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Three-dimensional grapheme-doped carbon cryogels (CCs) with high specific surface area have been prepared via the self-assembly of graphene oxide (GO) sheets and resorcinol (R)-formaldehyde (F) monomers. The porosity of the composite CCs can be regulated from high mesoporosity to microporosity by adjusting the mass ratio of GO sheets to RF monomers. When the loading amount of GO sheets is 1.3 wt.% in the precursor mixture, the specific surface area of the resulting composite CCs is up to 1178 m2 g−1, which is much higher than that of the neat RF CCs (766 m2 g−1). Furthermore, the as-prepared composite CC electrode displays a high specific capacitance (205 F g−1 at 1.0 mV s−1) and superior rate capability compared to the neat RF CCs.

We have recently developed a new modeling capability to embed the implicit particle-in-cell (PIC) model iPIC3D into the Block-Adaptive-Tree-Solarwind-Roe-Upwind-Scheme magnetohydrodynamic (MHD) model. The MHD with embedded PIC domains (MHD-EPIC) algorithm is a two-way coupled kinetic-fluid model. As one of the very first applications of the MHD-EPIC algorithm, we simulate the interaction between Jupiter's magnetospheric plasma and Ganymede's magnetosphere. We compare the MHD-EPIC simulations with pure Hall MHD simulations and compare both model results with Galileo observations to assess the importance of kinetic effects in controlling the configuration and dynamics of Ganymede's magnetosphere. We find that the Hall MHD and MHD-EPIC solutions are qualitatively similar, but there are significant quantitative differences. In particular, the density and pressure inside the magnetosphere show different distributions. For our baseline grid resolution the PIC solution is more dynamic than the Hall MHD simulation and it compares significantly better with the Galileo magnetic measurements than the Hall MHD solution. The power spectra of the observed and simulated magnetic field fluctuations agree extremely well for the MHD-EPIC model. The MHD-EPIC simulation also produced a few flux transfer events (FTEs) that have magnetic signatures very similar to an observed event. The simulation shows that the FTEs often exhibit complex 3-D structures with their orientations changing substantially between the equatorial plane and the Galileo trajectory, which explains the magnetic signatures observed during the magnetopause crossings. The computational cost of the MHD-EPIC simulation was only about 4 times more than that of the Hall MHD simulation.

Automatic multi-pass route planning is one of key technologies for thick plate in robotic metal active gas (MAG) arc welding. In this research, a scheme for the extracting feature points of the weld seam profile to implement automatic multi-pass route planning, and guidance of the initial welding position in each layer during MAG arc welding, is presented. It consists of two steps: first a vision sensor based on structured light is employed to capture laser stripes and molten pools simultaneously within the same frame, and the laser stripe, forming the weld seam profile is detected by a visual attention model based on saliency. Then a methodology of polynomial fitting plus derivatives for feature point extraction of the weld seam profile is suggested. With respect to the effectiveness of highlighting the laser stripe, the proposed model is much better than the classic ones in this field, whereas the feature point extraction methodology in this paper outperforms typical template matching. Finally, the performance of the proposed scheme is demonstrated on different weld seam images captured in different layers and different welding experiments. New vision sensor captures laser stripes and molten pools simultaneously.A visual attention model for detecting weld seam profiles is proposed.Three kinds of feature points of weld seam profiles can be extracted.Different images captured in different layers validate the proposed methods.The extracted feature points can be used for multi-pass route planning.

We present a new fifth-order accurate finite difference method for hyperbolic equations on block-adaptive curvilinear grids. The scheme employs the 5th order accurate monotonicity preserving limiter MP5 to construct high order accurate face fluxes. The fifth-order accuracy of the spatial derivatives is ensured by a flux correction step. The method is generalized to curvilinear grids with a free-stream preserving discretization. It is also extended to block-adaptive grids using carefully designed ghost cell interpolation algorithms. Only three layers of ghost cells are required, and the grid blocks can be as small as 6 × 6 × 6 cells. Dynamic grid refinement and coarsening are also fifth-order accurate. All interpolation algorithms employ a general limiter based on the principles of the MP5 limiter. The finite difference scheme is fully conservative on static uniform grids. Conservation is only maintained at the truncation error level at grid resolution changes and during grid adaptation, but our numerical tests indicate that the results are still very accurate. We demonstrate the capabilities of the new method on a number of numerical tests, including smooth but non-linear problems as well as simulations involving discontinuities.

