Chronic exposure to antigens may favor the production of IgG4 antibodies over other antibody types. Recent studies have shown that up to a 30% of normal human IgG4 is bi-specific and is able to recognize two antigens of different nature. A requirement for this specificity is the presence of both eliciting antigens in the same time and at the same place where the immune response is induced. During transmission of most vector-borne diseases, the pathogen is delivered to the vertebrate host along with the arthropod saliva during blood feeding and previous studies have shown the existence of IgG4 antibodies against mosquito salivary allergens. However, there is very little ongoing research or information available regarding IgG4 bi-specificity with regard to infectious disease, particularly during immune responses to vector-borne diseases, such as malaria, filariasis, or dengue virus infection. Here, we provide background information and present our hypothesis that IgG4 may not only be a useful tool to measure exposure to infected mosquito bites, but that these bi-specific antibodies may also play an important role in modulation of the immune response against malaria and other vector-borne diseases in endemic settings. Infectious diseases are one of the leading causes of mortality worldwide , 2. FromAs a general characteristic, IgG4 is an effective immuno-regulator . This isbi-specificity is that both eliciting antigens must be present at the same time and at the same place when the immune system is stimulated  –54. The Bi-specific IgG4 molecules are stimulated in an environment of diverse antigens. For example, previous studies have shown that a single IgG4 molecule is able to bind grass/pollen antigens and house dust mite antigens at the same time . In the The human immune response against vector-borne pathogens often involves the production of IgG1 antibodies with high pro-inflammatory activities that are able to clear most pathogens. If conformational changes are induced at the Fc portion of an antigen-bound IgG1 molecule, a significant IgG4-mediated response against SPs and/or pathogen antigens may block an IgG1-mediated response, which would have a profound effect on the fate of infectious disease progression and immune response Thus, IgG4 and bi-specific IgG4 antibodies may represent attractive examples of how the immune response to environmental antigens could potentially modulate the fate of infectious diseases in humans .Dracunculus medinensis, all filarial worms use insects as intermediate hosts  is group of parasitic infections often transmitted by arthropods to humans and animals –62. Withte hosts . These dte hosts . Howeverte hosts .Aedes, Anopheles, Culex, and Mansonia can all transmit filarial parasites. Whether bi-specific antibodies are elicited against salivary/pathogen antigens in filariasis or other helminthic diseases remains to be investigated, though it seems a likely scenario.As in the rest of human helminthiasis, IgG4 antibody response is the hallmark of filarial infections. Previous studies have shown that up to 95% of IgG antibodies against filarial worms belong to the IgG4 subclass , 67. FilPrevious studies demonstrate that the levels of IgG antibody subclasses during infection depend on filarial transmission intensity. In higher transmission areas, antigen-specific IgG4 levels against different parasite stages (microfilaria versus adults stages) are associated with parasite carriage and asymptomatic infection , 69, In Plasmodium , a small proteins exclusively expressed in adult female salivary glands that plays a role blood feeding  and Lutzomyia spp. (New World) sandflies (Leishmania donovani (Asia) and L. infantum/L. chagasi with more than 200 million people at risk globally ] caused by parasites of the genus andflies , 96. Cutandflies . In factandflies . High anandflies . VL is aglobally , 100. Th from VL . It has  from VL . Higher  from VL . Additio from VL .It has been well documented that saliva from sandflies enhances Leishmania infection during the first stages of the infection. This is thought to be due to the immunosuppressive effect of several saliva components on macrophages and T cells –108. IntPh. papatasi sandfly , which is transmitted by  regions . While t regions . It is t regions –123. Dur regions . ADE is  regions , 126. Si regions , it is iCurrently, considerable research in DENV pathogenesis is focused on pathogen-induced disease severity –130. AltLu. longipalpis sandflies in Brazil  and control (n = 6) human subjects living in an area where Ae. aegypti is the main vector of DENV, and Ae. albopictus was recently introduced. Samples were tested for the presence of IgG4 antibodies in an ELISA-based assay (Figure Ae. aegypti SP is the IgG4, consistent with previous studies (Aedes SP. We found that our serum samples did contain bi-specific IgG4 antibodies (Figures Ae. aegypti SP than Ae. albopictus SP (Figures Ae. aegypti. We are currently isolating the hybrid IgG4 molecules from these samples to test their effect on DENV infection.In a given area, people may be exposed to hundreds of mosquito bites from different mosquito species . Previouy Figure A. Our re studies , 71. We  Figures B,C. We a Figures B,C. HoweOur experiments suggest the existence of IgG4 molecules binding DENV and SP, and they are an approximation of the effect of immunity against mosquito saliva in viral infections. More specific and accurate testing must be done to evaluate single bi-specific IgG4 antibodies and demonstrate the role of hybrid IgG4 molecules in vector-transmitted diseases.It is of pivotal importance to determine whether there is production of saliva-pathogen IgG4 bi-specific antibodies during human infection with vector-borne pathogens, as well as the SPs that are involved in such a response. We speculate that in order to reach protective immunity against diseases, such as malaria through vaccination, treatment options should induce and resemble the natural immunity-building experience undergone by individuals living in areas with intense malaria transmission.The study of the role of mosquito saliva immunity and antibodies against both pathogen and vector, as a tool to evaluate and monitor the exposure to infected mosquito bites, would improve control interventions and guide new strategies for protection and elimination. We have presented here evidence that IgG4-mediated responses are present in vector-borne diseases and that both arthropod saliva and the immune response against it may favor the formation of pathogen/mosquito bi-specific IgG4 antibodies. We hypothesize that bi-specific IgG4 is formed during chronic exposure to both mosquito bites and pathogen infection. Extensive additional research is necessary to characterize the nature of bi-specific antibodies and what role they may play in pathogenesis of or protection against vector-borne diseases.A written approval for collection of human samples was approved by Universidad de Pamplona, Los Patios Hospital and the Ethics Review Board of Hospital Erasmo Meoz.Dr. Londono-Renteria is a Research Associate at Dr. Colpitts’ Laboratory. This laboratory focuses on Dengue infection and pathogenesis studies as well as research on mosquito factors involved in the enhancement of transmission of vector-borne diseases.BL-R, AT, and TC were involved in the bibliography search and the manuscript writing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The dataset helps the readers to understand and evaluate the potential of POFA though a waste material can be used as a replacement of Portland cement in having durability properties at an acceptable range.Datasets contained in this article are outcomes of the durability properties carried out on Palm Oil Fuel Ash (POFA) concrete specimens to determine the effect of acid attack, Sulphate resistance, water absorption and rapid chloride permeability. Specimens were immersed in 1% hydrochloric acid (H Specifications TableValue of the data•The data contained herein can be used to solve some of the problems of durability of concrete in the cement industries.•The data can be used to determine durability behaviour of self compacting concrete (SCC) •The employed approach can serve as benchmark to other methods in testing properties of SCC.•The dataset can be used to determine performance required for concrete structure.•The dataset can serve as an experimental framework for the analysis of other basic properties of concrete.1In this dataset article, durability test, acid attack, sulphate, water absorption test, rapid chloride permeability test on POFA self-compacting concrete test were carried out while the test results are as contained in 22.1The results of acid attack in terms of weight loss after 90 days for all the concrete are shown in 2.2External sulphate attack to cementious matrix is a complex process that involves the movement of sulphate ions through the pores by means of different mechanisms of transportation and the interaction of aggressive solution with some compounds of cements paste to form expansive compounds (gypsum) that produce cracking, strength loss and softening. After 28 days of curing the test was conducted by measuring the weight losses of the specimen at 28, 56 and 90 days. 2.3The result of Saturated Water Absorption (SWA) tests of various self-compacting concrete mixes at the ages of 28, 56 and 90 days are given in 2.4In the text, SCC and NC denote self compacting concrete and normal concrete (without POFA) respectively.It was observed that the incorporation of palm oil fuel ash in self-compacting concrete enhanced the Sulphate and acid attack. The rapid chloride and water absorption showed a reduction in weight. It can also be seen that both normal concrete as well as SCC palm ash have all been following the same trend. In


