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A miniature ionization vacuum sensor (IVS) based on an on-chip SiOx-based tunneling electron source is reported. The vacuum sensor fabricated by microfabrication technologies exhibits a compact multilayered structure with overall dimensions of $13\times 9\times2.7$ mm3, where the electron source chip, Si layer of the electron collector, Si layer of the ion collector, and glass spacers between them are stacked together by an anodic bonding method. Electron impact ionization occurs in a semiclosed cavity through the electron and ion collector layers and glass spacers. Because of the compact structure, low working voltage of SiOx-based tunneling electron sources, and stable electron emission of the electron sources in a poor vacuum, a wide linear detection range from $1.3\times 10^{-2}$ to 133 Pa and a sensitivity of $8.3\times 10^{-4}$ Pa−1 have been demonstrated for the devices. These advantages, including miniature size, a detection range up to the rough vacuum regime, and the capability of batch fabrication with microfabrication technologies, make our IVSs promising in vacuum measurements.

In this study, micro-grooves were fabricated on a chemical vapour deposition (CVD) diamond coating using spray-mist-assisted laser machining. In this paper, the advantages and characteristics of spray-mist-assisted laser machining are analysed through comparison with other forms of laser machining based on morphology and composition. Meanwhile, the effects of process parameters (laser power, scanning speed, defocusing quantity, air pressure, spray angle, and offset distance) on the machining characteristics were investigated using the Taguchi method, and the optimal parameter range of spray-mist-assisted laser-machined CVD diamond coating was obtained. The results indicate that spray-mist-assisted laser machining can effectively remove the recast layer and ensure the precision and continuity of laser machining. The most significant factor affecting the cross-sectional area of the grooves is laser power, while laser power and scanning speed significantly affect depth-to-width (D/W) ratio of grooves. The spray parameters had no significant effect on the characteristics of ablative grooves because the thickness of the water film formed by spray-wall impingement was relatively thin and stabilised.

Huang Y, Liu W, Gao F, Fang X, Chen Y. Int J Nanomedicine. 2016;11:1629–1641. The Editor and Publisher of the International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of an image in Figure 8B with the same image from Figure 10 in Chen et al, 2015 ‘The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment’ (https://doi.org/10.2147/IJN.S79045). Figure 8B, Heart, Saline appears to have been duplicated with the same image from Figure 10, Heart, F127/P105/MTX in Chen et al, 2015. The authors responded to our queries and explained that the animal experimental work for both studies was performed at the same time. It was possible an error was made during the arrangement of the H&E images for the respective figures from both articles. However, given the length of time that has passed since the completion of these studies the authors were no longer able to retrieve the original data. To help maintain the integrity of the scientific record the authors agreed with the decision to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

In this research, a strategy to design structured grinding wheels to machine designed structured surfaces in micro-scale through the grinding process is investigated. Firstly, the geometry of the microstructured surface is defined. A mathematical model to describe the geometry of the structured grinding wheel and the grinding parameters is presented according to the geometry of the designed microstructures on the workpiece surface. And then, several operating conditions for the grinding operation are mathematically determined and kinematically simulated using a proper programming language to produce the designed geometry of the microstructured surface. The errors in the simulated geometries of the machined microstructures are calculated and analyzed. Finally, the reasons for deviation and ability to minimize error sources are investigated.

Accurate testing and evaluation of the hydraulic performance of pressure‐compensating (PC) emitters are basic for proper operation of drip irrigation systems. However, the impacts of environmental conditions and system operation usually result in unstable water temperature. Quantifying the effects of water temperature on flow rate and hydraulic performance are of vital importance to PC emitters. In this paper, six types of widely used PC emitters were used for laboratory testing, and their flow rates in the water temperature range of 15–45 °C were measured. The results showed that both the PC emitters' flow rate and temperature discharge ratio (TDR) decreased significantly with increase of water temperature (p < 0.05), with average decreasing rates of 7.52 and 7.32%, respectively. Meanwhile, the flow coefficient (kd) showed a downward trend with higher water temperature (p < 0.05, 12.0% in average), but the effects on the flow index (x) of the PC emitter could be ignored. This may be due to the decrease in hardness of the elastic diaphragm caused by higher water temperature, the research would provide theoretical references for correcting the performance deviation of pressure‐compensating emitters caused by temperature variation.

Thermionic electron sources are scaled down to the microscale on a chip and batch fabricated on 4-in silicon wafers by utilizing microfabrication technologies and exploiting carbon nanotubes as microscopic filaments of thermionic electron emission. The microfabricated on-chip thermionic electron sources not only satisfy the metrics of compactness and ease of batch fabrication, but also exhibit the advantages of good performance reproducibility (±6.9% variation over 100 test cycles under a driven voltage of 3.5 V) and high emission stability (fluctuation < 5% for emission current level of ≈10−8 A over 900 s) under a relatively low vacuum condition (10−4–10−2 Pa). Furthermore, to extract electrons and tune emission current, an extraction gate with a mesh is monolithically integrated with the thermionic electron sources using anodic bonding technique. The integrated electron sources exhibit a strong gate controllability and a considerable electron transmission ratio of ≈76% through the extraction gate. All these results make our devices a promising type of on-chip electron source in the applications of miniature vacuum electronic devices/systems.

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 µmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDV-gemcitabine inhibiting the metastasis of the planted tumor towards lung.

