEG was employed using Cr coating of the sample (Quorum. model Q150T s). X-ray fluorescence was carried out using a Philips WDXRF spectrometer (PW 1404) equipped with a collimator to reduce the angle of divergence of the x-rays. A Perkin-Elmer TGA7 thermobalance was used for the thermogravimetric analyses in a range of 25 to 900 °C using a heating ramp of 20 °C/min in an atmosphere of air.The mixture used in the characterization of the pozzolanic cement was composed of 75% of a reference cement type II 42.5R and 25% of mordenite. The chemical analyses of the mixtures were carried out following the European Standard Regulations , which sTests carried out to determine the application of the study material as concrete was conducted on prismatic specimens of 40 × 40 × 160 mm composed of 400 g of mixture, with a 75/25 ratio of cement/zeolite, 225 g of standardized CEN sand, and 225 of filter water (water/cement ratio 0.50). The cement used was a reference cement type II 42.5R.The preparation of the cement specimens was carried out by the European Standard .The determination of the speed of ultrasound propagation was carried out following the European Standard  accordinA CONTROLS-UPV E48 ultrasound equipment was employed using Ultraschall-Gel Sauerland as a contact gel.The bending resistance test was carried out following the European Standard . The thrThe initial and final setting processes were tested under the specifications set out in the European Standard  with theThe results of the chemical analysis of the mixture made of 75/25 cement/zeolite ratio of the mordenite samples both natural and synthetic allow us to conclude that they are suitable for use as additives in the production of pozzolanic concrete because their values are within the limits established by the regulations. However, an exception is the value of the insoluble residue determined in the samples of natural mordenite due to the presence of non-reactive silica. This does not adversely affect the durability of the concrete. The determination of pozzolanicity indicates that the Spanish natural mordenites are materials with high pozzolanic reactivity. The tests carried out on the mixture of cement and mordenite have allowed us to determine the behavior of the samples in their final application, showing that despite containing impurities and the difficulties of characterizing natural samples, these are perfectly valid as active additives in cement.


This study aims to deeply understand the effect of contact stress and slip ratio on wear performances of bainitic rail steels. The results showed that the wear loss increased as the contact stress and slip ratio increased. Based on the surface damage morphology and microstructural analyses, it revealed that the rolling contact fatigue wear mechanism played a significant role under the low slip ratio, but the dominant wear mechanism transferred to the abrasive wear at the high slip ratio. Meanwhile, the bainitic steel specifically presented worse wear resistance under the abrasive wear mode. Compared with the influence of a slip ratio, the increase in contact stress led to severer plastic flows and contributed to the propagation of cracks. In addition, the contact stress and slip ratio had the opposite effect on the friction coefficient, that is, the friction coefficient of bainitic steels behaved the inverse proportion with the contact stress, but positive proportion with the slip ratio. At last, the increase in slip ratio had more significant effect on the reduction of retained austenite (RA) than the enlargement of contact stress due to the fact that the RA would probably be removed before the martensitic transformation occurred under the abrasive wear mechanism. Pearlitic steel has been widely used in railway system, but the conventional pearlitic steel is susceptible to the formation of various defects, such as head checks and corrugation under actual rail-wheel contact conditions, which may lead to rail fracture and consume a great deal of maintenance cost and time ,2,3. ComIn recent years, many field and laboratory studies have been carried out to investigate the wear performances and damage behaviors of pearlitic rail and wheel steels ,11,12,13As for the bainitic steel, several studies mainly focused on the comparison of the wear resistance ,17,18,19On the other hand, in some previous studies, bainitic steels often presented poor wear resistance ,23,24. SThere have been relatively few studies concerning the intrinsic wear performances of bainitic steels under different working conditions, except in these contrastive researches between bainitic and pearlitic steels. Specifically, in practical wheel-rail contact, the contact stress and slip ratio should be considered as important parameters affecting the durability and tractive stability of wheel and rail system. It is still unclear how these two parameters affect the properties of bainitic steels. Studying the defect types and wear mechanisms of bainitic steels under different contact stresses and slip ratios could contribute to evaluate and predict the wear behavior and service life of bainitic rails. The results could also benefit the proper application of bainitic rail steel in complicated railway fields.Within the complex microstructure of bainitic steel, retained austenite (RA) played an important role in the wear resistance ,28,29 anIn this study, the effect of contact parameters on the wear performance of carbide-free bainitic rail steel was studied by changing the contact stress and slip ratio, in order to deepen the understanding of wear mechanism of bainitic steel under different working conditions. The findings would contribute to a better field application of bainitic rails in future.In this experiment, MJP-30A RCF testing apparatus was used to conduct the dry rolling-sliding wear tests in order to evaluate the wear performance of bainitic rail steel. This test rig was assembled by Tribology Research Institute, State Key Laboratory of Traction Power, Southwest Jiaotong University. The rail and the wheel rollers were clamped on two rotating shafts driven by independent motors. The slip ratio can be adjusted by setting different rotating frequency of two motor shafts. The detail of sampling diagram can be found in the Ref. . The speThe bainitic rail steel (U22SiMn) and pearlitic wheel steel (CL60) were selected for wear tests. The bainitic rails were produced with the following procedures. The ingot of bainitic steel was heated to 1150 °C and held for 1 h. The initial hot rolling temperature began at 1150 °C, the finishing rolling temperature was not lower than 950 °C. At last, the air-cooled bainitic rail steel was reheated to 350 °C for two hours tempering. The temperature of 350 °C could not lead to the temper brittleness based on the previous experimental results. The chemical composition and mechanical properties are shown in 2 which was not close to the elliptical contact patch in the real wheel-rail contact which is about 110 mm2. The value of Young’s modulus selected in this calculation was 205 GPa, and the value of Poisson’s ratio was 0.3. The applied normal forces were designed to 4300 N, 2850 N and 500 N. According to the Formulas (1) and (2) [b: Contact half-width; F: Applied normal force; ν1, ν2: Sample-1(2) Poisson’s ratio; E1, E2: Sample-1(2) elastic modulus; d1, d2: Sample-1(2) diameter; l: Contact length of cylinders.In this experiment, Hertzian contact criterion  was adop and (2)  the contThe maximum contact stress is:An electronic analytical balance  with an accuracy of 0.0001 g was used to measure the weights of the rail roller and wheel roller before and after the experiment. Each sample was weighed three times and the average value obtained. The micro-hardness of the surface and cross-section of test specimens was measured by the Vickers hardness tester . A roughness meter  was used to record the surface roughness of the worn samples. Longitudinal cross-sections (with the arc length of about 8 mm) of the rail/wheel discs were cut off along the rolling direction for metallographic analysis. Each cross-sectional specimen was inlaid in the resin to protect the edge of the worn surface. Ground with SiC paper of 500 and 1000 grit, polished with 3.2 μm diamond, and etched with 4% Nital for 10 s, the microstructure of each section could be clearly analyzed with the optical microscopy  and scanning electron microscopy .