Activation of c-Met, a receptor tyrosine kinase, induces radiation therapy resistance in non-small cell lung cancer (NSCLC). The activated residual of c-Met is located in lipid rafts . Therefore, we hypothesized that disturbing the integrity of lipid rafts would restrain the activation of the c-Met protein and reverse radiation resistance in NSCLC. In this study, a series of experiments was performed to test this hypothesis.NSCLC A549 and H1993 cells were incubated with methyl-β-cyclodextrin (MβCD), a lipid raft inhibitor, at different concentrations for 1 h before the cells were X-ray irradiated. The following methods were used: clonogenic (colony-forming) survival assays, flow cytometry , immunofluorescence microscopy (to show the distribution of proteins in lipid rafts), Western blotting, and biochemical lipid raft isolation (purifying lipid rafts to show the distribution of proteins in lipid rafts).Our results showed that X-ray irradiation induced the aggregation of lipid rafts in A549 cells, activated c-Met and c-Src, and induced c-Met and c-Src clustering to lipid rafts. More importantly, MβCD suppressed the proliferation of A549 and H1993 cells, and the combination of MβCD and radiation resulted in additive increases in A549 and H1993 cell apoptosis. Destroying the integrity of lipid rafts inhibited the aggregation of c-Met and c-Src to lipid rafts and reduced the expression of phosphorylated c-Met and phosphorylated c-Src in lipid rafts.X-ray irradiation induced the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts through both lipid raft-dependent and lipid raft-independent mechanisms. The lipid raft-dependent activation of c-Met and its downstream pathways played an important role in the development of radiation resistance in NSCLC cells mediated by c-Met. Further studies are still required to explore the molecular mechanisms of the activation of c-Met and c-Src in lipid rafts induced by radiation.The online version of this article (10.1186/s12885-018-4501-8) contains supplementary material, which is available to authorized users. Radiotherapy alone or combined with chemotherapy is the foundation for treating various solid tumors. However, radiation resistance greatly limits the curative effect of radiotherapy, which becomes one of the most important reasons for local recurrence and metastasis. Therefore, reversing the resistance of radiotherapy and increasing the radiosensitivity become the toughest challenge in cancer treatment.Lipid rafts are special microdomains in the plasma membrane that influence cell proliferation, apoptosis, angiogenesis, immunity, cell polarity, and membrane fusion , 2. c-MeHuman NSCLC cell line A549  was obtained from the Cell Bank of the Chinese Academy of Sciences and H1993  was obtained from the American Type Culture Collection (ATCC). Methyl-β-cyclodextrin (MβCD) was purchased from Meilun Biotechnology . Antibodies against c-Met, c-Src and β-actin were purchased from Wanlei Biotechnology . Antibodies against phosphorylated (p)-c-Met and p-c-Src were obtained from Bioss Inc. . Anti-flotillin-1 antibody was obtained from Boster Biotechnology . Fluorescein isothiocyanate-conjugated-anti-cholera toxin subunit B was purchased from Sigma . Horseradish peroxidase-conjugated specific goat anti-rabbit secondary antibody, Cy3-labeled goat anti-rat c-Met antibody, Cy3-labeled goat anti-rat c-Src antibody, phenylmethanesulfonyl fluoride (PMSF), radioimmunoprecipitation assay (RIPA) lysis buffer, SDS, trypsin and a cell cycle analysis kit were purchased from Beyotime Biotechnology . A cell apoptosis analysis kit was purchased from Nanjing Keygen Biotechnology .The following instruments were used: a linear particle accelerator used for human radiotherapy ; a flow cytometer ; a low-temperature refrigerated centrifuge ; a dual-gel vertical protein electrophoresis apparatus ; a gel imaging system ; a fluorescence microscope ; and a Beckman SW40 rotor .A549 and H1993 cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) at 37 °C under 5% carbon dioxide conditions. Cells were routinely subcultured in a monolayer, digested with 0.25% trypsin and stopped with DMEM when the cells covered 90% of the culture bottle. Then, the cells were cultured in FBS-free medium for another 24 h and prepared for various treatments.MβCD is a cyclic polysaccharide containing a hydrophobic cavity that enables the extraction of cholesterol from cell membranes . CholestClonogenic survival assays described by Franken et al.  were use6/ml were exposed to either control DMEM or 5 or 10 mM MβCD for 1 h followed by X-ray irradiation (8 Gy) or control irradiation (0 Gy) then cultured in fresh DMEM. Cells were harvested and fixed in ice-cold 70% ethanol (4 °C) after being cultured for 4, 8, or 24 h. For cell cycle assays, after staining with 25 μl propidium iodide , the samples were incubated with 10 μl RNase A for 30 min in the dark at 37 °C. Cell apoptosis assays were performed with 5 μl PI for 15 min in the dark at 37 °C after mixing with 5 μl Annexin V-FITC. Cell cycle and apoptosis were evaluated by flow cytometry , and the data were analyzed with BD Accuri C6 Software 1.0.264.21.Cell cycle and apoptosis analysis were performed with flow cytometry assays. Cells at a density of 2 × 10Cells were plated on Lab-Tek chamber slides. After treatment with MβCD or control for 1 h followed by irradiation at 0 or 8 Gy, cells were fixed with 4% paraformaldehyde at 37 °C for 15 min, permeabilized with 0.5% Triton-X 100 after washing with PBS three times and then blocked with goat serum for 15 min. For lipid raft staining, cells were incubated with 0.05 mg/ml fluorescein isothiocyanate-conjugated-anti-cholera toxin subunit B for 1 h. For c-Met and c-Src staining, cells were incubated with anti-c-Met (Cy3-labeled) or anti-c-Src (Cy3-labeled) for 1 h then washed and blocked. 4′,6-Diamidine-2′-phenylindole dihydrochloride (DAPI) was used to stain the nuclei. Imaging was performed via fluorescence microscopy.w/v) skim milk in Tris-buffered saline-Tween 20  for 1 h at 37 °C. Membranes were incubated overnight at 4 °C with primary antibodies against c-Met, p-c-Met, c-Src, p-c-Src and β-actin. After the overnight incubation, membranes were incubated with the appropriate horseradish peroxidase-conjugated specific goat anti-rabbit secondary antibody for 45 min and then washed with TTBS six times. The blots were developed by enhanced chemiluminescence followed by exposure to film, and the optical density values of target blots were analyzed with Gel-Pro-Analyzer software.Western immunoblotting analysis was performed as previously described . Briefly7 cells in six 100-mm plates. Treated and untreated cells were washed twice with cold PBS, scraped into 2 ml of TNE solution  and incubated for 40 min. The samples were scraped and homogenized completely by passing through a 5-ml needle 40 times. Homogenates were mixed with 2 ml of 90% (w/v) sucrose and placed at the bottom of a 15-ml ultracentrifuge tube. A 5–35% (w/v) discontinuous sucrose gradient was formed above the homogenate-sucrose mixture with a 4-ml layer of 35% sucrose followed by a 4-ml layer of 5% sucrose by adding sucrose solution along the tube wall gently and slowly while avoiding any shake during the whole process. Next, samples were centrifuged at 39000 rpm at 4 °C for 20 h in a Beckman SW40 rotor. Twelve 1-ml gradient fractions were collected from the top of the gradient. Each fraction with no MβCD treatment and no irradiation was separated via SDS-PAGE and established the expression of flotillin-1, c-Met, p-c-Met, c-Src, p-c-Src by Western blot analysis. Fractions 2–6 were determined to be lipid raft fractions due to the presence of the lipid raft-specific protein flotillin-1  for 1 h followed by X-ray irradiation to a dose of 0 or 8 Gy. Sixteen hours later, the distribution of c-Met and c-Src in lipid rafts was determined , c-Src and p-c-Src (activated c-Src) in the whole-cell samples were significantly increased after X-ray irradiation , heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Smaller lipid rafts can stabilize their structure and form a larger platform through protein-protein and protein-lipid interactions . As a “hIn this study, the clonogenic survival assays showed that X-ray irradiation inhibited the proliferation of A549 and H1993 cells in a radiation dose-dependent manner regardless of MβCD pretreatment. Our results further confirmed that inhibiting the integrity of lipid rafts suppressed the proliferation of A549 and H1993 cells whether followed by X-ray irradiation or not. Furthermore, we found the proper concentration of MβCD (10 mM) and the proper radiation dose (8 Gy) for our remaining experiments.Next, we found that pretreating A549 and H1993 cells with 10 mM MβCD alone obviously increased the apoptosis rate in both control (0 Gy) and irradiated cells (8 Gy) but not for 5 mM MβCD alone. Our results also showed that the combined treatment of MβCD and radiation significantly increased the apoptosis rates of A549 and H1993 cells when compared with those of radiation alone at 4, 8 and 24 h, but this effect was not significant for the combination of 5 mM MβCD and radiation (8 Gy) compared with radiation alone. These results suggest that disturbing the integrity of lipid rafts by MβCD sensitized A549 and H1993 cells to radiotherapy in both time-dependent and concentration-dependent manners. Our findings also indicate that lipid rafts play an important role in increasing the radiation sensitivity of NSCLC cells, and the combination of MβCD and radiation may provide a new effective therapeutic strategy for the treatment of radiation-resistant NSCLC.To investigate the impact of X-ray irradiation on the redistribution of c-Met and c-Src in lipid rafts, A549 cells were treated with 10 mM MβCD or DMEM for 1 h followed by X-ray irradiation to a dose of 0 or 8 Gy, and the distribution of c-Met and c-Src in lipid rafts was determined 16 h later. The results showed that X-ray irradiation induced the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts. The results also demonstrated that destroying the integrity of lipid rafts restrained both the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts. These results indicate that X-ray irradiation-induced redistribution of c-Met and c-Src in lipid rafts might result in radiation resistance in NSCLC cells.Western blotting results showed that X-ray irradiation significantly increased the expression of c-Met, p-c-Met, c-Src and p-c-Src in the whole-cell samples, but this up-regulation was blocked by