Solid solution powders of Ti-22Al-25Nb (at.%) were successfully prepared with Ti, Al, and Nb elemental powders via mechanical alloying (MA). The effects of milling time, stearic acid process control agent and Al2O3 reinforced particles on the morphology evolution, average particle size, crystallite size, solid solution and phase of mixed powders were studied. The solid solution mechanism and strengthening mechanism of Ti, Al and Nb mixed powders during MA were revealed. In addition, the strengthening effect of Al2O3 reinforced particles was clarified. The mixed powders at different milling times were characterized by X-ray diffraction and scanning electron microscopy. The microhardness of the solid solution powders was investigated, and the solid solubility of Al and Nb atoms in the Ti matrix was quantitatively calculated. The results revealed that the crystallite size of mixed powders without the addition of Al2O3 reinforced particles decreased with the increase of MA time, and was 18 nm after MA for 60 h. The solid solubility values of Al and Nb in the Ti matrix were 22.68 at.% and 9.49 at.%, respectively. The addition of Al2O3 reinforced particles could effectively refine the mixed powder particles, but had no obvious effect on the evolution of particle morphology; the values of load-bearing effects ( Δ σ Load ) and orowan strengthening ( Δ σ Orowan ) were determined to be 27.5 MPa and 88.4 MPa, respectively. The microhardness values of the Ti-22Al-25Nb solid solution powders and Ti2AlNb-5 wt% Al2O3 nanocomposite powders were 435 HV and 465.8 HV, respectively. Compared to Al2O3 reinforced particles, stearic acid process control agent could significantly inhibit the welding between Ti, Al and Nb powders, making the powders more prone to disperse and break into small flakes with a smaller average particle size of 10 µm at 60 h. With the addition of stearic acid, the mechanical alloying process of Ti, Al and Nb element powders was inhibited, and the solid solubility of Al in the Ti matrix and the microhardness of the mixed powders after MA for 60 h were reduced to 16.31 at.% and 330 HV, respectively.

In order to meet the needs of the development of low-rise assembly structure in rural areas, a fabricated light-weight steel frame-composite light wall structure is proposed in this paper. The light-weight steel frames are used to bear the vertical loads. The single-row-reinforced recycled concrete wall-boards are used as lateral members to resist most of the horizontal earthquake loads. The wall-board, EPS (Expanded Polystyrene) insulation modules,and fly ash blocks form the thermally insulated wall. Four fabricated lightweight steel frame-composite light wall structures and one light-weight steel frame(FRA)structure were tested under the low cyclic loads. The influence of wall reinforcement spacing and structural form (be it fly ash block or not) on the seismic performance of this new structure was analysed and the damage process of the specimen was simulated using the ABAQUS®software. The results show that the light steel frames and the single-row-reinforced recycled concrete wall-board can work well together. Furthermore, the structure has two clear seismic lines. Due to the use of EPS insulation modules and fly ash blocks, thestructure has good anti-seismic and thermal insulation abilities. Reducing the spacing of bars or compositing fly ash blocks can significantly improve the seismic performance of the structure. The finite element method (FEM) calculations agreed well with the experimental results, which validates the proposed model

Wenchao Liu1,2, Yujia Mao1,2, Xiaoyi Zhang1,2, Yaonan Wang1,2, Jianhui Wu1,2, Shurui Zhao1,2, Shiqi Peng1,2, Ming Zhao1–3 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 3Department of Biomaterials, Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Beijing University of Chemical Technology, Beijing 100026, People’s Republic of ChinaCorrespondence: Ming ZhaoBeijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, No. 10, Youanmenwaixitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 108 391 1535Email mingzhao@bjmu.edu.cnBackground: Gemcitabine has been widely used as a chemotherapeutic drug. However, drug resistance, short half-life and side effects seriously decrease its chemotherapeutic efficacy.Purpose: The object of preparing RGDV-gemcitabine was to prolong the half-life, to overcome drug resistance and to eliminate bone marrow toxicity of gemcitabine.Methods: Arg-Gly-Asp-Val was coupled with gemcitabine, forming 4-(Arg-Gly-Asp-Val-amino)-1-[3,3-difluoro-4-hydroxy-5-(hydroxylmethyl)oxo-lan-2-yl]pyrimidin-2-one (RGDV-gemcitabine) involving 9-step reactions. The advantages of RGDV-gemcitabine to gemcitabine were demonstrated by a series of assays, such as in vitro half-life assay, in vitro drug resistance assay, in vivo anti-tumor assay, in vivo kidney toxicity assay, in vivo liver toxicity assay and in vivo marrow toxicity assay. The nano-features of RGDV-gemcitabine were visualized by TEM, SEM and AFM images. The tumor-targeting action and release of RGDV-gemcitabine were evidenced by FT-MS spectra.Results: Half-life and anti-tumor activity of RGDV-gemcitabine were 17-fold longer and 10-fold higher than that of gemcitabine, respectively. RGDV-gemcitabine, but not gemcitabine, showed no kidney toxicity, no liver toxicity, no marrow toxicity and no drug resistance. The advantages attributed to the nanofeatures of RGDV-gemcitabine were targeting tumor tissue and releasing gemcitabine in tumor tissue.Conclusion: RGDV-gemcitabine successively overcame the defects of gemcitabine and provided a practical strategy of nano-medicine.Keywords: gemcitabine, modification, half-life, anti-tumor, tumor targeting, release, toxicity, nano-species

A stimulation technology of multi-stage fractured horizontal well is commonly used for enhancing the productivity in the development of low-permeable oil reservoirs. However, it is well known that the fluid flow in low-permeable oil reservoirs doesn't obey conventional Darcy's law, and the threshold pressure gradient exists; as a result, in fact, the model of multi-stage fractured horizontal well in low-permeable oil reservoirs belongs to a nonlinear moving boundary problem. And realization of the numerical simulation for the model is very complicated and difficult. It is significant to figure out the threshold pressure gradient effect on the numerical simulation results for the solution of actual engineering problems. In view of the concerns, based on the subsurface Darcy's flow module in COMSOL Multiphysics, an effective numerical simulation method is presented here: The non-Darcy kinematic equation at the full pressure gradient range is expressed at the interface of the gravitational acceleration vector in Darcy's law. Furthermore, the simulation method is strictly verified through the comparison with two analytical solutions for a one-dimensional case and a two-dimensional case (radial flow) respectively. Consequently, according to a constructed model, which can cover non-Darcy flow in the unstimulated reservoir area with threshold pressure gradient, Darcy's flow in the stimulated reservoir area and Darcy's flow in the main hydraulic fractures, the two-dimensional numerical simulation of the multi-stage fractured horizontal well in the low-permeable oil reservoir is realized just through the subsurface Darcy's flow module. Finally, through analyses and discussions on the numerical results for several designed simulation scenarios, some significant conclusions are obtained such as due to the threshold pressure gradient effect, there exists large undeveloped areas in low-permeable oil reservoirs, which don't change with the production time for the constant well production pressure condition; SRV fracturing can largely improve the utilization degree of the low-permeable reservoir area between the adjacent main hydraulic fractures at the early production period; it is very necessary to incorporate the threshold pressure gradient effect in the simulation for the optimal well spacing design in the development of low-permeable oil reservoirs.