α, (211)α, (200)γ, (220)γ and (311)γ diffraction peaks, the deviation value in retained austenite fraction is about 1.0%. The relevant method of estimation and equations can be seen in the paper written by Xu [The volume fraction of retained austenite was determined by X-ray diffractometry  which was equipped with Co-Kα radiation. The information of diffraction X-ray in the range of 30–115° was collected by the Lynxeye XE detector in scanning step of 0.02°. The calculations of the volume fraction of RA were based on the integrated intensity of (200)en by Xu .The mass loss of the wheel and rail samples for four testing sets was calculated and shown in f × R, where Tf represented the friction force and R was the radius of the specimen. At the end of the tests, the corresponding friction torque and roller radius for each test group would be recorded and measured. Finally, the friction force and the coefficient of friction at stable wear condition (50 k rolling cycles) can be obtained in The friction coefficient of the wheel-rail contact zone is an important factor affecting wheel-rail wear and traction in actual conditions. Therefore, in present work, the coefficients of friction under different contact stresses and slip ratios were specifically investigated. The real-time friction torque could be recorded by the MJP-30A RCF testing apparatus as shown in The surface roughness may affect the coefficient of friction between the discs and the distribution of stresses near the surface during test . Pin-on-After running 50,000 cycles, the post surface hardness was measured with the micro-hardness tester by averaging five points on the worn surface   for bainIn order to investigate the influence of contact stress and slip ratio on the surface damage of bainitic steels, scanning electron microscopic analyses were conducted  indicated that there was strong surface fatigue wear with severe plastic deformation. The formation of furrow morphology was due to the cutting of materials by the hard particles which slid between the contact surfaces. It can be seen from the For studying the development of cracks, cross-sectional microstructures of bainitic steels were analyzed. The number of cracks, crack depth, and inclination angle were measured from the SEM images , cracks were almost invisible in the bainitic rail surface, but there were some evident cracks on the worn surface in the cases of 1430 MPa (1#) and 1150 MPa (2#) shown in . MoreoveSpecimen in 1# test had the largest deformed layer with a thickness of about 268 μm, and the smallest plastic area with the depth of about 64 μm was observed in the subsurface layer of 3# specimen. Notably, with the same slip ratio, the depth of plastic deformation layer of bainitic rail steel increased with the increase of contact stress. However, in tests of 3# and 4#, the thickness of the plastic deformation layer was nearly similar. It revealed that the influence of slip ratio on the depth of plastic deformation layer was less than the contact stress. Meanwhile, according to In the present test, X-ray diffraction experiments were performed on the contact surfaces before and after the test, as shown in Comparing three sets of experiments at 2% slip ratio, i.e., 1#, 2# and 3#, it can be seen that the wear loss nearly linearly increased with the contact stress as shown in Comparison with the wear behaviors of pearlite rail steels in paper , the aut0)/shear yield strength (k)). When the parameter of p0/k exceeds the prescribed shakedown limit of studied bainitic steel, there will be a larger possibility to form severe plastic flows and make the growth of cracks. The shear yield strength (k) could be calculated by the formula [0/k for these three sets of tests with the contact stress of 1430 MPa, 1150 MPa and 500 MPa can be calculated as 1.05, 0.85 and 0.42, respectively. Therefore, the larger contact stress has much more tendency to develop plastic flows and contribute to the propagation of cracks in the surface layer.As shown in  formula  as folloWith the same condition of applied contact stress (500 MPa), compared to wear tests of 3# and 4#, it can be seen that the wear loss of bainitic steel at 10% slip ratio was almost nine times of the wear loss at 2% slip ratio (as shown in The reasons for the above results can be explained by two common wear mechanisms. Based on the surface observation in Schematically shown in In addition, from the analysis of surface roughness in the By comparing the crack features between 3# and 4# in the Based on the XRD spectrums in The effect of RA on the wear resistance of bainitic steel has been extensively studied. Some scholars believed that the RA on the worn surface underwent martensitic transformation, which resulted in a dramatic increase in hardness, compared with materials containing no RA ,25,42. MTherefore, it is reasonable to presume that the evolution of RA in the 4# specimen during the rolling/sliding test may not go through the MT. There is an interesting idea proposing that the stability of RA has a greater influence on the wear resistance than the amount of retained austenite ,28. On tIn summary, the bainitic steel showed the better wear resistance at the low slip ratio due to its excellent toughness acting on the RCF wear mechanism. However, the bainitic steel is not suitable for the small-radius curves with high slip ratio due to its worse wear resistance under the abrasive wear mechanism.The wear loss increases with the rise of the contact stress and slip ratio, but the slip ratio plays a more crucial role on aggravating wear loss than the contact stress.The rolling contact fatigue wear mechanism plays a significant role under the low slip ratio condition, but the dominant wear mechanism transfers to the abrasive wear at the high slip ratio. The bainitic steel is not suitable for the small-radius curves with the high slip ratio due to its worse wear resistance under the abrasive wear mode.The enhancement of contact stress has much more tendency to develop plastic flows and contribute to the propagation of cracks in the bainitic steels than the increase in slip ratio.The friction coefficient of bainitic steels has an inverse proportion with the contact stress, but positive proportion with the slip ratio.The volume fraction of RA decreases with the increase in contact stress and slip ratio. The increase in slip ratio has a more significant effect on the reduction of RA than the enlargement of contact stress due to the fact that the RA phase would probably be removed before the MT occurred under the abrasive wear mechanism.