pretreatment with MβCD. The sucrose density gradient centrifugation analysis showed that X-ray irradiation significantly induced the accumulation of c-Met, p-c-Met, c-Src and p-c-Src to lipid rafts. Furthermore, the accumulation of these four proteins to lipid rafts was blocked by pretreatment with MβCD. Interestingly, we also found that the expression levels of p-c-Met and p-c-Src in the whole-cell samples were significantly increased in the combined group compared with those in the MβCD alone group. However, there was no significant change in the accumulation of these two proteins to lipid rafts. The percentages of p-c-Met and p-c-Src expressed in lipid rafts out of the whole-cell samples was obviously decreased in the combined treatment group when compared with those in the MβCD alone group. Collectively, these results show that X-ray irradiation might activate c-Met and c-Src through both lipid raft-dependent and lipid raft-independent mechanisms.By analyzing the percentages of c-Met, p-c-Met, c-Src, and p-c-Src proteins expressed in lipid rafts out of the whole-cell samples, we found that in A549 cells, the expression of p-c-Met and p-c-Src in lipid rafts induced by X-ray irradiation was significantly higher than that of c-Met and c-Src. Furthermore, the inhibition of p-c-Met and p-c-Src expressed in lipid rafts was more obvious than that of c-Met and c-Src by the destruction of lipid rafts.In summary, this study confirmed that MβCD suppressed the proliferation of human NSCLC cell lines A549 and H1993 with or without X-ray irradiation, and the combination of MβCD and radiation resulted in additive increases in the apoptosis of A549 and H1993 cells. X-ray irradiation induced the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts through both lipid raft-dependent and lipid raft-independent mechanisms. Our results also demonstrated that destroying the integrity of lipid rafts significantly inhibited the aggregation of c-Met and c-Src to lipid rafts. More importantly, the expression of p-c-Met and p-c-Src in lipid rafts induced by X-ray irradiation was notably higher than that of c-Met and c-Src. Furthermore, the inhibition of p-c-Met and p-c-Src expressed in lipid rafts was more obvious than that of c-Met and c-Src by destruction of lipid rafts.Taken together, we draw a conclusion that lipid rafts serve as the signaling platforms for the lipid raft-dependent activation of c-Met and c-Src induced by X-ray irradiation. The lipid raft-dependent activation of c-Met and its downstream pathways play an important role in radiation resistance of NSCLC cells mediated by c-Met. Destroying the integrity of lipid rafts can reverse these signaling pathways and improve the radiosensitivity of NSCLC cells, which can provide a new strategy for developing radiation sensitizing agents and for improving the therapeutic effect of radiotherapy. Further studies are still required to explore the molecular mechanisms of the activation of c-Met and c-Src in lipid rafts induced by radiation.Additional file 1:Table S1. Colony-plating efficiency (PE) of A549 cells treated with either control or MβCD followed by irradiation. (DOC 28 kb)Additional file 2:Table S2. Colony-plating efficiency (PE) of H1993 cells treated with either control or MβCD followed by irradiation. (DOC 29 kb)Additional file 3:Table S3. Expression of proteins in the whole-cell samples under different conditions in A549 cells. (DOC 28 kb)Additional file 4:Table S4. Expression of proteins in lipid rafts under different conditions in A549 cells. (DOC 28 kb)Additional file 5:Table S5. The percentage of protein expressed in lipid rafts out of the whole-cell samples in A549 cells. (DOC 28 kb)


Mesoporous solids, which were prepared from inorganic-surfactant mesostructured materials, have been investigated due to their very large surface area and high porosity, pore size uniformity and variation, periodic pore arrangement and possible pore surface modification. Morphosyntheses from macroscopic morphologies such as bulk monolith and films, to nanoscopic ones, nanoparticles and their stable suspension, make mesoporous materials more attractive for applications and detailed characterization. This class of materials has been studied for such applications as adsorbents and catalysts, and later on, for optical, electronic, environmental and bio-related ones. This review summarizes the studies on the chemistry of mesoporous silica and functional guest species (host–guest chemistry) to highlight the present status and future applications of the host–guest hybrids. Surfactant aggregates (surfactant mesophases) were found to be useful to produce mesoscopic structures. The preparation method, characterization and application of mesoporous silicas and other mesostructured and mesoporous solids have been a hot topic in current materials chemistry after the discovery of mesoporous silicas . The periodic mesostructures are prepared by the complexation of silica source with such surfactants as quaternary ammonium salts and block co-polymers as templates (structure directing agents) . The inoIn addition to the structural and the compositional variations mentioned above, the morphosyntheses have mesoporous silicas more attractive for application in optics, electronics, and medical and biological fields , 4, 15. in situ formation (polymerization and growth) in the mesopore. It is also possible to obtain hybrids by co-precipitation (co-polymerization) of guest species with silica sources during the synthesis of the precursors of mesoporous materials (inorganic-surfactant mesostructures). Multiple functionalization has also been done by grafting various functional groups [Eu(TTA)4] into mesoporous silicas. The adsorbed complex exhibited higher UV stability and longer excited state lifetime 2+) into mesoporous silicas from the viewpoint of the spatial distribution of [Ru(bpy)3]2+ inside the mesopore, how to control the spatial distribution and how the spatial distribution affects the performances of the resulting host–guest systems. The host–guest systems composed of [Ru(bpy)3]2+ and mesoporous silicas have been investigated for possible applications for catalyst, electrode, etc [3]2+ onto mesoporous silicas with the average pore sizes of a few nanometers was conducted from dimethylformamide solution of [Ru(bpy)3]2+ chloride [3]2+ adsorbed was controlled up to less than 1 mass% at a maximum. Dehydration of [Ru(bpy)3]2+-mesoporous silicas induced the aggregation of [Ru(bpy)3]2+ ions adsorbed, which was shown by the efficient luminescence self-quenching. The luminescence was intensified dramatically upon hydration of the samples, suggesting that the aggregated [Ru(bpy)3]2+ ions were de-aggregated to be dispersed molecularly in the mesopore. Thus, the states of the guest species are affected not only by the host–guest interactions but also by the co-adsorbed species. This is an important difference between the host–guest systems with ruthenium(II) complex cation (abbreviated as 2+-containing FSM  was used as a photocatalyst to oxidize benzene to phenol [3]2+ and mesoporous silicas using modified mesoporous silicas [3]2+) has been controlled within 0.8 μ mol m−2 mesopore surface or 1.0 mol L−1 mesopore pore volume not only by the varied loading of molecular catalyst but also by the surface density (or concentration) of immobilized functional unit (sulfonated phenyl group), which interacts with the molecular catalysts). As mentioned above, these characteristics are important to design the open space for the access and diffusion of reactants and products and the efficiency of activation (photo-excitation). (figure The adsorption of a monomer and subsequent polymerization of the monomer in the mesopore have been investigated. Poly(aniline) and poly(acrylonitrile) were synthesized in MCM-41 with the pore diameter of 2.5 nm –211. Ngu3.3.Anisotropy of the guest species included in mesoporous materials has also been a topic of interest toward three dimensionally controlled geometry of the host–guest system. This kind of research became available after the progresses of hierarchically controlled mesostructure preparation and characterization , 214–217In addition to the films, pore geometries of well-defined (and anisotropic) particles have been a topic of interest. As to the mesoporous silica spherical particles, Yano and Fukushima reported the radially arranged one-dimensional pore , which c4.Due to the ability of mesopores to accommodate various kinds of guest species, the variations in the host–guest systems are huge, which accounts for the rich materials chemistry on this topic. The structures are determined by the selection of host and guest and the interfacial design of host–guest interactions. The location of guest species varies: at the external/internal surface, inside the pore, at the entrance to the pore, and within the framework. For each possible location, the homogeneity, density and orientation of the guest species should be considered in multi-length scales. The spatial distribution  and host–guest interactions affect the diffusion and stability of the guest species, which are worth investigating further . The conPossible applications of host–guest complexes of mesoporous silicas proposed include catalyst, adsorbent, drug carrier, sensor and photonics. The spatial distribution of guest species  can be designed to initiate desired reactions in catalyst applications, to bind target species strongly in adsorbent applications, to accommodate drug molecules in drug delivery applications, to react with target molecules selectively in sensing applications, etc. Accompanied by the accommodation of functional units/guest species, the remaining nanospaces after the attachment of functional units or the inclusion of guest species should be considered geometrically, topologically and chemically for efficient diffusion of reactants and products  and adsorbates (during adsorption), for controlled up-take and release of drug (in drug delivery) and for possible molecular recognition (in sensing). In addition, the dynamic behavior of the functional units on the pore surface, which change its conformation and position to fit the resulting host–guest complexes in more stable states (induced fits), has been examined recently –235.Besides the organic compounds, inorganic nano-species such as heteropolyacids, semiconductor nanoparticles and nanocarbons have been encapsulated in the mesoporous silicas. The host–guest complexes of mesoporous and mesostructured transition metal oxides and sulfides, metals, carbons and polymers have an opportunity to which mesoporous silicas do not have access. Thus, utilizing a supramolecular templating strategy can provide a huge variety of nanostructured materials from diverse building units including both host and guest. The unlimited variations and possibilities in the construction of the host–guest systems derived from the mesoporous and mesostructured materials will be investigated for the practical applications, where precise design of the structures (both static and dynamic) of host–guest complexes are of great importance.