Many engineering technologies involve the moving boundary problems for the radial seepage flow with a threshold pressure gradient, such as the well testing in the development of low-permeability reservoirs, heavy oil reservoirs and groundwater resources. However, as a result of the strong nonlinearity, an exact analytical solution of the moving boundary problems for the radial seepage flow with a threshold pressure gradient has not been obtained yet. Here, a dimensionless moving boundary mathematical model for the radial fluid flow in an infinite low-permeability reservoir with a threshold pressure gradient is developed first. The setting of a variable well production rate for an inner boundary condition can make the mathematical model exhibit a full self-similarity property. Second, by introducing some similarity transformations, the nonlinear system of PDEs of the model can be equivalently transformed into a closed pseudo-linear system of ODEs, whose exact analytical solution can be easily obtained. What's more, the existence and the uniqueness of the exact analytical solution to the moving boundary model are also proved strictly through the mathematical analysis. Third, it is also strictly proved that the exact analytical solution can be degenerated to that of the model of the Darcy's radial fluid flow as the threshold pressure gradient approaches to zero. Finally, by a comparison of model analytical solutions, it is demonstrated that the moving boundary conditions must be incorporated in the modeling of the radial seepage flow with a threshold pressure gradient; otherwise, the effect of the threshold pressure gradient on the radial seepage flow can be overestimated largely.

GNSS based Bistatic Forward Looking Synthetic Aperture Radar (GNSS-BFLSAR) system is particular kind of passive bistatic SAR system. In the system, GNSS is used as the transmitter, while the receiver is mounted on the airplane. The airplane travels along a straight line and the imaging target is in the front. GNSS-BFLSAR is benefited from low cost and good safety. It is widely used in self-landing, self-navigating and battle field information acquiring, etc. This paper is focusing on the investigation of point target 2-D spectrum of GNSS-BFLSAR and Point Spread Function (PSF) generation method. First, a geometric model of such system is built, followed by the generation of echo signal. Then, the analytical formula of 2-D spectrum is obtained. Next, the PSF generation is provided. In the end, the whole procedure is simulated with Matlab. The simulation result verifies the validity of theoretical analysis of this paper and makes a foundation for imaging formation research of such system in the future.

In order to meet the needs of the development of low-rise assembly structure in rural areas, a fabricated light-weight steel frame-composite light wall structure is proposed in this paper. The light-weight steel frames are used to bear the vertical loads. The single-row-reinforced recycled concrete wall-boards are used as lateral members to resist most of the horizontal earthquake loads. The wall-board, EPS (Expanded Polystyrene) insulation modules, and fly ash blocks form the thermally insulated wall. Four fabricated lightweight steel frame-composite light wall structures and one light-weight steel frame (FRA) structure were tested under the low cyclic loads. The influence of wall reinforcement spacing and structural form (be it fly ash block or not) on the seismic performance of this new structure was analysed and the damage process of the specimen was simulated using the ABAQUS® software. The results show that the light steel frames and the single-row-reinforced recycled concrete wall-board can work well together. Furthermore, the structure has two clear seismic lines. Due to the use of EPS insulation modules and fly ash blocks, the structure has good anti-seismic and thermal insulation abilities. Reducing the spacing of bars or compositing fly ash blocks can significantly improve the seismic performance of the structure. The finite element method (FEM) calculations agreed well with the experimental results, which validates the proposed model.

A powder metallurgy (P/M) Ti-22Al-25Nb (at%) alloy was prepared by spark plasma sintering of pre-alloyed powders at 1000 °C/80 MPa/10 min. The solution treatments of the P/M Ti-22Al-25Nb alloy were conducted at a temperature range of 940–1030 °C at 30 °C intervals and holding times of 10 min, 30 min, 60 min, and 120 min. The effects of the solution temperature and the holding time on the microstructure evolution, B2 grain growth behavior, phase transition, tensile mechanical properties, and fracture behavior of the P/M Ti-22Al-25Nb alloy were systematically evaluated using optical microscopy (OM), scanning electron microscopy (SEM), X-ray diffraction, and tensile tests. The results indicated that the microstructure and mechanical properties were closely linked to the solution temperature and the holding time. The effect of the holding time and the solution temperature on the B2 grain growth is well described by Beck's equation and Hillert's equation, respectively. The tensile tests showed that the tensile properties of the solution-treated P/M Ti-22Al-25Nb alloy were mainly affected by the number of O phases in the interior of the B2 grains and the phase transition degree of the α2 phase at the grain boundary. The P/M Ti-22Al-25Nb alloy solution-treated at 940 °C/10 min exhibited the best mechanical properties at room temperature with a yield strength, tensile strength, and elongation of 867.8 MPa, 949.5 MPa, and 7.4%, respectively. A phase transition model of the α2 phase was established. In addition, a tensile fracture model of the P/M Ti-22Al-25Nb alloy solution-treated under different conditions was established.

Grain growth behavior of a powder metallurgy (P/M) Ti-22Al-25Nb alloy was investigated by applying a series of isothermal treatment tests over a wide range of temperatures and holding times. An isothermal treatment scheme was conducted in the B2 phase region (1070-1110 °C) and α2 + B2 phase region (1010-1050 °C) at holding times of 10, 30 min, 1, 2, and 3 h, respectively. The effects of temperature and holding time on the microstructure evolution and microhardness of the P/M Ti-22Al-25Nb alloy at elevated temperatures were evaluated using optical microscope, scanning electron microscope, x-ray diffraction, and Vickers hardness test techniques. The results revealed that the alloy’s treated microstructure was closely linked to temperature and holding time, respectively. The change law of B2 grain growth with holding time and temperature can be well interpreted by the Beck equation and Hillert equation, respectively. The B2 grain growth exponent n and activation energy Q were acquired based on experimental data in the α2 + B2 and B2 phase regions. In addition, the grain growth contour map for the P/M Ti-22Al-25Nb alloy was constructed to depict variations in B2 grain size based on holding time and temperature.