Considering the importance of the role and function of pre-hospital emergency and community health and the need for continuous monitoring of traffic accidents and the process of service to patients, the present study was conducted to investigate the pre-hospital emergency services of the cities of Isfahan during one year in traffic accidentsThis study was a descriptive-cross-sectional study. The statistical population consisted of all traumatic victims injured in the emergency operation area of 115 provinces of Isfahan from April 1, 1997 to the end of February. The files were 61994 cases. Data were recorded by the Esfahan Emergency Department s Mission Information Registration Form E-patients were extracted and analyzed using SPSS18 software.Of the total number of missions in 22 provinces of Isfahan province, 44.2% belonged to Isfahan and then Najafabad city was 4.8%, and the cities of Khomeini were 7.7% and Lenjan, 7% of the missions. 78% of the missions resulted in admission, 11% outpatient, 10% abandonment of the mission and 1% infidelity, which was examined separately and comparatively.Improving the training and skills of pre-hospital emergency staff and culture-building, and changing the society s attitude toward receiving its services is the key to improving the status quo.Pre-hospital Emergency, Traffic Accidents, Isfahan Province


This article presents the application of a computational fluid dynamics (CFD) finite volume method (FVM) model for a thermo-mechanical coupling simulation of the weld pool used in variable polarity plasma arc welding (VPPAW). Based on the mechanism of the additional pressure produced through self-magnetic arc compression and the jet generated from mechanical plasma arc compression, and considering the influence of arc height and keyhole secondary compression on arc pressure, a three-dimensional transient model of variable polarity plasma arc (VPPA) arc pressure was established. The material flow behaviors of the perforated weld pools were studied. The results show that three kinds of flow behavior existed in the perforation weld pools and it is feasible to predict the weld pool stability by the material flow behaviors of the perforated weld pools. The weld pools can exist stably if the material flow in the bottom of the perforated weld pools can form confluences with moderate flow velocities of 0.45 m/s, 0.55 m/s and 0.60 m/s. The weld pools were cut when the material flowed downward and outward with the maximum velocity of 0.70 m/s, 0.80 m/s. When the maximum material flow velocity was 0.40 m/s, the weld pool collapsed downward under the action of larger gravity. The thermo-mechanical coupling model was verified by the comparison of the simulation and experimental results. Aluminum alloy 2219 (AA2219) has the characteristics of high specific strength, good mechanical properties at low and high temperatures, high fracture toughness and excellent stress corrosion resistance. It is one of the ideal materials for manufacturing large-scale space tanks ,4,5. HowHan et al. ,7 investTherefore, numerical simulation analysis regarding to the material flow behavior of AA2219 weld pool has seldom been carried out. However, AA2219 has a high thermal conductivity, so it dissipates heat quickly in the welding process, and the keyhole of AA2219 is more hardly formed than that of steel or 5-Series aluminum alloy in VPPAW . TherefoVPPAW essentially belongs to perforated welding, and thus, the keyhole evolution is extremely important. Generally, the keyhole is formed in several seconds, which is proposed to be the dominant driving force of arc pressure . The arcIn our study, an improved three-dimensional transient arc pressure model affected by multiple parameters was developed based on the principle of additional pressure produced through self-magnetic arc compression and the jet generated by plasma arc compression. In addition, the model considered the influence of arc height and keyhole secondary compression on the arc pressure, which firstly decreased linearly with the increase in the arc height and increased squarely with the increase in the keyhole depth after the keyhole formation. The influence of the perforated weld pool flow behaviors on the weld pool stability was investigated. The simulation results were verified by experiments. The weld pool stability, predicted by the material flow behavior of the perforated weld pool, is feasible and the application of the computational fluid dynamics (CFD) finite volume method (FVM) model for a material flow behavior simulation for VPPAW is practical in formulating and improving the welding technology during production.The VPPA welding and data acquisition system was schematically shown in The workpiece employed in this study was an AA2219 plate with a chemical composition as shown in The dimensions of the workpiece was 120 mm × 60 mm × 6 mm (length × width × thickness). The shielding gas used was pure argon with a volume fraction of 99.99% throughout the experiments. The high-speed camera technology was used to capture a real-time evolution image of the back keyhole.The welding parameters are summarized in ion film .The model was developed in an Ansys–Fluent environment based on FVM, which allowed the simulation of the VPPA welding process to be conducted.(1) Molten metal is considered as a laminar incompressible Newtonian fluid affected by the plasma arc pressure, surface tension, electromagnetic force and gravity .(2) A Boussinesq approximation was used to treat the buoyancy term .(3) The thermal conductivity, specific heat, surface tension and viscosity are related to temperature, whereas the other thermo-physical parameters are constant .The continuous equation, momentum conservation equation, and energy conservation equation need to be solved to obtain the perforation process and the weld pool flow behavior for VPPAW.t is the time, The continuous equation can be expressed through Equation (1):x, y, z directions can be written as follows:u, v, and w are the velocities in x, y, and z directions, respectively; x, y and z direction, respectively; The momentum conservation equation in the The momentum loss in the solid–liquid two-phase region is described as follows:In the solidification process of the weld pool, the amount of flowing liquid metal gradually decreases to zero, which leads to the momentum loss of the flowing metal. An enthalpy–porosity technique is used to deal with the momentum loss of a solid–liquid zone  ρ[∂HThe welding current in VPPAW, which changes in stages, has a significant impact on energy input into the weld, and thus the current expression should first be determined. As shown in tan α = (Stt0); tan β =t0 is the preheating time; The current variation in The heat transfer model ce below .x, y, z) points is expressed as follows:m1 is the distribution coefficient of the double ellipsoid heat source, The heat flux distribution of the double ellipsoid heat source at the  points is expressed as follows :(19)qv=qP is the total arc pressure, The arc pressure is an important factor in the keyhole evolution. Based on the mechanism of additional pressure produced through arc self-magnetic compression and a jet generated by plasma arc mechanical compression, a three-dimensional transient arc pressure model was developed. In addition, considering that the arc pressure first decreases with the increase in the arc height, and then increases with the additional constraints of the keyhole after the keyhole formation, the