This paper presents an experimental study conducted to investigate the effect of fiber reinforcement on the mechanical properties and shrinkage cracking of recycled fine aggregate concrete (RFAC) with two types of fiber—polyvinyl alcohol (PVA) and nylon. A small fiber volume fraction, such as 0.05% or 0.1%, in RFAC with polyvinyl alcohol or nylon fibers was used for optimum efficiency in minimum quantity. Additionally, to make a comparative evaluation of the mechanical properties and shrinkage cracking, we examined natural fine aggregate concrete as well. The test results revealed that the addition of fibers and fine aggregates plays an important role in improving the mechanical performance of the investigated concrete specimens as well as controlling their cracking behavior. The mechanical properties such as compressive strength, splitting tensile strength, and flexural strength of fiber-reinforced RFAC were slightly better than those of non-fiber-reinforced RFAC. The shrinkage cracking behavior was examined using plat-ring-type and slab-type tests. The fiber-reinforced RFAC showed a greater reduction in the surface cracks than non-fiber-reinforced concrete. The addition of fibers at a small volume fraction in RFAC is more effective for drying shrinkage cracks than for improving mechanical performance. Concrete is the most widely used material among construction materials due to its superior strength and durability . In KoreAccording to the Ministry of Environment report in Korea, in 2012, the amount of construction waste was 186,629 tons per day, which is a significant amount that has been increasing every year. The contribution of concrete waste is the largest among all other construction wastes . The recet al. [et al. [Many researchers have attempted to ensure adequate performance for recycled aggregate construction materials ,7,8,9,10et al.  investig [et al. ,12,13,14 [et al. ,16. The et al. [et al. [et al. [Although there have been studies on recycled aggregate concrete, studies focusing on the performance improvement of fiber-reinforced recycled aggregate concrete have been very limited. Carneiro et al.  conducte [et al.  investig [et al.  studied  [et al.  investigBased on the above studies, it is clear that fiber reinforcement in recycled aggregate concrete plays an important role in improving the mechanical properties and durability as well as controlling the shrinkage cracking behavior. Nonetheless, investigations on the mechanical properties, durability, and shrinkage cracking of recycled aggregate concrete with fiber reinforcement are still very few. Furthermore, most of the studies investigated fiber-reinforced recycled aggregate concrete with a relatively large amount of fiber. However, to consider the economic efficiency of recycled aggregate concrete, it is necessary to minimize the increase in cost by using a small amount of fiber for fiber reinforcement. Therefore, the objective of the current study is to investigate experimentally the effectiveness of added fibers at small volume fractions on the mechanical properties and shrinkage cracking of recycled fine aggregate concrete (RFAC). Various characteristics of fiber-reinforced RFAC pertaining to mechanical properties and shrinkage cracking were investigated, including compressive strength, modulus of elasticity, splitting tensile strength, flexural strength, drying shrinkage, and surface cracking. The results obtained provide valuable information for enhancing the capacity of fiber-reinforced RFAC to withstand mechanical degradation and reduction in shrinkage cracking, particularly from the viewpoint of using recycled aggregate materials in the construction industry field.The physical properties of the materials used are listed in The procedure for mixing the concrete mixtures is as follows. First, the cement and coarse and fine aggregate were mixed sufficiently. Second, mixing water and superplasticizer (SP) were added to the mixtures and mixed for 1.5 min. Then, the PVA or nylon fibers were added to the concrete mixtures, and mixing was continued for 1.5 min. Finally, the fresh concrete mixtures were cast into cylindrical- and prismatic-shaped molds as well as plat-ring-type and slab-type molds. From each mixture, six 100 × 200 mm cylinders and six 100 × 100 × 400 mm prisms were prepared for the tests on mechanical properties and drying shrinkage. All the fresh concrete had similar flow properties before casting. All the specimens were demolded, being air-cured at 20 ± 3 °C and at 60% ± 5% relative humidity for 1 day and cured at 20 ± 3 °C in water for 27 days.The flowability of the fresh concrete was measured according to the ASTM C143  standardTo investigate the shrinkage cracking behavior of concrete specimens, plat-ring-type and slab-type tests were employed, as shown in In addition, the slab-type test was devised according to the ASTM C1579  standardet al. [et al. [To investigate compressive strength of concretes, three replicate samples were tested. The results of compressive strength tests are shown in et al.  and Borg [et al. . The addAdditionally, the results exhibited that the relative strength of R-0 was lower than N-0 by 10.1%; further, in cases of fiber-reinforced RFAC, the relative strength of all specimens was lower than N-0, from 8.8% up to 17.5%. Khatib  reportedFor each concrete mixture, three replicate samples were tested 28 days after casting. The mean modulus of elasticity values for concrete specimens are shown in R2 value of 0.8978 derived from the regression formula indicates a proportional relationship for the splitting tensile strength and flexural strength in the investigated concrete specimens. The results of regression analysis indicate that flexural strength increases with an increase in the splitting tensile strength.To conduct drying shrinkage tests, three replicate samples were prepared and tested at 20 ± 2 °C and 60% ± 5% relative humidity. The results of drying shrinkage tests are shown in 2.Based on the above discussion, we identified that the recycled fine aggregates with 100% replacement influenced the lower mechanical properties and higher shrinkage cracking of concrete. Additionally, it can be concluded that the addition of fibers at a small volume fraction in RFAC is more effective for reducing surface cracks than for improving mechanical performance. In the current study, the surface cracks of RFAC could be controlled by synthetic fiber reinforcement at a small volume fraction of less than 0.1%. In previous studies ,42, polyThe compressive strength of all RFAC specimens was lower than that of N-0 regardless of fiber reinforcement. This behavior can be attributed to the influence of the weak mechanical bonding between recycled aggregate and cement paste ,31,32. TThe splitting tensile strength and the flexural strength of R-0 were lower than those of N-0 specimens—26.1% and 18%, respectively. However, in cases of fiber-reinforced RFAC with a fiber volume fraction of 0.1%, the splitting tensile strength and flexural strength were similar to those of N-0. It can be inferred that fiber reinforcement of a small amount in RFAC contributed to an improvement in the interfacial bonding capacity between the cement matrix and aggregate.Regardless of the addition of fibers, the drying shrinkage of RFAC was higher than that of N-0. This result can be attributed to the influence of the higher porosity of the recycled fine aggregate ,38. ThisThe surface crack area of fiber-reinforced RFAC was significantly reduced according to increasing fiber volume fraction compared to that of N-0. These results were observed in both indoor accelerated plat-ring-type tests and long-term outdoor exposure slab-type tests. The results of R-0 in terms of cracking behavior were improved by effective reinforcement with PVA and nylon fibers. Fiber reinforcement with a small volume fraction in RFAC contributed to surface cracking resistance of concrete specimens.It was determined that the effectiveness of added fibers at a small volume fraction in RFAC with 100% fine aggregate replacement is significant for the reduction of surface cracks rather than for improvement of mechanical performance. However, to clarify the effect of fiber reinforcement with a small volume fraction for shrinkage cracking resistance, additional investigations of the influences of the variety of added fiber properties such as aspect ratio, organic or inorganic need to be addressed in future works.The objective of this study was to experimentally investigate the effectiveness of added fibers at small volume fractions on the mechanical properties and shrinkage cracking of fiber-reinforced RFAC by comparison with NFAC and non-fiber-reinforced RFAC. Based on the experimental results, the main findings of this study, which are useful in describing the mechanical performance and shrinkage cracking capacity control, are as follows:


To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics.Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class.Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites.Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest. The availability of antibiotics without a doctor’s prescription varies,,––Many studies of antibiotic use have been conducted in various health-care settingsThe MAL-ED study designSurveillance for illnesses and antibiotic use was conducted twice per week by fieldworkers at home visits until the child was two years of age or was lost to follow-up. Children were referred to locally available care, generally a local clinic, when ill.To validate mothers’ reports of antibiotic use, we randomly selected 4409 of the fieldworkers’ medical care report forms (including at least 200 records of antibiotics per site) and extracted all antibiotic information. We assessed the concordance between mother-reported antibiotic use and antibiotic use as documented on the medical care report forms.All sites received ethical approval from their respective government, local institution and collaborating institution ethical review boards. We obtained informed consent from the mother of each child.We counted distinct antibiotic courses when separated by at least two antibiotic-free days. The results were insensitive to an alternative definition using three antibiotic-free days; only 580 (3.4%) of 16 913 courses occurred within three days. The duration of antibiotic courses was defined as the total number of days on which antibiotics were received, assuming antibiotics were not received on missed surveillance days . A child was classified as exposed to high antibiotic use if he or she received more than or equal to the median number of courses received by children at his or her study site in the first two years of life.We based illness definitions on Integrated Management of Childhood Illness guidelines.Socioeconomic status was described using the child’s average score on the WAMI index based on: household access to improved water and sanitation; wealth measured by eight household assets; mother’s education; and monthly household income.We calculated the incidence of antibiotic use as the number of courses divided by the number of at-risk surveillance days. The incidence over the first two years of life was estimated using a pooled logistic regression model with a restricted quadratic splineWe adjusted for the following: study site; the proportion of days ill with diarrhoea, cough, fever, vomiting and fieldworker-confirmed acute lower respiratory infection in the first two years of life; and the interaction between this proportion and study site. To estimate the associations between overall antibiotic use and child and household characteristics we used linear regression for the proportion of days on antibiotics and log-binomial regression for risk of high antibiotic use.We then described the frequency of treatment for diarrhoea and respiratory illnesses. We estimated the associations between the characteristics of those episodes and antibiotic treatment using log-binomial regression, adjusting for study site and other episode characteristics. We also accounted for correlations between episodes in the same child using generalized estimating equations with a robust variance estimator. Among treated episodes, we used these log-binomial models to estimate the associations between antibiotic class chosen and episode and child characteristics.We included 2134 children in the MAL-ED cohort who were surveyed for antibiotic use for any illness on at least one day in the first two years of life. Over a mean of 631 days of observation per child , 16 913 courses  of antibiotics were recorded. This corresponded to an overall average antibiotic use of 4.9 courses per child per year. The median duration of antibiotic courses was 5 days (interquartile range: 3 to 7). Extended courses of antibiotics were rare; only 53 (0.3%) courses had durations longer than 1 month.The magnitude of use differed across the eight sites . FrequenEarly antibiotic use was common even in the first 6 months of life. In Dhaka and Naushahro Feroze, more than 98.0% of children followed until at least age 6 months had received antibiotics by that age . More thA total of 1741 children (81.6%) remained under surveillance until at least two years of age. More boys  than girls  received at or above the site-specific median number of antibiotic courses . AdjustiA total of 10 161 diarrhoea episodes were recorded among 1201 of the children; 4649 (45.8%) episodes were treated with antibiotics . The useMothers reported bloody stools in 499 (4.9%) diarrhoea episodes. A higher proportion of episodes of bloody diarrhoea  were treated with antibiotics than those without bloody stools  were treated with antibiotics than those in boys  were twice as likely to be treated with fluoroquinolones compared with non-bloody episodes (462/9661) . Bloody episodes were also 20 to 40% more likely to be treated with macrolides, cephalosporins and metronidazole, and were less likely to be treated with penicillins .Diarrhoea episodes among children from higher socioeconomic status were more likely than those occurring among children of lower socioeconomic status to be treated with metronidazole  and macrolides  and less likely to be treated with penicillins . The child’s sex did not affect choice of antibiotic class for diarrhoea.Of 20 685 respiratory illness episodes among 1672 children, 8992 (43.5%) episodes were treated with antibiotics. Use of antibiotics was lowest in Fortaleza (35.5% of 431 episodes) and highest in Haydom  episodes of respiratory illnesses had signs of acute lower respiratory tract illness. A higher proportion of these episodes  were treated with antibiotics than were episodes of upper respiratory illness  and cephalosporins  and correspondingly less use of penicillins . There was no association between sex and antibiotic class used for respiratory illness.Overall concordance between antibiotics reported in the medical care report forms and caregiver-reported antibiotic use was high 1737 (85.8%) of 2042 forms analysed .Box 1Medical care report forms were identified for 13 393 (79.2%) of all 16 913 antibiotic courses, and the validation sample yielded 2024 antibiotic prescriptions from 4409 forms. Concordance between use of antibiotics reported in the medical care report forms and mother-reported antibiotic use was high; on 1737 (85.8%) of forms the antibiotics corresponded with mothers’ reports on the same day. The concordance between antibiotic classes was also high: 95.1% (849/893) for penicillins, 94.8% (329/247) for cephalosporins, 86.6% (265/306) for macrolides, 85.2% (213/250) for metronidazole, 73.4% (177/241) for sulphonamides and 70.0% (42/60) for fluoroquinolones.,Despite substantial heterogeneity, the frequent and early use of antibiotics in these low-resource settings is striking. In the most extreme case, children at the site in Pakistan were exposed to antibiotics on approximately one-fifth of days in their first 6 months of life. Antibiotic usage rates were higher in most sites than that reported for children aged 3 to 24 months in the United States of America in 2010 (0.9 to 1.7 courses per child-year).,Illness symptoms were strong drivers of antibiotic treatment for both diarrhoea and respiratory illnesses, demonstrating that treatment decisions were made rationally according to illness severity. However, many episodes of non-bloody diarrhoea (44.2%) and non-acute-lower respiratory-tract illness (39.5%) were treated with antibiotics, contrary to international recommendations against routine use of antibiotics for non-bloody diarrhoeaConversely, while antibiotic treatment is recommended for dysenteryThe lower frequency of treatment among girls compared with boys after adjusting for illness burden and severity indicates that social factors also likely played a role in treatment decisions. Socioeconomic status was associated with frequency of antibiotic treatment as well as the antibiotic classes chosen for both diarrhoea and respiratory illnesses. Increased macrolides and cephalosporins use compared to less penicillins use among families with higher socioeconomic status corresponds to higher prices for these drugs, which may be a barrier to access for low-income families.This analysis provides a comprehensive description of antibiotic use across eight low-resource country settings, using data reported on every day of the first two years of life, a method which is superior to that of retrospective surveys. Using data on diarrhoea and respiratory illness symptoms, we were able to document treatment frequency and to comment on compliance with international guidelines. Mothers’ reports of antibiotic use ensured that we counted antibiotics taken (not only prescribed) and captured antibiotic use from all sources, including those that would not be included in clinic or prescription records, e.g. those from alternative health-care providers. We found high concordance between mothers’ reports and medical care report forms, as has been previously described,The study was limited by incomplete details of antibiotic use, including specific drugs given and their formulations, prophylactic versus treatment use, how and where antibiotics were obtained, and the antibiotic class for the courses classified as unknown or other. We also inferred indication for treatment by concurrent illnesses and symptoms reported, without direct reports of the cause of treatment, which limits our ability to determine conclusively the appropriateness of treatment.Overall, antibiotic use early in life was common, and we found evidence of both overuse for the treatment of non-bloody diarrhoea and upper respiratory tract illnesses, and underuse for the treatment of bloody diarrhoea and acute lower respiratory tract infection. We also found evidence for sex and class differences in access to medicines. Rational antibiotic use programmes and promotion of illness-specific treatment guidelines may have the greatest impact in South Asia, where antibiotic use was highest. Planning of intervention studies involving antibiotic treatment needs to address complex, site-specific variations in use and consider the potentially high baseline frequency of antibiotic use. Further inquiry into the consequences of this highly prevalent exposure among children will be an important contribution to our understanding of child development in low-resource settings.