Traditional polar navigation usually uses grid navigation to implement great circle,which could cause problems that different grid direction of great circle makes against navigation control and great circle is not straight lines on the polar projection lead to principle error.To solve these problems, considering the idea that it is easier to navigaition control and plotting if the rumble route in the lower latitudes is straight lines on the mercator projection, a rumble route called grid rumble route which are straight lines on polar stereographic projection is suggested.Firstly, polar stereographic projection based on double projection and grid navigation are studied.Then the definition of grid rumble route and route equation is presented.Finally, compitational method of distance and grid direction for grid rumble route is provided.From the theoretical analysis and simulations, grid rumble route is approximate to great circle and great ellipse routes,the navigation distance is relatively short; thus, they are straight lines on the polar stereographic projection and grid direction is equal everywhere. Moreover, they can be used in conjunction with grid navigation method and polar stereographic projection, more applicable for the polar navigation.

In the present study, repetitive upsetting-extrusion (RUE) process was employed to induce severe plastic deformation (SPD) for an AZ91D magnesium alloy at temperatures ranging from 285 °C to 380 °C. Finite element method (FEM) and technical experiment were performed to reveal the non-uniform behavior during the RUE process. The results from the finite element analysis showed that effective strain was unevenly distributed in one-cycle strained sample and the non-uniformity would exist permanently with increasing deformation cycles. The microstructure evolution of the RUE processed alloys was characterized by optical microscopy, which clarified the microstructural development from heterogeneous and coarse as-cast structure, heterogeneous and refined structure to final homogeneous and fine-grained structure of the 340 °C and eight-cycle processed sample. In addition, a critical strain was suggested from the metallographic observation results. It was proposed that α -Mg grain structure was sufficiently refined by imposing accumulated strain beyond the critical value and the invariability of grain sizes was illustrated. A homogeneous structure with mean grain size of ∼3.04 μm was obtained after 285 °C and three-cycle RUE process, corresponding to an accumulated true strain of about 3.75. Furthermore, the fragmentation and dispersed distribution of the β -Mg 17 Al 12 phase induced by shearing was confirmed by referring to scanning electron microscope (SEM) examination. Moreover, refining mechanisms responsible for grain structure were discussed in detail with reference to the transmission electron microscope (TEM) analysis results.

Mesophase carbon microbeads (MCMBs) were synthesized by thermal polycondensation with fluidized catalytic cracking residue oil (FRO) as the feedstock. The evolution features of functional groups of the residual oils and the residual solid products from thermal polymerization were analyzed, and the effect of olefinic compounds on the coalescence between mesophase spheres was investigated in depth. The results showed that the olefin contents of residual oil, heptane-soluble, and heptane-insoluble/toluene-soluble decreased simultaneously as the reaction proceeded while that of toluene-insoluble increased, indicating that the olefins in the solvent phase could not only provide molecule sources for the development of carbonaceous mesophase but also directly assemble into the insoluble mesogens. More importantly, the involvement of olefins caused a sharp increase of the system viscosity, making it difficult for the mesophase spheres to completely coalesce into regular large ones after cohering, leading to the apparent deformation. In contrast, catalytic hydrotreatment can saturate olefinic species and enhance the hydrogen transfer ability of FRO to further avoid the induction effect of olefins, slow down the mesophase development, reduce the system viscosity, and consequently avoid the deformation of mesophase spheres.

LiNi0.8Co0.1Mn0.1O2 (NCM811) often suffers from the poor cycle stability as the cathode material for the lithium-ion battery (LIB), while Al2O3 or MgO coating is the most common method to resolve such problem. However, the reported techniques often produced Al2O3 or MgO particles with the large size or zero dimensional (0 D) spheres, which resulted in ununiform or thick layer coating on the surface of NCM811. Herein, Mg-Al layered double oxide (Mg-Al-LDO) nanosheets derived from Mg-Al layered double hydroxide (Mg-Al-LDH) were firstly studied as a potential coating material because of their two dimensions (2D) and few-layer structures (less than 10 nm). The Mg-Al-LDO nanosheets were coated on NCM811 microspheres via the intercalation-exfoliation-calcination strategy. The Mg-Al-LDO nanosheets modified NCM811 samples exhibited enhanced cycle performances. The capacity retention improvements of this work (11–18%) were higher than those of the reports (0.7–15.6%). Typical sample showed the capacity retention of 95.5% after 50 cycles, and it increased by 18% compared with that of pristine NCM811 after 100 cycles within 2.75–4.3 V at 0.5 C rate. This improved cycle performance can be attributed to the unique thin and continuous Mg-Al-LDO nanosheets coated on NCM811, which not only inhibits HF corrosion and the residual alkali salt formation, but also reduces Ni2+/Li+ cation mixing. This method provides a new strategy for the surface modification of nickel-rich layered cathode materials.

Saline water is an alternative resource that could be used to meet agriculture irrigation demands. Fouling, particularly that caused by calcium carbonate (CaCO3), often occurs in saline irrigation water distribution systems, and severely restricts the utilization of saline irrigation water. So far, water acidification is the common practice for avoiding CaCO3 fouling. However, this approach is often ineffective and regularly contributes to environmental pollution. This study investigated an effective practice to overcome CaCO3 fouling issues by regulating shear stress, temperature and ions in saline irrigation water irrigation systems. The effects of different near-wall shear stress at 0.05, 0.20, 0.40 and 0.60 Pa, coupling with temperature of 10, 20 30 and 40 oC and cations Mg2+ and Fe3+ were analyzed. Results demonstrated that the CaCO3 fouling rate was linearly increased at initial shear stress, while decreased at higher shear stress, and the highest fouling rate was observed at 0.40 Pa, ranging between 21.4%−80.3%. The coupling of temperature and cations with shear stress significantly (p 1) among different shear stress get larger with increasing temperature, while they decreased and increased with the addition of Mg2+ and Fe3+, respectively, when compared with pure solution of CaCO3. Refinement analysis showed the largest unit-cell volume and lattice parameter of calcite at shear stress of 0.40 Pa, resulting in a significant effect on distribution of fouling particle sizes and morphologies. Moreover, some anti-fouling measures were further proposed based on the formation behavior of CaCO3 fouling. These findings might provide a new perspective to control CaCO3 with potential implications for sustainable saline water management for irrigation.