Robust porous SiO2/Si/graphene/C microspheres have been successfully synthesized by a simple two-step process of ultrasonic spraying and partial magnesiothermic reduction. The 3-D porous microspheres consist of Si/SiO2 nanoparticles (around 5–10 nm) covered by a layer of carbon and connected by graphene. We explored the electrochemical properties of the porous microspheres as an anode for lithium ion batteries (LIBs). In SiO2/Si/graphene/C microspheres, numerous pores could leave enough room for volume expansion and contraction of silicon during lithiation and delithiation, and provide large space voids for electrolyte reserves. Meanwhile, graphene plays a role in reinforcing the porous structure. The prepared sample shows superior cyclability with a discharge capacity of 1104.9 mA h g−1 in the second cycle and 1141.6 mA h g−1 over 200 cycles at a current density of 0.1 mA cm−2. The capacity retention is more than 100%, making it very promising as a future LIBs anode.

The telomerase is responsible for adding telomeric repeats to chromosomal ends and consists of the reverse transcriptase TERT and the RNA subunit TERC. The expression and activity of the telomerase are tightly regulated, and aberrant activation of the telomerase has been observed in >85% of human cancers. To better understand telomerase regulation, we performed immunoprecipitations coupled with mass spectrometry (IP-MS) and identified cold inducible RNA-binding protein (CIRP or hnRNP A18) as a telomerase-interacting factor. We have found that CIRP is necessary to maintain telomerase activities at both 32°C and 37°C. Furthermore, inhibition of CIRP by CRISPR-Cas9 or siRNA knockdown led to reduced telomerase activities and shortened telomere length, suggesting an important role of CIRP in telomere maintenance. We also provide evidence here that CIRP associates with the active telomerase complex through direct binding of TERC and regulates Cajal body localization of the telomerase. In addition, CIRP regulates the level of TERT mRNAs. At the lower temperature, TERT mRNA is upregulated in a CIRP-dependent manner to compensate for reduced telomerase activities. Taken together, these findings highlight the dual roles that CIRP plays in regulating TERT and TERC, and reveal a new class of telomerase modulators in response to hypothermia conditions.

Carbon-coated Li4Ti5O12 and lithiated Li4+xTi5O12 anode materials have been synthesized using nanosized anatase TiO2 and commercial TiO2 with mixed structure as Ti sources, respectively. Microstructural investigation indicates that Li4Ti5O12 and Li4+xTi5O12 are covered by amorphous carbon layers with thickness of 2–3 nm. Their electrochemical performance has been evaluated, which indicates that an amount of active Li ions have been pre-stored in the Li4+xTi5O12 lattice during solid-state synthesis, resulting in its first-cycle coulombic efficiency over 100%. Further, Li4+xTi5O12/C exhibits higher cyclic capacities than Li4Ti5O12/C at different current density. The reversible charge capacity retention of Li4+xTi5O12/C reaches 98.5% after 100 cycles, which indicates that Li4+xTi5O12/C is promising candidate anode material for long lifetime lithium-ion batteries. The formation mechanism of Li4+xTi5O12/C has been discussed, in which the nanosized anatase TiO2 with high chemical activity and the carbon coating play key roles for the formation of Li4+xTi5O12/C.