arc pressure model is further optimized. The plasma arc pressure can be expressed as follows :(20)P=P0The arc column expanding from the nozzle to the workpiece is assumed to have a conical shape, and the current distribution along the solid angle of the cone is uniform. A schematic diagram of the electromagnetic static arc pressure distribution is shown in I is the welding current calculated through Equation (17), z-axes and the axis of observation point A, and The static arc pressure at any position in the arc column (ion (21) (21)P0′=K’ is an adjusting coefficient which is introduced to consider the influence of the change in plasma gas flow rate on The static arc pressure at the center of the plasma arc is the largest when  concave  under thV is the velocity of the plasma jet, The distribution of energy and force at the interface between the keyhole and the weld pool is fatal for the keyhole formation and maintenance ,20. Duri5 N/m2. After igniting the plasma arc, the velocity in Section B is calculated through the following equation:18,000 K , and K″ Because the velocities in the arc axes decrease gradually along the downstream direction, owing to the additional pressure, the gradient decreases from the nozzle to the weld pool surface. Here, P can be obtained as follows: the arc pressure inside the workpiece conforms to a Gaussian distribution [d is the nozzle diameter; r is the radius of an arbitrary cross section; To summarize, in VPPAW, the total arc pressure ribution :(26)P=, width (y-axes) and height (z-axes) of the workpiece are 30 mm, 15 mm, and 10 mm, respectively. The domain is divided into three layers, the middle of which is a 6-mm fluid layer. The upper and lower layers are 2-mm air layers. The minimum grid size is 0.3 mm.The computational domain for the VPPAW model is shown in F = 1 corresponds to cells full of metal fluid, while F = 0 corresponds to cells empty of metal fluid. Cells with F lying between 0 and 1 locate in the free surface.A two-phase  flow model was used . In thisT is the real-time temperature of the weld pool.The surface tension of the gas-liquid interface is adopted using the continuum surface force (CSF) model  and calcSome thermo-physical properties of AA2219 were set out in For AA2219, the temperature dependence of density is represented by the following linear equation :(31)ρ(T)The specific heat capacity and viscosity of AA2219 are set through the following equations :(32)Cpk(T)T is the temperature of the weld pool. In Equation (34), In Equations (31)–(33), Firstly, the numerical results of case A were analyzed, including the dynamic change of the keyhole size, the arc pressure distribution on the keyhole surface, the temperature field and the flow behavior of the molten metal in the weld pool.The simulation results show that the maximum arc pressure during the DCEN and DCEP phase are 2600 Pa and 3000 Pa as shown in In order to verify the accuracy of the arc pressure model, an arc pressure measure and data acquisition system were set up schematically, as shown in The system consisted of a welding power source (VPPA-2), a plasma arc welding torch (PAW-300), a pressure transmitter (YB005-01) developed by General Engineering Research Institute of China Academy of Sciences, an Agilent memory oscilloscope (6422D) and an industrial computer data acquisition card (PCL1800) produced by Advantech. The welding power source was the self-developed VPPA-2 variable polarity plasma inverter with an 80C196KC single chip microcomputer as the control core and the main circuit as the double inverse circuit topological structure. The plasma arc pressure was transmitted to the pressure transmitter through the copper plate with the keyhole and the copper tube. The output voltage signal of the pressure transmitter was collected synchronously by the industrial computer and the memory oscilloscope.The signal converter converts the voltage signals into digital signals. The waveform measured by the oscilloscope corresponds to the arc pressure. As The calculated keyhole diameter is 1.86 mm, which is consistent with the measured value of 1.82 mm.The calculated fusion line (FL) is consistent with the measured fusion line obtained from the experiment, as shown in For case b–f, simulation tests and welding experiments were successively carried out with the welding parameters in For case a–f, the simulation results of the material flow of the perforated weld pool and phase distribution are shown in For cases a–f, the temperature gradient inside the weld pool was studied to further explore the mechanism of the weld pool material flow behavior to weld pool stability. The temperature value of the z = −5 mm straight line on the xoz plane was extracted. Since the weld pool is symmetrical, the temperature value within 3.5 mm (from the keyhole center to its right side) is shown in x-axis for cases a–f, the boundaries of the perforated weld pool were shifted to x = 6 mm in order to compare the slope of the temperature gradients. As shown in Due to the different horizontal distances from the weld pool boundary to the In In order to summarize the simulation results, according to the material flow behavior in the lower part of the weld pool, the equilibrium coefficient ƞ is introduced.When 1/4 ≤ ƞ < 1/3, such as in case a, case c and case e, the material flows to form confluences towards the keyhole center with the moderate velocities , and the weld pool can exist stably. When ƞ ≥ 1/3, such as in case b and case d, the material flows downwards and outwards with the maximum velocities of about 0.7 m/s or 0.8 m/s, and the weld pools are cut. When ƞ < 1/4, the maximum downward flow velocity of the perforated weld pool was 0.4 m/s and the weld pool with too large an amount of molten metal, caused by the long-time metal refluxing phenomenon, collapsed downward under the action of a larger gravity.The different weld formations further verify that it is feasible to predict the weld pool stability by the material flow behavior of the weld pool.(1) It is feasible to predict the weld pool stability by the material flow behavior of the weld pool. The weld pool can exist stably when the material in the bottom of the weld pool can form confluences with the maximum flow velocities of 0.45 m/s, 0.55 m/s and 0.60 m/s. The weld pools are cut when the material flows downward and outward with the maximum velocities of 0.7 m/s and 0.8 m/s, and metal gaps appear according to the law of mass conservation. When the maximum material flow velocity is 0.40 m/s, the metal refluxing phenomenon occurs in the weld pool for a long time, increasing the amount of the molten metal. The gravity of the weld pool increases with the amount of molten metal, so the weld pool collapses downward under the action of a larger gravity.(2) Based on the mechanism of the additional pressure produced through self-magnetic arc compression and the jet generated from mechanical plasma arc compression, and meanwhile considering that the arc pressure first decreases with the increase in arc height, and then increases with the additional constraints of the keyhole after the keyhole formation, a three-dimensional transient model of the VPPA arc pressure which first decreases linearly with the increase in arc height and then increases squarely with the increase in keyhole depth was established.(3) The measured arc pressure value, the shape of the fusion line, and the keyhole size on the back of the weld were in good agreement with the simulation results.


Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients. The 21st century was marked by a change in the paradigm of tumor perception. Scientists have established the important role of the immune system and inflammation in cancer development and especially the role of T cells. This concept was not only useful as an academic discovery but it also led to development of several novel treatments, as well as anti-immune checkpoint therapies  that were rewarded by the Nobel prize of 2018. Immune cells have the ability to infiltrate tumors and form with other untransformed cells the tumor microenvironment (TME) . The comIn this review, we will focus on the different functions of this very complex system and how they can influence patient’s outcome, depending of the cancer types or the pathway activated.The first description of the complement system in 1890 assigned it antimicrobial functions . However2O), a bio-active form of C3, structurally and functionally similar to C3b. C3(H2O) can bind Factor B (FB) that could be cleaved by Factor D (FD) into Bb and Ba fragments, forming the fluid phase alternative pathway C3 convertase: C3(H2O)Bb, cleaving C3 into the anaphylatoxin C3a and opsonin C3b. In absence of activation the newly formed C3b will be hydrolyzed. In presence of an activating surface, C3b will bind covalently, recruit FB and FD, thereby forming the alternative C3 convertase (C3bBb). This mechanism allows the establishment of an amplification loop to increase the C3 cleavage and hence the C3b concentration at the target surface (pathogen or stressed cell).The classical pathway is activated after the binding of the C1 complex to its targets that can be an antigen-antibody (IgG or IgM) immune complex or an apoptotic cell. The C1 complex is composed of C1q molecules and two different serine protease C1r and C1s . The hexCovalent deposition of C3b on the target cell by any of the three pathways induces opsonization, allowing the elimination of the pathogen/stressed cell by phagocytosis . When a Complement activation allows the formation of three different effectors: Opsonins  that can bind the target cell surface and promote its clearance. Anaphylatoxins (C3a and C5a) are released in the circulation and have an important role to induce inflammation and activate cells expressing anaphylatoxin receptors . C5aR1 and C5aR2 seem to have opposite effects, especially in the tumor context . MAC forComplement is a very powerful system that needs to be tightly regulated. To maintain the balance between complement activation on pathogens or altered host cells and inhibition on intact host cells, several regulators control each step of the proteolytic cascade  16]..16].The complexity of complement is not only due to its composition or its numerous functions (immune or non-immune) but also due to its ability to act extracellularly or intracellularly. Indeed, although complement is often described as a set of plasma proteins mostly produced by the liver and working in the extracellular compartment, recent studies showed a potential intracellular role of its proteins, especially in T cells. In these cells, intracellular C3 and C5 can be cleaved into C3a and C5a, impacting cell metabolism and homeostasis, the induction of a Th1 and CTL response but the contraction of the T-cell response .Furthermore, overactivation or deficiency of complement can trigger different pathologies, related to inflammation, coagulation, abnormal immune response, or abnormal cell clearance. A deficiency of some complement components can lead to an increased susceptibility to infections or auto-immune diseases . ComplemThe complement components are mostly produced by the liver, but it is important to note that both tumor and stromal cells also have the ability to produce complement proteins. Thus, their concentration inside the tumor is both due to the contribution of the systemic compartment and the local production by the different cell types.Analysis of complement gene expression in thirty different cancers revealed consistent patterns of expression: a high expression of genes coding for classical and alternative pathway; high expression of regulators and a low expression of the lectin pathway and the terminal pathway genes . These dIt seems that it is not possible to reach a general conclusion as for the pro or anti-tumor role of the complement system. This context-dependent action is reflected by numerous studies, sometimes contradictory, about complement and cancer. In a tumor context, it is not well understood how the complement system is activated, but several models show that the classical and alternative pathway components are found at a higher concentration in the tumor microenvironment . The tumIn the last decade, there was an increasing interest in the role of complement in cancer progression. Even if the classical functions of this system are to favor cell killing, its role in cancer appears to be mostly pro-tumoral. The first clue was the slower tumor growth in case of C3, C4 or C5aR deficiency in a TC1 cancer mouse model .Mouse models were, and still are, very useful to study the mechanisms of action and impact of complement on immune cells in the case of cancer. Nevertheless, mouse models yielded some contradictory findings, stressing the context-dependent role of complement in cancer. C3 and C3a are reported to play an important role in cancer progression. Indeed, several studies using syngeneic mouse models  revealed that C5a and its receptor C5aR1 are involved in the recruitment of MDSC. C5a can amplify their capacities to produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) creating an environment favorable for the suppression of the anti-tumor CD8+ T-cell mediated response . In addiAn important regulator of the intratumoral levels of C5a is PTX3; this molecule interacts with C1q and FH to modulate the local complement activation. PTX3 is described as an oncosuppressor in mouse models, inhibiting complement activation via FH recruitment, limiting the production of C5a and CCL2 (a pro-inflammatory chemokine) and avoiding the recruitment of tumor-promoting macrophages. The PTX3 deficiency leads to a chronic complement-mediated inflammation, favoring spontaneous skin carcinoma development in a mice model . On the This context-dependent role of the complement system is also true for the pro-inflammatory C3a and C5a molecules that can have anti-tumor functions and appear to be crucial for a good tumor response to radiotherapy . In a caThe complement system modulates the T-cell response in a tumor context but a role of complement proteins on the B cell response was also recently described. To be efficient, the chemotherapy has to induce a specific subset of B cells, the ICOS-L+ cells (Inducible T-cell Co-Stimulator Ligand) that express the Complement Receptor 2 (CR2). The interaction of C3 fragments with CR2 promotes the ICOS-L+ B cell generation. On the over hand, the over-expression of CD55 (a complement regulator) inhibits the complement activation and prevents the formation of ICOS-L+ B cell . In thisThe tumor cells have the ability to produce complement proteins that can stimulate tumor growth directly, independently of the cascade activation. Tissue staining and transcriptomic analysis reveal that in many cancers types the presence of complement proteins is associated with a worse outcome for the patient.C1q is a multitasking protein that has a strong direct impact on tumor cells, positively and negatively affecting their biology. In human prostate, breast, cancer or neuroblastoma, anti-tumor role of C1q is described, as an apoptosis inducer. C1q activates WWOX, a tumor suppressor gene, then the phosphorylated form of WOX1 accumulates in nuclei and sends anti-proliferative and pro-apoptotic signals ,53. ThisFH is mostly studied on lung and cSCC. In addition to protecting tumor cells from complement-mediated cytotoxicity, FH promotes cell migration . HoweverIn cSCC, knock-down of C1s, C1r, FB, FH and FI exerts similar effects on the tumor growth. These proteins seem to be implicated in the promotion of the tumor cell proliferation, migration, and survival, via the activation of the signaling pathways PI3K and Erk 1/2 ,56. In cThe recognition of the anaphylatoxins by their receptors  present at the surface of some tumor cells leads to the activation of the signaling pathways PI3K, Erk 1/2 and AKT. The activation of these pathways favors the proliferative, survival and invasive properties of tumor cell . The abiThe anaphylatoxins are not the only complement proteins involved in