In the present study, semi-solid billets of AZ91D magnesium alloy were prepared by employing the repetitive upsetting-extrusion (RUE) based strain induced melt activation (SIMA) process. Thixoforming experiments were performed using semi-solid alloys experiencing various RUE temperatures and semi-solid reheating temperatures. The microstructure characterization and microhardness of the thixoformed products were investigated. Microstructure examination results indicated that semi-solid globular microstructure ensuring good thixotropic filling performance was prepared by applying the RUE-based SIMA method. Thixoformed components with good surface quality were obtained. Compared with the original as-cast alloy, significant grain refinement and microhardness improvement occurred in the thixoformed components. And the mean grain sizes and microhardness values were measured to be in the ranges of 11.81–23.84 μm and Hv80.67–Hv90.65, respectively. By means of further comparison of microstructure and microhardness, the grain coarsening and microhardness reduction of the thixoformed components were verified by elevating the RUE deformation temperature and semi-solid remelting temperature. Furthermore, strengthening mechanisms during thixoforming involving the application of the RUE-based SIMA route were discussed in detail. The results showed that the comprehensive effect of fine grain strengthening, dispersion strengthening, and solid solubility strengthening should be responsible for microhardness improvement.

In order to investigate the construction of column-to-beam joints and to understand theeffect of recycled aggregate concrete (RAC) and cross-section of beams and columns on theseismic performance of recycled aggregate concrete-filled light steel tubular frame structure, fournew types of assembly joints were proposed in this paper. A low cyclic loading test of six framespecimens was carried out. The failure characteristic, load bearing capacity, hysteresis property,ductility, strength and stiffness degradation, and energy dissipation were analysed. The damageprocess of the specimen was simulated using the ABAQUS software, and the results agreed wellwith those obtained from the experiments. The results showed that the construction pathway of thejoints exhibited significant influence on the seismic performance of the frame. The proposedreinforced joint (using angle steel and stiffeners) significantly improved the bearing capacity,stiffness and energy dissipation capacity of the recycled aggregate concrete-filled steel tube frame.The seismic performance of the steel frame was improved, while the energy dissipation capacityincreased by 635.7% using RAC filled in the steel tubes. Finally, by appropriately increasing thesize of cross-section on the beams and columns can improve the bearing capacity, stiffness andductility of the structure.

In this paper, numerical simulations of fractured vertical well in low-permeable oil reservoir are carried out and two issues: threshold pressure gradient (TPG) in reservoir matrix and proppant distribution in hydraulic fractures are focused on. A physical definition of effective fracture length (EFL) is presented to evaluate the fracture effectiveness due to uneven proppant distribution. In terms of numerical processing for TPG, based on the subsurface Darcy's flow module in COMSOL Multiphysics, an effective numerical simulation method is adopted by substituting the gravitational acceleration vector in Darcy's law (Liu et al., 2019b). The simulation results show that, proppant distribution has great influence on fracture effectiveness. Unappealing proppant distribution can reduce effective fracture length by 49.6%, which is negative for low-permeable oil reservoir development. TPG in reservoir matrix mainly affects the moving boundary and pressure-disturbed area in reservoir. When TPG in matrix reduces from 0.02 MPa/m to 0 MPa/m, the distance of moving boundary at 300 days could increase for almost double and pressure-disturbed area enlarged drastically for around 74%. Furthermore, a heterogenous low-permeable oil with secondary fracture networks is designed to study the joint effect of TPG and proppant distribution. If we neglect these two factors, cumulative oil rate will be greatly overestimated by 38.6% at 1000 days. At the same time, the existence of natural fractures could also affect the streamline distribution in low-permeable oil reservoir and contribute to fluid flow in reservoir.

Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor-sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor-sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P

(1) Background: Though X-ray excited photodynamic therapy (X-PDT) breakthrough the bottom neck of PDT application in deep tumor by overcoming light penetration depth limitation, the quantum yield of the hydrophilic X-PDT nanoparticles (NPs) still hampered its further application in vivo. Thus, establishing a proper hydrophilic decoration method which can maximally maintain the quantum yield of X-ray excited luminescent NPs is of urgent demand. (2) Methods: We synthesized NaGdF4: [Formula: see text] (NGF) as X-ray excited luminescent NPs and conducted hydrophilic decoration by two hydrophilic ligands, polyethylene glycol-NH2 (PEG) and cysteamine (Cy) via place exchange reaction, and coupled with photosensitizer (MC540) to form a X-PDT nanosystem. We also conducted experiments in vitro and in vivo to evaluate the efficacy of the X-PDT system. (3) Results: Both PEG and Cy decoration NPs presented excellent emission intensity, which could well excite the coupled photosensitizer MC540 to generate significant X-PDT efficacy under low-dose X-ray radiation. Especially for the NGF-Cy-MC540 treatment group, the cell viability reduced to [Formula: see text]% under 0.3[Formula: see text]Gy radiation and [Formula: see text]% under only 0.1[Formula: see text]Gy radiation, which is the lowest radiation dosage in the literature reports so far. In vivo experiment showed about 36% of tumor inhibition rate under 0.3[Formula: see text]Gy X-ray. Besides, no biotoxicity was observed in NGF groups even in high concentrations, demonstrating good biocompatibility. (4) Conclusions: The hydrophilic decoration method by Cy or PEG via place exchange reaction may pave a brand new way and strategy for X-PDT further clinical application.