Here, we report a nano-sized red phosphorous/biomass-derived porous carbon (P@BDPC) which is employed as anode materials for lithium ion batteries (LIBs) via a facile vaporization−condensation−conversion strategy (VCC) with tobacco stem as the carbon precursor. The biomass-derived porous carbon not only acts as the host of red phosphorus to enhance the electrical conductivity, but also minimizes the volume expansion (≈400%) during cycling. The obtained P@BDPC composite with a high red phosphorus content (62.1 wt%) delivers a high specific capacity of 1689 mA h g−1 at 500 mA g−1 with an initial Coulombic efficiency (ICE) of 91.7% and superior rate capability of 599 mA h g−1 at 30 A g−1. Furthermore, a high reversible capacity of 918 mA h g−1 can be retained over 600 cycles at 5 A g−1, indicating a remarkable cycle stability. More importantly, the introduction of agriculture waste-tobacco stem contributes to building low-cost, high-performance anode materials.

Background Allergic conjunctivitis (AC), a common eye inflammation that affects patients’ health and quality of life, is still a therapeutic challenge for ophthalmologists. Tofacitinib, a new Janus kinase (JAK) inhibitor, has been successfully used in the treatment of several disorders. Nonetheless, its effect in AC and the potential anti-allergic mechanisms are still unclear. The objective of the current study was to explore the roles of tofacitinib in preventing AC and elucidate the potential underlying mechanisms. Methods Tofacitinib was used topically in BALB/c mice with experimental allergic conjunctivitis (EAC). Ocular allergic symptoms and biological modifications were examined. To assess the anti-allergic mechanisms of tofacitinib, RBL-2H3 cells and HUVECs were cultured in vitro. The inhibitory effects and mechanisms of tofacitinib were studied and measured by real-time quantitative PCR, ELISA, western blot analysis, and flow cytometry. Results Topical administration of tofacitinib reduced the clinical symptoms of OVA-induced EAC, with a substantial mitigation in inflammatory cell infiltration, histamine release, and TNF-α mRNA as well as IL-4 mRNA expression. In vitro, tofacitinib repressed the degranulation and cytokine production in RBL-2H3 cells and reduced histamine-induced vascular hyperpermeability. The underlying mechanism might involve the downregulation of phosphorylation of JAK3/STATs signaling molecules in RBL-2H3 cells and HUVECs. Conclusions Our findings provide evidence that tofacitinib prevented EAC by targeting the JAK3/STATs pathway. We recommend the use of tofacitinib as an innovative approach for the treatment of AC.

The improper disposal of oily sludge and converter steel slag can be of great environmental concerns, herein, we proposed an innovative methodology by coupling the catalytic thermochemical conversion of oily sludge with the high-temperature reduction of steel slag, where the gas energy and iron resources can be recovered simultaneously. It was found out that the gas yield, iron reduction efficiency, as well as the carbon conversion, were positively correlated with the temperature, the amount of steel slag added and slag particle fineness. With the addition of steel slag, the carbon conversion increased from 76.6 % to 90.1 %, and the iron reduction efficiency increased from 38.5 % to 70.6 %. The phase and microstructure characterizations revealed that the iron-bearing phases (RO phase, Ca2Fe2O5) in steel slag were reduced into metallic iron by pyrolytic gaseous intermediate products (600−800 °C) and solid char (800−1000 °C). The in-situ reduced iron particles in turn acted as an efficient catalyst for cracking/reforming reactions, resulting in remarkable fuel gases, i.e. H2, CO evolution. Hence, the reduction of steel slag and the catalytic cracking/reforming of oily sludge were both enhanced. Furthermore, the technical-economic analysis in terms of material and energy balances was performed. It revealed that the proposed process was favorable for energy recovery and high added material production.