cancer progression. Most frequently in a tumor context, the complement activation is stopped before the formation of the MAC. Nevertheless, even when the lytic pore is assembled, the tumor cell could escape from the lysis by activating the PI3K, AKT, Erk1/2, p70 S6 kinase signaling pathways. This results in an inhibition of the apoptosis, and finally favors the tumor progression .Neo-angiogenesis is critical for the tumor growth, by supplying tumor cells with oxygen and nutriments. This parameter is directly linked to the tumor aggressiveness . RecentlTo conclude, the complement system is involved in the key processes of the tumor progression: immunity, angiogenesis and tumor cell proliferation and spreading. Depending of the cancer types and the complement molecule, various pro- and anti-tumoral functions are described . This muIn cancer, complement components can be up-regulated or down-regulated . Their oThe modifications of expression are not only found locally inside the tumor but also in the systemic compartment. This characteristic is important for cancer patients and could be helpful in the future to classify the patient and adapt the treatment with a blood test. Even if this perspective is interesting, it is important to note that an increase or decrease of protein expression in the systemic compartment does not necessarily mean that a similar modification occurs locally inside the tumor. The correlation between the situation inside the tumor and in the plasmatic compartment has to be studied to better understand the actions of complement proteins in a tumor context.The bioinformatic analysis, even if it needs biological confirmation, shows us that the tumors are not all equal in the context of complement activation. This has to be considered for the development of new complement-affecting anti-cancer therapy .Considering all the data, the complement inhibition and specifically the anaphylatoxins inhibition could be a promising treatment for patients with certain cancers. Currently, the only complement inhibitors approved are acting at the level of C5, such as Eculizumab . It alloThe anaphylatoxins receptors are present at the surface of the immune cells and at the surface of some tumor cells. C5a can interact with two different receptors, C5aR1 and C5aR2, with opposite functions. C5aR1 seems to have pro-tumoral role, whereas C5aR2 has more limited impact but tends to modulate the tumor growth .A common mechanism of action of the C5a-C5aR1 axis is to induce an immunosuppressive microenvironment by recruiting cells that will inactivate the effector T cells. Even if the immune checkpoint inhibitors (anti-PD1/PD-L1) have the ability to reinvigorate the exhausted effector T cells, they cannot reverse the immunosuppressive environment set up, explaining why these drugs are not working equally between patients . The posEven if C3aR and C5aR seem to be interesting targets for cancer treatment, it is important to recall that depending on the cancer their actions are not the same. Indeed, the study of the literature highlights cancer types with pro-tumor effects of C3aR/C5aR and others, with anti-tumor effects. The lung, colon, ovarian or breast cancer are often described as cancer with aggressive complement, implicated in the tumor development . In paraMonoclonal antibody (mAb)-based immunotherapy has shown promising results. Especially the anti-CD20 molecules in the context of hematological tumors. Their benefit is due in part to their ability to activate complement-dependent cytotoxicity through their Fc part . In thisIt has been demonstrated that a single amino acid substitution in the IgG-Fc domain favors the formation of IgG hexamers, called HexaBodies . These mAnother strategy is to use bi-specific antibodies. Such antibodies can recognize two different epitopes, for example one tumor-specific and the other one targeting complement membrane regulator. Bi-specific antibodies were recently developed to induce the complement cytotoxicity, by the recognition of the properdin  and the EGFR  . Even ifThese new ways to engineer antibodies open doors for very interesting combined therapies.The available data have to be taken with caution, as most of it comes from mouse models, which are not always in line with the human pathology. For example, mouse models of melanoma , sarcomaIt is very important to always evaluate the harm-benefit ratio. The different cancer types are not equivalent and, even inside the same type of cancer, the patients are not equal and a good treatment for one patient can be inefficient or even deleterious for others. The obvious risk of using complement inhibitors is that the killing of the tumor cells by the cascade, triggered by anti-tumor neoantigens antibodies, will be impaired. This mechanism could be operating in some contexts, such as the case of anti-FH antibodies in NSCLC . CancersOn the other part of the spectrum are the tumors in which complement overexpression correlates with poor prognosis , and in The results of the STELLAR-001 clinical trial  will be of great interest. Positive or negative results in lung and liver cancers may not necessarily be applicable to other cancers, for which separate studies have to be performed. Interestingly, liver cancer (HCC) belongs to the “Protective complement” group  , where tIn any case, due to the pleiotropic effects of complement, it is complicated at present to predict whether and to what extend complement modulation will be beneficial or harmful in patients with cancer. This is, therefore, an exciting area of research with a great future potential.Recent discoveries in the complement system are very challenging. The complement proteins act everywhere in the body, extracellularly and intracellularly, they have functions related to the complement activation or independent of it. This new understanding just adds to the already known complexity and plurality of this system. The actions of complement in the tumor context are diverse: action on the immune cells, on the cancer cells and also action on angiogenesis. What this review highlights is the complexity of these functions that can sometimes be opposite depending on the cancer type. It appears that the complement activation mostly has pro-tumor effects, but its complete inhibition may not be always desirable. Indeed, a good response to treatment (chemotherapy or radiotherapy) needs low level of complement activation for the setting of an anti-tumor immunity.To conclude, it appears clear that the complement system has to be considered for the development of new therapies. However, a large spectrum of complement modulators are entering the market, opening numerous possibilities in cancer therapy .


It was shown that for our SPV gas sensor device, using porous sputtered ZnO nanostructured thin films as the active gas sensing electrode material, the basic gas sensor characteristics in a toxic NO2 gas atmosphere are strongly dependent on the target NO2 gas flow rate. Moreover, it was also confirmed that our SPV gas sensor device is able to detect the lowest NO2 relative concentration at the level of 125 ppb, with respect to the commonly assumed signal-to-noise (S/N) ratio, as for the commercial devices. In this work the characteristics of a novel type of room temperature NO After more than six decades of development only a few types of gas sensors devices have been constructed. These are based on a variety of chemical and physical methods including electrochemical, catalytic, optical, acoustical and electrical designs. Reviews of the most common types of gas sensors include, among others, those of Comini et al  and by XAmong the electrical methods, the most common conductometric type gas sensor devices (systems) are based on semiconductor metal oxides (MOX), organic materials, carbon nanotubes and conductometric polymers. However, even after five decades of development, they still exhibit some critical and fundamental limitations, such as high-temperature working conditions and related high power consumption. These sensors do have good sensitivity; depending on the gas, usually at the level of ppm, but this is combined with a rather poor selectivity ; in addition, they possess rather poor dynamic parameters (long response and recovery times) ,10,11,12In order to overcome the above-mentioned crucial limitations of conductometric MOX gas sensors, some innovative ideas and related approaches have appeared in the literature in recent years describing improvements of their sensing abilities. One of these methods exploits the effect-of-work function ) variation, which can be measured by using the Kelvin vibrating capacitor as a transducer ,14. HoweThis type of sensor can be improved by using the additional external illumination of the gas sensor material to play the role of measuring electrode, a phenomenon commonly known the surface photovoltage (SPV) effect . However2 atmosphere in relative concentrations of up to 1 ppm in synthetic air have been verified and interpreted on the basis of information on local surface chemistry and morphology of porous ZnO nanostructured thin films. In our recent paper , we have2 at constant relative concentration in synthetic air on the variation of SPV amplitude versus time, as well as the respective gas sensor dynamic parameters, such as response and recovery times. The influence of gas flow rate at constant relative concentration on the gas sensor response characteristics has recently been investigated by several groups, among others by Eklöv et al. [2 detection, by Lezzi et al. [2 film-based conductometric sensor for CO detection, by Utriainen et al. [2 film-based conductometric sensor mainly for CO detection, by Gmür et al. [3 gas sensors for breath analysis.In this paper the results of systematic studies of the usable gas-sensing characteristics of our new SPV gas sensor device are presented, including the determination of the influence of gas flow rate of NOv et al.  for the i et al.  for the n et al.  in the cn et al.  for SnO2r et al.  for the r et al.  for port2 in synthetic air well below 1 ppm level at the chosen middle constant gas flow rate, to attain the lowest NO2 relative concentration that can be experimentally detected at the commonly assumed signal-to-noise (N/S) ratio of 3.Moreover, we have determined the variation in amplitude of the SPV signal with decreasing relative concentrations of NOIn our experiment the recently elaborated SPV gas sensor device  was used2 relative concentration in dry synthetic air significantly below the ppm level we used a novel gas dilution, mixing and dosing system, that was designed by our group and constructed by the MEDSON Company . Its simplified schematic idea is shown in For the determination of the lowest NO-2 toxic gas at two different starting concentrations in synthetic air , combined with a set of respective cut-off valves; two bottles and related stainless steel channels of NO-the gas dilution, mixing and dosing parts based on gas mass flow controllers (MFC)–model Brooks SLA5850  combined with a set of respective cut-off valves;-2 gas mixture in the synthetic air;gas mixing chamber with a set of baffle peers to reach the well defined precise final constant relative concentration of NO-2 toxic gas mixture to the surrounding atmosphere).“back pressure” unit based on the gas mass flow controllers (MFC)–model Brooks SLA5820  as the pressure regulators, combined with two exhaust systems equipped with additional toxic gas washing bottles .2 gas flow rate in combination with the specific NO2 relative concentration in synthetic air reaching the SPV gas sensor measuring chamber. It consists of two independent steps, i.e. the controllable value of the NO2 gas flow rate which was achieved by using the above described gas dilution, mixing and dosing system (MEDSON), whereas the controllable NO2 relative concentration was achieved by using additionally the GasAlert Extreme NO2 detector . For the evaluation of relative NO2 concentration below 1 ppm (its detection threshold) an extrapolation procedure was used. Finally, between the subsequent gas sensing measurements the SPV gas sensor measuring chamber was rinsed with pure synthetic air for 30 min. It should be underlined that in our experiments we used a gas handling procedure allowing the repeatable measuring conditions defined by the specific NO-2 gas flow rate at constant relative concentration on the gas sensor response characteristics, together with basic gas sensor dynamic parameters;determination of the influence of NO-2 relative concentration that can be detected by our SPV gas sensor device with respect to the commonly used signal-to-noise (S/N) ratio, one of the most important usable parameters for most commercial gas detection systems.determination of the lowest NOIn our research, we have focused on the working conditions of our highly sensitive SPV gas sensor prototype, which can be divided in the following two steps:2 adsorbed at the surface of the gas sensor material also increases. This can be a cause of the variation of shape of response curve towards the corresponding higher response time, as well as the shape of recovery curve towards the corresponding higher recovery time directly related to the favorable conditions for the gas desorption. Thus, in our study we have determined the influence of NO2 gas flow rate at constant concentration in synthetic air on the above-mentioned gas sensor response characteristics, together with basic gas sensor dynamic parameters like response and recovery time.In general, taking into account the dynamic aspects of gas adsorption/desorption effects at the surface of gas sensor materials, the gas-sensing characteristics should strongly depend on the flow rate of target gas reaching the gas sensor system measuring chamber. This is related to the fact that with an increased flow rate, the amount of NO2 gas flow rate in the range of 100 ÷ 20 mL/min, at the constant relative NO2 concentration of 20 ppm in the standard dry synthetic air (with respect to the level in the synthetic air).2 relative concentration of 20 ppm in the standard dry synthetic air) the amplitude of SPV signal decreases only by a factor of less than 2, taking into account the average accuracy of determination of variation of SPV signal at the level of about a single mV, which corresponds to the signal-to-noise (S/N) ratio at the level of 3. The obtained data are summarized in the One can observe from our SPV gas-sensing characteristics that with the lowering of gas flow rate in the range of 100 ÷ 20 mL/min  of respective gas sensor curves, directly related to the variation of gas sensor dynamic parameters like response and recovery time(s), respectively. 2 gas flow rate of 60 mL/min, at the constant relative NO2 concentration of 20 ppm in the standard dry synthetic air, and respective gas sensing characteristics including dynamic parameters. 2 gas flow rate of 60 mL/min, at the constant relative concentration of 20 ppm in the standard dry synthetic air, was ~240 s and ~1400 s, respectively. The respective values of the above-mentioned dynamic parameters estimated for the various gas flow rates are also summarized in 2 gas adsorbed at the surface of gas sensor materials, and from a second one, to the more favorable conditions for the desorption of various amounts of NO2 gas from the surface of gas sensor materials under the synthetic air exposure at gas flow rate 60 mL/min.As shown in 2) used in our experiments was only physically adsorbed onto the inner surfaces of the ZnO nanostructured thin films used as the gas sensor material. In such conditions a better dynamic characteristics could not be expected. Nevertheless, these dynamic characteristics are better than those of the commonly used conductometric gas sensors for which the response signal at room-temperature working conditions are usually close to the signal-to-noise ratio. Of course, one can expect that recovery time of our gas sensor system will be lowered , but only after application of the additional electrode degassing mechanism . However, the main advantage of our SPV gas sensor system would be lost. Moreover, further study is required in order to optimize the degassing conditions of the target gas, which are currently in progress.However, it should be noticed that these values have been obtained for our SPV gas sensor system at room temperature. Crucially, it directly confirms that the target gas  ratio. As our second objective we concentrated on determining the lowest NO2 target gas below 1 ppm in the standard dry synthetic air, at the mean NO2 gas flow rate of 60 mL/min.2 is accompanied by a decreased relative amplitude in the SPV signal, reaching its lowest value for of NO2 at the level of 125 ppb, taking into account the commonly used criteria that the level of signal-to-noise (S/N) ratio should not be lower than 3. Crucially, this value was already reached at room temperature, which looks very promising with respect to the performance of commonly used conductometric type gas sensor systems. For instance, similar experiments have been performed by Procek et al. [2 at room temperature, that can be compared with our results. The obtained response was 304 ± 74 (%), which corresponds to similar signal-to-noise (S/N) ratio ≈ 4, as used in our analysis.As can be seen from k et al.  for the 2 in the synthetic air. In addition to the above, it should be noted that, from our SPV gas-sensing characteristics shown in 2 at the constant relative concentration in the synthetic air shown in Of additional importance, the respective recovery time(s) are similar at the level of about 1000 s, and comparable with the gas response time(s). It corresponds to the respective gas sensor dynamic parameters for the gas response curves at lower gas flow rates of NOIn this study the working conditions of our novel, high-sensitivity gas sensor device using the surface photovoltage effect, based on the Kelvin probe approach, have been elaborated. 