This paper analyzes the influence of solar radiation on the prestressed concrete wide box girder with a large cantilever. The experimental research is carried out by arranging the embedded deformation monitoring sensor, and the actual temperature deformation curve of the large cantilever box girder subjected to solar radiation is obtained. Besides, the deformation calculation model of box girder under the influence of solar radiation is established by ANSYS finite element software, so as to obtain the deformation distribution of large cantilever prestressed concrete under solar radiation. Calculation results are fitting well in with the actual tested results, with an average error of 7.97%. As the boundary conditions are quite ideal, the tested results tend to be larger. Relative studies can provide some guidance and suggestions for the deformation control and design of this type of bridge.

The transport and deposition of particulate materials through fractures is widely involved in environmental engineering and resource development engineering. A 3D Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) coupling method was used to investigate the particle and fluid flow. The Gauss Model was applied to construct the rough surfaces. First, the numerical results were compared with the previous results and reasonable agreements were obtained. Second, the results indicated a novel flow pattern of particles in rough fractures. Then, a comprehensive particle sedimentary analysis indicated that the deposition distance of particles was inversely proportional to the particle size and density ratio. In addition, the particle deposition rates were increased by the mean roughness and there was an uneven sediment distribution impacted by roughness. Reasons for this uneven sediment distribution were analyzed in detail. Moreover, the bridge plugs of particles considering the closure of fractures were simulated as well. A part of particulate materials would be filtered at the inlet due to size effect and the transport distance of entered particles decreased significantly when the particle was large. A critical particle radius (R

In the paper, the study on the exact analytical solution of the moving boundary problem of one-dimensional Bingham fluid seepage flow is extended from the infinite long porous media (Liu et al., 2012) to the finite long porous media. Two exact analytical solutions are presented by appropriately relying on some methods of mathematical physics and mathematical techniques. One is for the model with finite closed outer boundary condition; the other is for the model with finite constant pressure outer boundary condition. The existence and the uniqueness of the exact analytical solutions are also strictly proved theoretically. In addition, the numerical solutions of the two models by the finite difference method are also provided. Through the comparison, it is found that these exact analytical solutions have very excellent agreement with the numerical solutions although few terms of the infinite function series existent in the exact analytical solutions have to be retained for the calculation. Furthermore, for the two models, the effect of the threshold pressure gradient on the transient pressure and the transient pressure derivative at the inner boundary for the whole flow process is analyzed through the analytical solutions. Finally, through the comparison of the relevant model solutions, it is concluded that it is very necessary to incorporate the process of moving boundary for the modeling of non-Darcy Bingham fluid flow in finite long porous media with threshold pressure gradient; otherwise, large errors can be introduced in predicting the transient pressure and the transient pressure derivative in the porous media. The presented work can support solid theoretical foundations for the experiment design of measuring the threshold pressure gradient and the pressure transient analysis in the field of inverse problems in the petroleum engineering, which have been widely involved in the development of low-permeable oil reservoirs and heavy oil reservoirs.

Proppants are used to resist fracture closure during hydraulic fracking treatments. Understand the proppant transport and distribution characteristics in fracture and fracture network become a meaningful topic for its effects on the conductivities of fractures. Since experiments are expensive, and it is also difficult to consider various conditions and detect the movement of particles during experiments, numerical simulation methods are often applied. In this work, the coupled Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) was implemented to investigate the factors affecting proppant distribution in fracture and fracture networks. First, the CFD-DEM model was built for proppant flow and settlement. We validated the model by comparing with the published numerical simulation result. After that, we designed a series of cases to investigate the effects of fracture closure, injection velocity and no-uniform opening of the inlet on proppant distribution in a single fracture. Then, the effects of proppant diameter, density and perforation height differences on proppant sorting were studied. Next, we computed the proppant transport in fracture networks considering the aperture difference, the orientation of branch fractures and leak-off in fracture tips. The simulation results in this paper can help engineers to understand the transport and distribution of proppants visually in the fracture and fracture networks in unconventional reservoirs.

Recycle Aggregate Concrete (RAC) is a common “green” product used for a variety of purposes, although the durability and strength of the material still need more research to adequately determine influences on these parameters. The failure pattern, punching bearing capacity, and deflection variation of wallboard of both ordinary concrete and RAC with various rebar reinforcement diameters and spacing were analyzed. Based on experimental data, the ABAQUS finite element analysis of the thin wallboard was performed, and the calculated results are in good agreement with the experimental results. The results show that the failure characteristics of ordinary concrete wallboards and RAC wallboards are similar, but the brittleness of the RAC specimens is more significant. Under the same reinforcement ratio, concrete material, whether new or recycled, had little effect on the punching bearing capacity of the specimens. In the case of a low reinforcement ratio, increasing the reinforcement ratio (decreasing the spacing of steel bars) can effectively improve the bearing capacity of the wallboard. Under the same reinforcement ratio, the wallboard with larger diameter and larger spacing has a higher bearing capacity and less deformation after failure.

In this study, the cyclic behaviors of low rise concrete shear walls using recycled coarse or fine aggregates were investigated. Eight low rise Recycled Aggregates Concrete (RAC) shear wall specimens were designed and tested under a cyclic loading. The following parameters were varied: replacement percentages of recycled coarse or fine aggregates, reinforcement ratio, axial force ratio and X-shaped rebars brace. The failure characteristics, hysteretic behavior, strength and deformation capacity, strain characteristics and stiffness were studied. Test results showed that the using of the Recycled Coarse Aggregates (RCA) and its replacement ratio had almost no influence on the mechanical behavior of the shear wall; however, the using of Recycled Fine Aggregates (RFA) had a certain influence on the ductility of the shear wall. When the reinforcement ratio increased, the strength and ductility also increased. By increasing the axial force ratio, the strength increased but the ductility decreased significantly. The encased brace had a significant effect on enhancing the RAC shear walls. The experimental maximum strengths were evaluated with existing design codes, it was indicated that the strength evaluation of the low rise RAC shear walls can follow the existing design codes of the conventional concrete shear walls.