Class 2 CRISPR–Cas proteins have been widely developed as genome editing and transcriptional regulating tools. Class 1 type I CRISPR–Cas constitutes ~60% of all the CRISPR–Cas systems. However, only type I–B and I–E systems have been used to control mammalian gene expression and for genome editing. Here we demonstrate the feasibility of using type I–F system to regulate human gene expression. By fusing transcription activation domain to Pseudomonas aeruginosa type I–F Cas proteins, we activate gene transcription in human cells. In most cases, type I–F system is more efficient than other CRISPR-based systems. Transcription activation is enhanced by elongating the crRNA. In addition, we achieve multiplexed gene activation with a crRNA array. Furthermore, type I–F system activates target genes specifically without off-target transcription activation. These data demonstrate the robustness and programmability of type I–F CRISPR–Cas in human cells., Class 1 type I CRISPR–Cas systems have not been as extensively developed for genome engineering as Class 2 systems. Here the authors modify the Type I–F CRISPR–Cas system for transcriptional activation of gene expression.

The conductive additives are often used to improve the conductivity of the electrode in lithium iron phosphate battery. In this work, a series of carbon-based conductive slurries of acetylene black, carbon nanotubes and graphene were obtained by the ball milling method and applied to the cathodes of lithium iron phosphate batteries. The conductivity of the ternary conductive slurry reaches 11.98[Formula: see text]S[Formula: see text]cm[Formula: see text] and the result of Zeta potential indicates that the ternary conductive slurry has the best deposit stability. The average discharge capacity of lithium batteries with ternary conductive additive is 111.3[Formula: see text]mAh[Formula: see text]g[Formula: see text] at the current density of 10C, which is 1.9 times higher than that of acetylene black conductive additive batteries widely used nowadays. The specific capacity of the battery is 129.2[Formula: see text]mAh[Formula: see text]g[Formula: see text] after 200 cycles at the current density of 5C, and the capacity retention rate is 99.7%. The ternary conductive materials can form a continuous “point-line-surface” conductive network, increase the contact sites between lithium iron phosphate particles and conductive materials and provide a more efficient transmission path.

To obtain high-performance sulfur cathode for lithium-sulfur (Li-S) battery, porous graphitized carbon spheres with N doping have been fabricated via an in situ Fe catalysis as sulfur host. The in situ generated Fe nanoparticles play double roles as graphitization catalyst and pore template. The electrical conductivity of the graphitized sample (5.6 S cm−1) is about one order of magnitude higher than that of the amorphous carbon sample (0.63 S cm−1). Correspondingly, the pomegranate-like S@N-doped graphitized carbon cathode displays very good electrochemical performance. A capacity of 600 mAh g−1 is obtained after 150 charge/discharge cycles at a current density of 1 C with a sulfur content of 73 wt%. The pomegranate-like S@N-doped graphitized carbon is promising cathode candidate for high-performance Li-S battery.

We proposed a polyaniline-camphorsulfonic acid/titanium dioxide (PANI-CSA/TiO2) coated glass capillary tube sensor structure in this work. The PANI-CSA/TiO2 sensitive material was grown on the inner wall of silica glass capillary tube. A dynamic liquid phase deposition (DLPD) process was developed to fabricate the tube sensor samples. The optimum processing parameters, microstructures, morphology and gas detective performances of the PANI-CSA/TiO2 tube sensors were investigated. PANI-CSA/TiO2 capillary tube sensor samples (core size 1 mm, length 7 cm) with better properties were obtained at an optimum liquid flow rate of 0.62 mL min−1. The tube sensor shows response time of 84 s, response of 877 % and recovery time of 55 s for detecting 3 ppm NH3 gas while the plane sensor sample has response time of 152 s, response of 17.8 % and recovery time of 367 s. The capillary tube sensor exhibits convenience for detecting a small volume of gas sample. For a 1 mL, 0.1 ppm NH3 gas sample, the PANI-CSA/TiO2 capillary tube sensor exhibits 54 s response time, 454 % response while the plane-shaped sensor fails to detect.

With the rapid development of the information technologies in the financial field, extracting meaningful information from a massive amount of data is hugely significant for efficient business decision making. The recommendation system is an intelligent system that applies historical knowledge of users to infer their preferences and make a personalized recommendation. However, it suffers from the problem of time effect of user’s behaviour, which means a user’s interests may change over time. To overcome this problem, we propose a time effect based collaborative filtering approach to adaptively statistics the change of user preferences. Firstly, Item-based collaborative filtering is used to calculate rating similarity between items. Since an Item-based collaborative filtering algorithm doesn’t consider the time effect; next, the time decay function is proposed to statistics the change of user interests. Experimental results show that the proposed scheme retained higher accuracy compare to traditional collaborative filtering method.