2 at the constant relative concentration of 20 ppm on the sensor response and recovery times, respectively, as well as on the determination of lowest relative NO2 concentration below 1 ppm relative concentration in synthetic air that can be detected with this sensor.We have focused on the determination of the influence of gas flow rate of NOFirstly, it was observed that with the lowering of target gas flow rate in the range of 100÷20 mL/min, the amplitude of SPV signal decreases only by a factor of less than 2, taking into account the average accuracy of determination of variation of the SPV signal at the level of about single mV. Moreover, a slight variation in the shape of respective gas sensor curves was observed directly related to a variation of gas sensor dynamic parameters, and almost twice decreasing of the respective response/recovery time(s) was determined.2 in the standard dry synthetic air, an evident tendency towards decreasing of the relative SPV signal appears, reaching at room temperature a smallest relative NO2 concentration at the level of 125 ppb, with respect to signal-to-noise (S/N) ratio at the level of 3. Moreover, the gas sensor response time(s) are similar to the respective recovery time(s) being at the level of about 1000 s.Secondly, it has been established that, with the lowering of relative concentration of NOThis study confirms that our SPV gas sensor device  has the


Child undernutrition in India remains widespread. Data from the National Family Health Survey 3 and 4 (NFHS-3 and NFHS-4) suggest that wasting prevalence has increased while stunting prevalence has declined.1) describe wasting and stunting by month of measurement in India in children <5 y of age in NFHS-3 and NFHS-4 surveys, and 2) test whether differences in the timing of anthropometric data collection and in states between survey years introduced bias in the comparison of estimates of wasting and stunting between NFHS-3 and NFHS-4.The objectives of this study were to do the following: Data on wasting and stunting for 42,608 and 232,744 children aged >5 y in the NFHS-3 and NFHS-4 survey rounds were analyzed. Differences in the prevalence of wasting and stunting by month of year and by state of residence were examined descriptively. Regression analyses were conducted to test the sensitivity of the estimate of differences in wasting and stunting prevalence across survey years to both state differences and seasonality.P = 0.2) and a negative difference in stunting prevalence , indicating a small bias for wasting but not for stunting in unadjusted analyses.Examination of the patterns of wasting and stunting by month of measurement and by state across survey years reveal marked variability. When both state and month were adjusted, regardless of the method used to account for sample size, there was a small negative difference from 2005–2006 to 2015–2016 in the prevalence of wasting (−0.8 ± 0.6 percentage points; State and seasonal differences may have introduced bias to the estimated difference in prevalence of wasting between the survey years but did not do so for stunting. Future data collection should be designed to maximize consistency in coverage of both time and place. Physical growth is a useful and widely accepted marker of child health and nutritional status. In India, child undernutrition, assessed as attained growth, is widespread. According to the National Family Health Survey-4 (NFHS-4), the nationwide prevalences of wasting, stunting, and underweight in children <5 y of age in 2015–2016 were 21.0%, 38.4%, and 35.8%, respectively  and within states (across surveys). A comparison between the 2 surveys of the timing of data collection and the states where the data were collected reveals varying degrees of overlap in the months of data collection , 2. The The objectives of this study were therefore to describe wasting and stunting by month of measurement in India in children <5 y of age in the NFHS-3 and NFHS-4 surveys, and to estimate the magnitude of any bias introduced in the comparison of estimates of wasting and stunting between the NFHS-3 and NFHS-4 surveys by differences between survey years in the timing of anthropometric data collection and in the states where data were collected.z score , height-for-age z score , and weight-for-age z score (<−6 or >5), as recommended by WHO  estimated from a set of multiple regression models that either excluded or included state and month of measurement. Specifically, to examine whether estimation of the difference in prevalence from 2005–2006 to 2015–2016 was affected by month of measurement, regression analyses were conducted to test the sensitivity of the estimate of the difference in wasting and stunting prevalence across survey years to both state differences and seasonality . In these regression models, the dependent variable was the prevalence of wasting or the prevalence of stunting for children. The observations in the data set were wasting and stunting prevalence by year, state, and month, which were calculated accounting for household sampling weights. Year (2005–2006 or 2015–2016), state, and month of year were considered as nominal, fixed-effect, independent variables. These regression models produced theoretically unbiased estimates of coefficients despite the empty cells in the data matrix defined by state and year under the assumption of no interaction between state and month  months when data were collected in both survey years (December–August) and 2) states where data were collected in both survey years (6 states excluded). These analyses necessarily assumed that that there were no interactions among year, state, and month since the data did not allow tests of potential interactions.Analyses conducted at the aggregate level for the state were replicated at the individual level using procedures for complex samples that incorporated the primary sampling units and household weights. Household weights were normalized within each year before pooling the weights. In addition to models that accounted for year, year and state, year and month, and all 3, a model was run further adjusting for child's age, sex, state, caste of the mother, religion of mother, any morbidity, having no toilet, education of mother, place of residence, and mother's age. These variables were chosen because they are known risk factors for poor child growth outcomes . Data weThe weighted prevalence of wasting in India was lower (15–17%) between December and February in both survey years and then increased (18–23%) between March and May in both survey years  (P = 0.082). The P values for year in each of the 4 models were ≥0.08. Examination of the root mean square errors and percentage of variance explained for each model showed that year alone explained little of the variance in wasting prevalence, month explained a modest amount of the variance, and state explained a substantial amount of the variance. The results from the 2 robustness analyses that restricted the sample were essentially the same as those reported here (not shown). Analyses replicated at the individual level showed a pattern similar to that observed in analyses at the aggregate level, but with lower P values . In the NFHS-4 survey, the weighted prevalence of stunting remained relatively stable throughout the year (about 37% stunted) . , where data can only be collected in some locations during some seasons. The 2019 WHO/UNICEF report on recommendations for the data collection of anthropometric indicators in children <5 y of age suggests that during survey planning, researchers “identify the best period to implement the survey to allow comparison with previous surveys,” but provides little guidance for the practical implications of this suggestion . The bes