Aiming at the problem of navigation error caused by unified earth model in great circle route planning using sphere model and modern navigation equipment using ellipsoid mode, a method of great ellipse route planning based on space vector is studied. By using space vector algebra method, the vertex of great ellipse is solved directly, and description of great ellipse based on major-axis vector and minor-axis vector is presented. Then calculation formulas of great ellipse azimuth and distance are deduced using two basic vectors. Finally, algorithms of great ellipse route planning are studied, especially equal distance route planning algorithm based on Newton-Raphson(N-R) method. Comparative examples show that the difference of route planning between great circle and great ellipse is significant, using algorithms of great ellipse route planning can eliminate the navigation error caused by the great circle route planning, and effectively improve the accuracy of navigation calculation.

In order to quantitatively evaluate the shear-bearing capacity of shear connectors of square concrete filled steel tube (CFST), push-out tests on 14 square CFSTs with shear connectors have been carried out. Among the 14 CFSTs, there are 13 specimens with steel plate connectors and one specimen with steel bar connectors. The following factors are investigated to figure out their influences on the performance of CFSTs, which are the width to thickness ratio of steel tube, thickness of steel plate, length of steel plate, strength of concrete, welding condition of steel plate, number of steel plate layer and interlayer spacing. The test results show that the ultimate bearing capacity and the elastic stiffness increase with decreasing width to thickness ratio of the steel tube, and increasing thickness and length of the steel plate. With increasing concrete strength, the ultimate bearing capacity also increases. However, the welding condition has no effect on the ultimate bearing capacity. The ultimate bearing capacity of the CFST with double-layer steel plate is greater than that with single-layer steel plate. The ultimate bearing capacity of steel bar type shear connector is 87% greater than that of the steel plate type shear connector, and the steel bar specimen shows good ductility. A formula for calculating the shear-bearing capacity of shear connectors has been developed, and the calculated shear-bearing capacities are in good agreement with the test data.

Angiogenesis is an essential process for tissue growth and embryo development. However, inflammation, abnormal wound healing, vascular diseases, and tumor development and progression can result from inappropriate angiogenesis. Lipopolysaccharide (LPS) can activate various cells and alter endothelium function and angiogenesis. This study investigated the underlying molecular events involved in LPS-induced angiogenesis and revealed a novel strategy for controlling abnormal angiogenesis. LPS treatment promoted wound healing and tube formation in human umbilical vein endothelial cell (HUVEC) cultures and induced their expression of miR-146a. miR-146a was previously shown to regulate angiogenesis in HUVECs. Knockdown of miR-146a expression antagonized LPS-induced angiogenesis in vitro. Moreover, bioinformatic analyses predicted TGF-β1 as a target gene for miR-146a, which was confirmed by aluciferase reporter assay. Expression of miR-146a in HUVECs resulted in downregulation of TGF-β1 in HUVECs, whereas a miR-146a inhibitor upregulated the expression of TGF-β1 and TGF-β1 downstream proteins, such as phosphoraylation-Smad2 and plasminogen activator inhibitor type 1 (PAI-1). Furthermore, the TGF-β1 signaling inhibitor SB431542 impaired the ability of miR-146a knockdown to suppress LPS-induced angiogenesis. Thus, LPS-induced angiogenesis of HUVECs functions through miR-146a upregulation and TGF-β1 inhibition. This study suggests that knockdown of miR-146a could activate TGF-β1 signaling to inhibit angiogenesis as a potential therapy for angiogenesis-related diseases.

Microencapsulation is widely used to minimize the oxidation of fish oil products. This study compared the effects of different drying methods, for example, spray drying (SD), freeze drying (FD), and spray freeze drying (SFD) on the microencapsulation of fish oil. Spray drying (SD) is the most common method for producing fish oil microcapsules, and it has low operation cost and short processing time, while the product yield and quality are poor. Freeze drying (FD) can be used to produce oil microcapsules with high quality, but it takes long time and high overall cost for drying. Spray freeze drying (SFD) is a new method for the preparation of microcapsules, which combines the SD and FD processes to obtain high quality powder. The yield of powder reached 95.07% along with porous structure by SFD. The stability and slow-release property of SFD products were better than those of SD and FD, which showed that SFD improved product storage stability and potential digestibility.

In order to study the characteristics of the temperature field and variation law of steel pipe recycled aggregate concrete column in a fire hazard, this paper takes the thickness of steel pipe and the type of concrete material as the main parameters to carry out fire resistance test of six concrete steel columns simulated by ABAQUS and conducts finite element analysis of the temperature field inside the test piece. The result shows that both the steel pipe recycled concrete column and the ordinary steel tube concrete column have a temperature platform during heating, and their temperature rise is feature hysteresis; the thickness of the steel pipe has little effect on the internal temperature rise while the concrete material is the main factor affecting the heating rate, so steel pipe recycled aggregate concrete column is better fire-resistant. The constitutive model based on the modified parameters in European EC4 specification is used for finite element analysis, and the FEM simulation result is well fitted with the experimental data.

Medical condition of commercial driving license drivers (CDL drivers) has a direct influence on public traffic safety. Recently, a series of traffic accidents, caused by sudden giddiness of drivers, has reflected that this influence is not always on a positive level. Analyzing the feasibility and development of the current declaration mode for drivers’ medical condition based on laws and regulations, management mode, medical method and operational program, this paper suggests a set of safety loophole screening methods of CDL drivers’ medical condition.

This paper summarizes an engineering experience of solving the problem of thermal cracking in mass concrete by using a large project, Zhongguancun No.1 (Beijing, China), as an example. A new method is presented for controlling temperature cracks in the mass concrete of a foundation. The method involves controlled cycles of water circulating between the surface of mass concrete foundation and the atmospheric environment. The temperature gradient between the surface and the core of the mass concrete is controlled at a relatively stable state. Water collected from the well-points used for dewatering and from rainfall is used as the source for circulating water. Mass concrete of a foundation slab is experimentally investigated through field temperature monitoring. Numerical analyses are performed by developing a finite element model of the foundation with and without water circulation. The calculation parameters are proposed based on the experiment, and finite element analysis software MIDAS/CIVIL is used to calculate the 3D temperature field of the mass concrete during the entire process of heat of hydration. The numerical results are in good agreement with the measured results. The proposed method provides an alternative practical basis for preventing thermal cracks in mass concrete.