Predicting variations in the near-Earth space environment that can lead to spacecraft damage and failure is one example of “space weather” and a big space physics challenge. A project recently funded through the Los Alamos National Laboratory (LANL) Directed Research and Development (LDRD) program aims at developing a new capability to understand, model, and predict Space Hazards Induced near Earth by Large Dynamic Storms, the SHIELDS framework. The project goals are to understand the dynamics of the surface charging environment (SCE), the hot (keV) electrons representing the source and seed populations for the radiation belts, on both macro- and micro-scale. Important physics questions related to particle injection and acceleration associated with magnetospheric storms and substorms, as well as plasma waves, are investigated. These challenging problems are addressed using a team of world-class experts in the fields of space science and computational plasma physics, and state-of-the-art models and computational facilities. A full two-way coupling of physics-based models across multiple scales, including a global MHD (BATS-R-US) embedding a particle-in-cell (iPIC3D) and an inner magnetosphere (RAM-SCB) codes, is achieved. New data assimilation techniques employing in situ satellite data are developed; these provide an order of magnitude improvement in the accuracy in the simulation of the SCE. SHIELDS also includes a post-processing tool designed to calculate the surface charging for specific spacecraft geometry using the Curvilinear Particle-In-Cell (CPIC) code that can be used for reanalysis of satellite failures or for satellite design.

Use of intravenous bisphosphonates has been demonstrated to improve clinical outcomes in children with osteogenesis imperfecta (OI). However, efficacy and safety of bisphosphonates in adults with OI remains unclear. Atypical femur fractures (AFF) are rare insufficiency fractures associated with long-term bisphosphonate use. We report on a 56 year old woman with OI type 1 and long-term bisphosphonate use who was diagnosed with multiple myeloma (MM) following a severe vertebral fracture. During workup, an asymptomatic incomplete AFF of the left femur diaphysis was noted. Multiple factors may have contributed to the occurrence of AFF, including bisphosphonate exposure, bowing of the proximal femur, as well as the intrinsic collagen defect of OI. To reduce the risk of skeletal complications from MM, intravenous pamidronate was administered in addition to chemotherapy, though in reduced dose and frequency. Orthopedic consultant recommended against prophylactic surgery for the AFF. Follow-up radiograph showed no progression of the AFF, though delayed healing was present. This case highlights the importance of close monitoring of patients on long-term bisphosphonate therapy who have additional risk factors for developing AFF, such as underlying genetic bone disorders or lower limb deformities. A multidisciplinary approach is recommended for optimal management of such complex patients.

Autoimmune uveitis (AU), a sight-threatening intraocular disorder, is still a challenge for ophthalmologists in clinic. Teriflunomide has been approved for multiple sclerosis (MS) in 2012 for its immunoregulatory function. However, the effect and mechanisms of teriflunomide in uveitis are still unknown. In this investigation, we used a murine model of non-infectious uveitis, experimental autoimmune uveitis (EAU), to explore the anti-inflammatory features of teriflunomide. Treatment with teriflunomide resulted in reduced clinical and pathological scores of retinal inflammations, accompanied by decreased intraocular infiltration of Th17 and Th1 cells in EAU mice. Meanwhile, teriflunomide treatment inhibited the proliferation and polarization of CD4+ T cells to Th17 and Th1 cells. Moreover, adoptive transfer of teriflunomide primed IRBP1-20-T cells failed to induce EAU. Interestingly, we found that teriflunomide suppressed the maturation and function of dendritic cells (DCs) both in vivo and in vitro. In conclusion, our findings suggest that teriflunomide alleviates inflammation in EAU mice by down-regulating Th17 and Th1 cells and suppresses the maturation and function of DCs for the first time.