Structural lightweight concrete (SLWC) has superior properties that allow the optimization of super tall structure systems for the process of design. Because of the limited supply of lightweight aggregates in Korea, the development of structural lightweight concrete without lightweight aggregates is needed. The physical and mechanical properties of specimens that were cast using normal coarse aggregates and different mixing ratios of foaming agent to evaluate the possibility of creating structural lightweight concrete were investigated. The results show that the density of SLWC decreases as the dosage of foaming agent increases up to a dosage of 0.6%, as observed by SEM. It was also observed that the foaming agent induced well separated pores, and that the size of the pores ranged from 50 to 100 μm. Based on the porosity of concrete specimens with foaming agent, compressive strength values of structural lightweight foam concrete (SLWFC) were obtained. It was also found that the estimated values from proposed equations for compressive strength and modulus of elasticity of SLWFC, and values obtained by actual measurements were in good agreement. Thus, this study confirms that new structural lightweight concrete using normal coarse aggregates and foaming agent can be developed successfully. Compared to normal and heavyweight concrete, structural lightweight concrete (SLWC) has the advantage of having a finer density . Therefo3. This compressive strength is usually obtained by adding silica fume and/or fly ash to the concrete mix besides using normal coarse and fine aggregates and superplasticizers. Point B refers to normal strength concrete and point C refers to lightweight concrete that is produced from lightweight aggregates. What is proposed in this study is that structural lightweight concrete can be produced by using coarse aggregates, whereas weight restrictions can be resolved by introducing a foaming agent to the high strength concrete mix. Point A' refers to SLWC with foaming agent and point B' is the nonstructural lightweight concrete with foaming agent. In Korea, the minimal compressive strength that can be used in structural elements is 21 MPa, and it is proposed in this study to develop structural lightweight foamed concrete with a compressive strength that is higher than the compressive strength of reinforced concrete slabs.To this end, specimens of mortar with foaming agent  were constructed to evaluate their physical and mechanical characteristics. Based on the test outcome, specimens of structural lightweight foamed concrete using coarse aggregates  were developed in accordance with the SLWFM physical characteristics. The compressive strength correlation function of lightweight foamed concrete casts with different foaming agent dosage was evaluated to obtain basic data for the development of SLWFC ,5,6.In these experiments, the compressive strength of mortar without foaming agent was set as high compressive strength. The ratios of W/B were 20%, 25% and 30%. The added dosages of foaming agent were set at 0%, 0.3%, 0.6% and 0.9% of binder weight. Also, for the sake of comparison, general mortar specimens of W/C = 60% were prepared ,8.Mortar specimens of dimension 40 mm × 40 mm × 160 mm were prepared according to KS L ISO 679 [Mortar specimens were cast in the study according to KS L ISO 679 .s is specimen weight in 1000 mL.The apparent density for structural lightweight foamed mortar was calculated according to KS F 4039  as folloIt was observed that the increase in the dosage of the foaming agent resulted in a decrease in the density of fresh SLWFM up to 0.6%. Subsequently, an increase at a dosage of 0.9% was observed. Furthermore, above a dosage of 0.60%, an increase in the foaming agent dosage did not substantiality cause any deterioration of the density due to the foam and/or foam fraction. Therefore, a foaming agent dosage of 0.6% was selected as the maximum foaming agent dosage value that can be used. Similar results were obtained with W/B ratios of 20%, 25% and 30%.pw is the density of water (g/cm3)The specimen’s apparent density under dry surface conditions was calculated according to Equations 1 and 2, and the average of three specimens was determined.This phenomenon became more pronounced with higher W/B ratio. In order to prevent the fraction or linking of the foam agent, either the W/B ratio must be decreased the viscosity of mortar must be increased. The dry surface density of specimens shows a high apparent density, because of water accumulation in the internal foam, and consequently it is recommended to apply the product in construction sites under sustained dry conditions.Based on existing studies on SLWFM, the following targets were set in this study to define the applicable mixing scope for structural purposes: (i) to determine the basic characteristics; (ii) to evaluate the relevant mixing based on the characteristics in order to assess the application feasibility; and (iii) to develop an estimated correlation function between compressive strength test outcomes of SLWFM and compressive strength of SLWFC. In this study, the concrete test objectives were developed according to KS F 2403 . Among mM is the unit volume mass of concrete (kg/m3)The apparent density measurement of SLWFC was conducted in line with KS F 2409  and was versus compressive strength.Test outcomes on compressive strength showed that the dosage of the foaming agent in the range between 0.3% and 0.6% for W/B 17% and W/B 24% was appropriate to manufacture LWFC for structural purposes.Similar to the observed reduction in the density in relation to the increase in foaming agent dosage for SLWFM in previous studies, the density reduction in SLWFC concrete was found to follow similar patterns.fck is concrete compressive strength; mc is concrete density in kg/m3.Because the increase in the foaming agent dosage results in a decrease in the stress, the modulus of elasticity decreases as well. It was found that the measured values of modulus of elasticity and compressive strength of SLWFC from this study matched the values calculated using Equations 4 and 5 suggested in concrete structural design standard explanation book .(4)fcuFm and Fc) were then calculated. The porosity (Ap) dependence on the foaming agent was also calculated in order to estimate the compressive strength of foamed agent mortar (Fam) and foamed agent concrete (Fac) of SLWFM and SLWFC.After the completion of casts of mortar and concrete specimens, compression tests were conducted, and the values of compressive strength of mortar and concrete without foaming agent  of foaming agent dosages for mortar and concrete can be calculated according to:The gradient of the straight line of both mortar and concrete can be used in Equations 6 and 7. Thus, the compressive strength (Furthermore, the effects of long term creep, SLWFC pumpability and workability, shrinkage and fire are important factors and are currently addressed in the ongoing study.The increase in the foaming agent dosage results in the development of pores and, as a result, the density of mortar and concrete decreases.In order to obtain higher compressive strength, it is essential that the matrix of the concrete should be improved. Therefore, it is judged that creating pores through foaming agent addition to ultra-high strength concrete would be more efficient to produce structural lightweight concrete.In the scope of this study, the maximum dosage of foaming agent to produce independent foams was 0.6% by binder weight and the SEM analysis verified the existence of independent foam formation with sizes of 50–100 μm.It is possible to calculate the modulus of elasticity and compressive strength of structural lightweight foamed concrete from the measured values of modules of elasticity and compressive strength of concrete without foaming agent.This study confirms that structural lightweight concrete can be made with normal coarse aggregates and foaming agent.To study the feasibility of developing structural lightweight concrete using normal coarse aggregates and foaming agent admixture, experiments were conducted on specimens to measure and estimate compressive strength of SLWFC. The following conclusions may be drawn:


While opioid abuse is an established medical and public health issue, the increased availability of highly potent synthetic opioids, such as fentanyl, has given rise to acute health complications, including a comatose state and death during drug overdose. Since respiratory depression that leads to acute hypoxia is the most dangerous complication of opioid drug use, we examined the effects of intravenous heroin and heroin contaminated with 10% fentanyl on oxygen levels in the nucleus accumbens (NAc) monitored using high-speed amperometry in freely moving rats. Additionally, we examined the effects of heroin, fentanyl, and their mixture on locomotion and temperatures in the NAc, temporal muscle, and skin. Both fentanyl and heroin at human-relevant doses  induced rapid, strong and transient decreases in NAc oxygen, indicative of brain hypoxia. When the heroin-fentanyl mixture was injected, the NAc hypoxic response was greatly potentiated in its duration, suggesting sustained hypoxia. In contrast to modest, monophasic brain temperature increases caused by heroin alone, the heroin-fentanyl mixture induced a biphasic temperature response, with a prominent postinjection decrease resulting from peripheral vasodilation. This hypothermic effect, albeit much smaller and more transient, was typical of fentanyl injected alone. Our findings indicate that accidental use of fentanyl instead of heroin, or even a relatively minor contamination of “street heroin” with fentanyl, poses great danger for acute health complications, including a comatose state and death. Respiratory depression with subsequent acute hypoxia is the leading cause of lethality induced by intravenous heroin at high doses. This effect may be enhanced when the heroin consumed is contaminated with fentanyl, a much more potent opioid drug. By using high-speed amperometry with oxygen sensors in freely-moving rats, we show that both fentanyl and heroin at human-relevant doses induce rapid, strong but transient decreases in NAc extracellular oxygen levels. This brain hypoxic effect was greatly enhanced when rats received a heroin dose laced with 10% of fentanyl. Our findings indicate that the accidental use of fentanyl instead of heroin, or even a relatively minor contamination of “street heroin” with fentanyl, poses great risk for acute health complications, including a comatose state and death.“Street heroin” may often be contaminated with fentanyl, a synthetic opioid drug 20–40× as potent as heroin . Due to In this study, we examined the effects of heroin contaminated with fentanyl on brain oxygen levels directly assessed by high-speed amperometry with Pt-Ir oxygen sensors. This technology, recently developed in our lab, allows for the direct evaluation of rapid fluctuations in brain oxygen levels, a critical homeostatic parameter inaccessible before the advent of such technology. Our experimental paradigm allows us to monitor brain oxygen levels following stress- and cue-free intravenous drug injections in awake, freely moving rats and determine the effects of drugs of abuse in the absence of confounding variables such as anesthesia. Using this novel technology, we recently examined physiological fluctuations in brain oxygen levels and established their relationships with metabolic neural activation and local vascular response . We alsoOur oxygen recordings were supplemented by monitoring temperature in the brain, temporal muscle, and skin. While brain temperature by itself is an important homeostatic parameter, the three-point temperature recording paradigm used in this study allowed us to determine the basic physiological mechanisms underlying drug-induced brain temperature responses: changes in intrabrain heat production due to metabolic brain activation/inhibition and changes in heat loss/retention due to changes in skin vascular tone . These dHere, we sought to mirror a real-world scenario in which an individual who believes he or she is consuming a standard dose of heroin is actually consuming a heroin sample laced with a smaller amount of fentanyl. We compared the effects of a control dose of heroin (400 μg/kg) and this dose contaminated with 10% fentanyl, which gives rise to a heroin-fentanyl mixture containing 360 μg/kg of heroin and 40 μg/kg of fentanyl. Both 400 μg/kg of heroin and 40 μg/kg of fentanyl are much lower than the LD50 assessed in rats [15–20 mg/kg ; 1–3 mg/A total of 25 male Long-Evans rats (Charles River Laboratories) weighing 460 ± 40 g at the time of surgery were used in this study. Rats were individually housed in a climate-controlled animal colony maintained on a 12/12 h light/dark cycle (lights on at 6 A.M.) with food and water freely available. All procedures were approved by the National Institute on Drug Abuse Intramural Research Program (NIDA-IRP) Animal Care and Use Committee and complied with the Guide for the Care and Use of Laboratory Animals . Maximal care was taken to minimize the number of experimental animals and avoid any possible discomfort at all stages of the study.n = 12 rats), we examined the effects of iv fentanyl (40 μg/kg), heroin (400 μg/kg), and their mixture (360 μg/kg heroin + 40 μg/kg fentanyl) on temperatures in the NAc, temporal muscle, and skin as well as locomotor activity. In the second, electrochemical experiment (n = 13 rats), we examined the effects of fentanyl (40 μg/kg), heroin (400 μg/kg), and their mixture (360 μg/kg heroin + 40 μg/kg fentanyl) on extracellular levels of oxygen in the NAc.This study describes the results of two experiments conducted in awake, freely-moving rats. In the first, thermorecording experiment  and recorded at 1-s intervals, using the PAL 8100: Biosensors legacy software .For direct assessment of fentanyl-induced changes in brain oxygen, we used commercially produced oxygen sensors . Each sensor consists of an epoxy-sheathed disk electrode that is grounded to a fine surface using a diamond-lapping disk. The sensors are prepared from Pt-Ir wire 180 μm in diameter, with a sensing area of 0.025 mmOxygen sensors were calibrated at 37°C by the manufacturer (Pinnacle Technology) according to a standard protocol described elsewhere . The senThese sensors were previously used for assessment of physiological fluctuations in NAc oxygen ; this puTemperature recordings were conducted during three 6- to 8-h sessions, during which the rats received single iv injections of fentanyl , heroin , and a freshly prepared mixture of heroin and fentanyl . All drug injections were conducted ∼2 h after the session start while the rats were under quiet resting conditions and temperatures had stabilized at their basal levels. Recordings continued for at least 4 h after drug injections. Each treatment session was followed by one drug-free day. Injections of heroin and the heroin-fentanyl mixture were counterbalanced.Electrochemical recordings were performed in two groups of rats, which underwent ∼2 h of habituation to the recording environment. In the first group, the rats received a single injection of fentanyl (40 μg/kg). In the second group, recordings were conducted during two sessions (with one drug-free day in between) and each rat received both heroin (400 μg/kg) and a heroin-fentanyl mixture . The order of drug presentation was counterbalanced. At the beginning of each session, rats were minimally anesthetized (<2 min) with isoflurane and the sensor was inserted into the NAc. The rat was placed in the testing chamber and the sensor was connected to the potentiostat via an electrically shielded flexible cable and a multichannel electrical swivel. The injection port of the jugular catheter on the head mount was connected to a plastic catheter extension, which allows stress- and cue-free drug delivery from outside the cage. Testing began ∼120 min after insertion of the sensor, when baseline currents had stabilized.At the end of experimentation, rats were deeply anesthetized with Equithesin  and isoflurane and decapitated. Then, the brain was removed, stored in 10% formalin, and sectioned for verification of sensor placements using a rat stereotaxic atlas ; the brapost hoc tests.Temperatures were sampled at 10-s time bins and later analyzed at two time resolutions  to determine drug-induced changes in absolute temperature in each recording location, relative temperature, and NAc-muscle and skin-muscle temperature differentials (a difference between relative temperature changes in the corresponding locations). As described in our previous studies . One-way and two-way repeated measure ANOVAs (followed by Fisher PLSD post hoc tests) were used to evaluate the statistical significance of drug-induced changes in oxygen levels. We also used time-dependent correlation analyses to examine the relationships between oxygen, brain temperature, and temperature differentials.Electrochemical data were sampled at 1 Hz  using the PAL software utility  and analyzed with two time resolutions . Electrochemical data were first analyzed as raw currents. Because each of the individual sensors differed slightly in background current and substrate sensitivity Data presented in this report were obtained in rats with artifact-free neurochemical and temperature recordings. In each rat, the locations of brain sensors were histologically verified to be located within the NAc shell.F = 3.82, p < 0.001; Fentanyl injected at a 40 μg/kg dose rapidly and strongly decreased NAc oxygen levels  = 7.8, 10.6, and 6.7 for NAc, muscle, and skin temperatures, respectively; p < 0.0001; F = 4.3, p < 0.0001). The skin-muscle differential, a measure of skin vascular tone, initially increased slightly but then decreased more strongly  = 2.9, p < 0.0001). Together, these data indicate that fentanyl at a 40 μg/kg dose causes initial hypothermia due to transient skin vasodilation and heat loss to the external environment, followed by hyperthermia mediated by metabolic brain activation and resultant intrabrain heat production as well as heat retention due to skin vasoconstriction. Fentanyl at this dose decreased locomotor activity and resulted in near-total freezing for 70–80 min postinjection.Fentanyl induced a biphasic temperature response, with an initial decrease followed by an increase  = 6.33, p < 0.001; Similar to fentanyl, heroin injected at a 400 μg/kg dose significantly decreased NAc oxygen levels  = 8.8, 10.3, and 7.3, respectively; p < 0.0001; F = 1.9, p < 0.001). This effect was relatively transient, delayed, and evident within 15–60 min postinjection. Due to weaker increases in skin temperature, the skin-muscle differential monophasically decreased for ∼150 min postinjection  = 4.0, p < 0.001). Heroin induced near-total locomotor inhibition for the first 60 min after injection, after which locomotion was slightly elevated above the preinjection baseline.In contrast to fentanyl, heroin monophasically increased temperature in the NAc, muscle, and skin  = 11.6, p < 0.001; t = 6.69, p < 0.001) and 5.5-fold larger than for heroin alone  = 4.89) with significant between-group differences from 7.5 to 47.5 min postinjection.Similar to fentanyl and heroin injected alone, an opioid mixture containing 360 μg/kg of heroin and 40 μg/kg of fentanyl induced a robust decrease in NAc oxygen levels  = 19.2, 21.4, and 20.8 for NAc, muscle, and skin temperatures, respectively; F = 0.2, p > 0.05). The skin-muscle differentials showed biphasic dynamics, with the initial increase followed by a more prolonged and larger decrease. Together, these data indicate that a heroin-fentanyl mixture causes initial hypothermia due to vasodilation and heat loss to the environment, which is followed by robust hyperthermia resulting from intrabrain heat production due to metabolic brain activation. The heroin-fentanyl mixture caused near-total locomotor inhibition from ∼20 to 120 min postinjection, after which locomotor activity increased before returning to its pre-injection baseline ∼200 min postinjection.In contrast to pure heroin, the opioid mixture induced a biphasic temperature response evident in all recording locations .Since the drug-induced changes in temperature and oxygen were rapid, we also examined the dynamics of these changes with high temporal resolution for the first 20 min postinjection . In this case, temperature remained stable when oxygen dropped but the return of oxygen to baseline was related to decreases in temperature below baseline. A similar negative correlation was found for oxygen and the brain-muscle differential during the period of oxygen response . Despite much more prolonged hypoxia, the relationship between oxygen and the brain-muscle differential after injection of the heroin-fentanyl mixture was similar to that seen with fentanyl alone.More complex relationships were found with the heroin-fentanyl mixture, which induced a much longer decrease in NAc oxygen  decreased oxygen concentrations to 30–40% of baseline, suggesting robust hypoxia. Importantly, these effects were very rapid, appearing during or immediately after the injection and reaching nadir within 100–200 s from the injection onset. For both drugs, oxygen levels recovered relatively quickly, returning to baseline 10–20 min after the injection. However, the fentanyl-induced oxygen drop was more rapid and transient than that for heroin. These between-drug differences in the dynamics of oxygen response could be related to the known differences in pharmacokinetics. While both drugs easily cross the blood-brain barrier and interact with the same μ-opioid receptors, fentanyl directly acts on these receptors, whereas heroin acts as a prodrug, with two pharmacologically active metabolites, 6-MAM and morphine, which display different pharmacokinetics .Both fentanyl and heroin at a 1:10 dose ratio strongly inhibited locomotor activity with similar durations, but they differed in temperature responses. Both drugs induced modest hyperthermia, but this response for fentanyl was preceded by a temperature decrease evident within the first 30–40 min after the injection. Both drugs also increased NAc-muscle differentials, indicating increased intrabrain heat production as a consequence of metabolic brain activation. This effect, however, was delayed, transient, and stronger for fentanyl than for heroin. Our correlative analysis confirmed that the oxygen drop induced by either fentanyl or heroin is not related to metabolic brain activation, which instead could be an adaptive response caused by hypoxia. Both drugs induced skin vasoconstriction; this effect was the most prolonged of the parameters considered and it could be responsible for the tonic increases in brain temperature induced by each drug. In contrast to heroin, fentanyl initially induced a transient increase in the skin-muscle differential, implying skin vasodilation, which appears to be responsible for the initial decrease in brain temperature seen with this drug.Several important differences in oxygen response were found when rats were injected with heroin with 10% addition of fentanyl. First, the NAc oxygen decrease was greatly potentiated. Although the mean magnitude of oxygen decrease did not differ statistically from heroin alone, in half of the rats the heroin-fentanyl mixture induced decreases lower than 25% of the baseline, suggesting robust hypoxia. Similar decreases were seen only in a quarter of the cases with pure heroin. However, the duration of hypoxia drastically increased after receiving the drug mixture. This change is best represented by the area under the curve, which was over five times larger than that for pure heroin. This prolongation of brain hypoxia is functionally important because brain cells may tolerate transient decreases in oxygen inflow, but are damaged to a greater extent when hypoxia is more prolonged .https://www.erowid.org/).The heroin-fentanyl mixture also induced a distinct temperature response. In contrast to the slow and gradual hyperthermic effect seen with pure heroin, the heroin-fentanyl mixture induced a biphasic brain temperature response, with a prominent decrease for ∼80 min postinjection. This decrease was coupled with an increase in the skin-muscle differential, suggesting skin vasodilation and enhanced heat dissipation as a primary factor determining the decrease in brain and muscle temperatures. Although temperature then increased and its increase was larger than that of heroin alone, the immediate hypothermic effect of the heroin-fentanyl mixture is the most clinically relevant because most acute complications related to fentanyl occur within the first 20 min after its intravenous injection (The brain is one of the heaviest consumers of oxygen in the body and accounts for ∼20% of total oxygen consumption . High meOur correlative analysis confirmed that the oxygen decreases induced by opioid drugs occurred before any increases in brain temperature and brain-muscle differentials , parametDirect, high-speed evaluation of NAc oxygen dynamics revealed that iv fentanyl, heroin and their mixture induce robust brain hypoxia. Importantly, this effect is remarkably rapid, reaching its maximum at 1.5–4.0 min after the injection onset. While changes in oxygen occurring in humans could have slightly slower dynamics than in rats, the exceptionally rapid time course of the brain hypoxic response poses significant constraints on using opioid antagonists such as naloxone to treat this dangerous condition. While naloxone is highly effective in blocking most effects of opioid drugs, to be effective it should be delivered within a critical time window following opioid administration. This issue could be less important for subcutaneous injections or oral ingestion of these drugs since these routes of drug delivery possess much slower drug pharmacokinetics and a longer time window for possible treatment.As shown in this study, even minor contamination of heroin with fentanyl results in strong potentiation of brain hypoxia. In contrast to the relatively transient brain oxygen decreases seen with fentanyl and heroin alone, the hypoxic response became sustained with the heroin-fentanyl mixture, persisting for up to 2 h after drug administration. In addition, the heroin-fentanyl mixture prolonged motor inhibition and strongly decreased brain and body temperature for ∼1 h due to initial vasodilation. This response pattern, suggesting deep sedation, is typical for general anesthesia  and coul