The seismic performance of recycled aggregate concrete (RAC) composite shear walls with different expandable polystyrene (EPS) configurations was investigated. Six concrete shear walls were designed and tested under cyclic loading to evaluate the effect of fine RAC in designing earthquake-resistant structures. Three of the six specimens were used to construct mid-rise walls with a shear-span ratio of 1.5, and the other three specimens were used to construct low-rise walls with a shear-span ratio of 0.8. The mid-rise and low-rise shear walls consisted of an ordinary recycled concrete shear wall, a composite wall with fine aggregate concrete (FAC) protective layer (EPS modules as the external insulation layer), and a composite wall with sandwiched EPS modules as the insulation layer. Several parameters obtained from the experimental results were compared and analyzed, including the load-bearing capacity, stiffness, ductility, energy dissipation, and failure characteristics of the specimens. The calculation formula of load-bearing capacity was obtained by considering the effect of FAC on composite shear walls as the protective layer. The damage process of the specimen was simulated using the ABAQUS Software, and the results agreed quite well with those obtained from the experiments. The results show that the seismic resistance behavior of the EPS module composite for shear walls performed better than ordinary recycled concrete for shear walls. Shear walls with sandwiched EPS modules had a better seismic performance than those with EPS modules lying outside. Although the FAC protective layer slightly improved the seismic performance of the structure, it undoubtedly slowed down the speed of crack formation and the stiffness degradation of the walls.

In order to understand the effects of variation in consumption structure of bio-resource products on the ecological environment, in the case of Ordos City in Inner Mongolia, we explored ecological footprint (EF) based on sub-national (provincial) hectare, which was modified from global hectare, to analyze the characteristics of consumption structure of bio-resources and their ecological influence in 1995 and 2012 (before and after the project of “Return Grazing Land to Grassland”). The results showed that the consumption structure of bio-resource products tended towards multiplication in Ordos City. The food consumption transformed from mainly grain-oil and meat-milk-eggs to a variety of foods; in addition, the consumption of firewood was replaced by fossil fuels gradually. Compared with 1995, the EFs of grain-oil and firewood consumption were reduced by 53.23% and 86.49%, and the increase of melons-vegetables was 44.97% in 2012, respectively. The EF of bio-resource product consumption was mainly relied on cultivated land, which included grain-oils, melons-vegetables and meat-milk-eggs. The EFs of these productions consumption on cultivated land increased or decreased to different extents before and after the “Return Grazing Land to Grassland”. The contribution rate of grain-oils on cultivated land decreased from 40.17% (in 1995) to 21.74% (in 2012), while the contribution rates of melons-vegetables and meat-milk-eggs increased. The Ecological Deficit (ED) of Ordos City in 2012 reached 2.7384 hm2/cap lower than the ED in 1995 (3.4382 hm2/cap), and eco-efficiency in 2012 also was obviously higher than the level in 1995. This indicated that the disturbance and consumption of human activity on the natural resources, and their influences on ecological environment declined, and the utilization efficiency of resources and environment has been significantly improved. However, the ED rate was still very high due to the floating population; approximately 548.83×104 hm2 biological productive land area will be needed to satisfy the total population's demands of consumption of bio-resource products in Ordos City in 2012. The research demonstrated the transformation of consumption structure of bio-resources products has benefit to ease the ecological stress in Ordos City. Furthermore, the increasing of ecological efficiency will play a significant role in improving the human-land relationship, as well as the ecological environment.

In view of the problem that the traditional sub pixel edge extraction method is obviously deviated from the real edge near the corner. A new algorithm is proposed. In this paper, the corner protection function is added to the level set energy functional, which makes that the evolution of level set function is restricted at the corner, therefore this algorithm can improve the accuracy of edge extraction near the corner. The sub pixel edge extraction results of simulated and real images show that the proposed method is more accurate at the edge of the corner.

This paper summarizes an engineering experience of solving the problem of thermal cracking in mass concrete by using a large project, Zhongguancun No.1 (Beijing, China), as an example. A new method is presented for controlling temperature cracks in the mass concrete of a foundation. The method involves controlled cycles of water circulating between the surface of mass concrete foundation and the atmospheric environment. The temperature gradient between the surface and the core of the mass concrete is controlled at a relatively stable state. Water collected from the well-points used for dewatering and from rainfall is used as the source for circulating water. Mass concrete of a foundation slab is experimentally investigated through field temperature monitoring. The temperature field of the mass concrete during the entire process of heat of hydration are analyzed in detail. The proposed method provides an alternative practical basis for preventing thermal cracks in mass concrete.

Brief electrical stimulation has been shown to be effective in promoting neuronal regeneration following peripheral nerve injury. These effects are thought to be mediated largely by the upregulation of the expression of brain-derived neurotrophic factor (BDNF) in spinal cord neurons. However, the molecular mechanisms by which electrical stimulation can promote BDNF expression are not known. The mechanism involved in BDNF expression after electrical stimulation was explored in this study. Immunohistochemistry and Western blotting were used to test BDNF expression. Confocal microscopy was utilized to study intracellular Ca(2+) volume. Immunohistochemistry and Western blotting confirmed that brief electrical stimulation increased BDNF expression in spinal cord neurons both in vivo and in vitro. Treatment of cultured neurons with nifedipine, an inhibitor of voltage-gated calcium channels, significantly reduced the BDNF increase produced by electrical stimulation, and an inhibitor of Erk completely abolished the effect of electrical stimulation. Levels of BDNF expression in the presence of the Erk inhibitor were lower that in unstimulated and untreated controls, indicating that Erk activation is required to maintain baseline levels of BDNF. Confocal microscopy using a Ca(2+)-sensitive fluorochrome revealed that electrical stimulation is accompanied by an increase in intracellular Ca(2+) levels; the increase was partly blocked by nifedipine. These findings argue that electrical stimulation increases BDNF expression in spinal cord neurons by activating a Ca(2+)- and Erk-dependent signaling pathways.