Ischemic stroke is one of the main causes of death and disablement globally. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is established as a sensor of detecting cellular damage and modulating inflammatory responses to injury during the progress of ischemic stroke. Inhibiting or blocking the NLRP3 inflammasome at different stages, including expression, assembly, and secretion, may have great promise to improve the neurological deficits during ischemic stroke. The current review provides a comprehensive summary of the current understanding in the literature of the molecular structure, expression, and assembly of the NLRP3 inflammasome, and highlights its potential as a novel therapeutic target for ischemic stroke.

The Energy Conserving Semi-Implicit Method (ECSIM) introduced by Lapenta (2017) has many advantageous properties compared to the classical semi-implicit and explicit PIC methods. Most importantly, energy conservation eliminates the growth of the finite grid instability. We have implemented ECSIM in a different and more efficient manner than the original approach. More importantly, we have addressed two major shortcomings of the original ECSIM algorithm: there is no mechanism to enforce Gauss's law and there is no mechanism to reduce the numerical oscillations of the electric field. A classical approach to satisfy Gauss's law is to modify the electric field and its divergence using either an elliptic or a parabolic/hyperbolic correction based on the Generalized Lagrange Multiplier method. This correction, however, violates the energy conservation property, and the oscillations related to the finite grid instability reappear in the modified ECSIM scheme. We invented a new alternative approach: the particle positions are modified instead of the electric field in the correction step. Displacing the particles slightly does not change the energy conservation property, while it can satisfy Gauss's law by changing the charge density. We found that the new Gauss's Law satisfying Energy Conserving Semi-Implicit Method (GL-ECSIM) produces superior results compared to the original ECSIM algorithm. In some simulations, however, there are still some numerical oscillations present in the electric field. We attribute this to the simple finite difference discretization of the energy conserving implicit electric field solver. We modified the spatial discretization of the field solver to reduce these oscillations while only slightly violating the energy conservation properties. We demonstrate the improved quality of the GL-ECSIM method with several tests.

Osteosarcoma is an aggressive cancer of the skeletal system, which is associated with a poor prognosis due to the high recurrence rate. Although previous studies have revealed that competitive endogenous RNAs (ceRNAs) are involved in various biological processes in the physiology and development of osteosarcoma, the roles of ceRNAs in osteosarcoma recurrence remain largely unexplored. The present study constructed a ceRNA‑ceRNA network for osteosarcoma by systematically integrating matched expression profiles for microRNAs (miRNAs/miRs) and mRNAs, and identified two ceRNA‑mediated modules that were associated with recurrence in patients with osteosarcoma. A multivariate Cox regression analysis demonstrated that the recurrence‑free prognosis associated with the expression of the two modules was independent of other clinical factors. In addition, hsa‑miR‑335‑3p was identified as an upstream regulating factor for both modules. In conclusion, the results of the present study suggested that ceRNAs may act as potential therapeutic biomarkers for predicting the recurrence of osteosarcoma, and may help to identify patients with osteosarcoma at a high risk of recurrence, who may benefit from adjuvant therapy.

The research and refinement of papermaking wastewater treatment and reuse technology are important measures for energy conservation and emission reduction in the papermaking industry. This paper studied the process of biofilm formation and dissolved oxygen mass transfer of biofilms cultivated under different aeration intensities and attempted to enhance the biofilm reactor performance. The removal efficiencies of the chemical oxygen demand, total nitrogen, and ammonia nitrogen through biofilm treatment in two parallel biofilm reactors were higher under the larger aeration intensity (8 L/min) than under the smaller intensity (4 L/min). Macroscopically, this reflected the effect of dissolved oxygen on nitrogen removal. Microscopically, in terms of the dissolved oxygen profiles inside of the biofilms determined using a microelectrode probe, both aerobic and anaerobic layers occurred inside the biofilms, which suggested that simultaneous nitrification and denitrification occurred. The different aeration intensities led to differences in the internal and external dissolved oxygen concentrations in the biofilms, which affected the biofilm growth. This led to different micro-structures, and so the internal metabolism and wastewater treatment performance of the biofilms were not identical.

The casing damage has been a big problem in oilfield production. The current detection methods mostly are used after casing damage, which is not very effective. With the rapid development of China’s offshore oil industry, the number of offshore oil wells is becoming larger and larger. Because the cost of offshore oil well is very high, the casing damage will cause huge economic losses. What’s more, it can also bring serious pollution to marine environment. So the effective methods of detecting casing damage are required badly. The accumulation of stress is the main reason for the casing damage. Magnetic anisotropy technique based on counter magnetostriction effect can detect the stress of casing in real time and help us to find out the hidden dangers in time. It is essential for us to prevent the casing damage from occurring. However, such technique is still in the development stage. Previous studies mostly got the relationship between stress and magnetic signals by physical experiment, and the study of physical mechanism in relative magnetic permeability connecting the stress and magnetic signals is rarely reported. The present paper uses the ANSYS to do the three-dimensional finite element numerical simulation to study how the relative magnetic permeability works for the oil casing model. We find that the quantitative relationship between the stress’s variation and magnetic induction intensity’s variation is: Δδ = K* ΔB, K = 8.04×109, which is proved correct by physical experiment.

Carbon-coated spinel-structured Li1-xTi2O4 (0

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing. Electronic supplementary material The online version of this article (doi:10.1007/s13238-015-0153-5) contains supplementary material, which is available to authorized users.

This paper presents a method of autonomously detecting weld seam profiles from molten pool background in metal active gas (MAG) arc welding using a novel model of saliency-based visual attention. First, a vision sensor based on structured light is employed to capture laser stripes and molten pools simultaneously in the same frame. Second, to effectively detect the weld seam profile from molten pool background for next autonomous guidance of initial welding positions and seam tracking, a model of visual attention based on saliency is proposed. With respect to the enhanced effect of saliency, the proposed model is much better than the classic models in the field. According to the comprehensive saliency map created by the proposed model, the weld seam profile can be extracted after threshold segmentation and clustering are applied to it in turn. Third, different weld seam images are used to demonstrate the robustness of the proposed methodology and last, to evaluate the performance of the proposed method, a measure called profile extraction rate (PER) is computed, which shows that the extracted weld seam profile can basically meet the requirements of seam tracking and the guidance of welding torches.

In order to understand the fracture mechanisms of bone subjected to external force well, an experimental study has been performed on the bovine bone by carrying out the three-point bending test with 3D digital image correlation (DIC) method, which provides a noncontact and full field of displacement measurement. The local strain and damage evolution of the bone has been recorded real time. The results show that the deflection measured by DIC agrees well with that obtained by the displacement sensor of the mechanical testing machine. The relationship between the deflection and the force is nearly linear prior to reaching the peak strength which is about 16 kN for the tested bovine tibia. The full-field strain contours of the bone show that the strain distribution depends on not only the force direction, but also the natural bone shape. The natural arched-shape bovine tibia bone could bear a large force, due to the tissue structure with high strength, and the fracture propagation process of the sample initiates at the inner side of the bone first and propagates along the force direction.

In this paper, a novel double-sided gas metal arc welding procedure was developed to weld 50 mm thick, low-alloy high-tensile steel. The good weld joint without visible flaws can be obtained. The microstructure and mechanical properties were investigated in detail. The results show that the base metal metallographic microstructure mainly consists of tempering lath martensite and a small amount of granular bainite. The fusion zone is mainly composed of acicular ferrite and lath martensite while the microstructure of the welded bead is composed of acicular ferrite and a small amount of granular bainite. The average hardness value of the welded bead (384.9 HV) is higher than the base metal (282.2 HV), but lower than the heat-affected zone. The average tensile strength of the welded specimens (862.73 MPa) reaches 98.04 % of the base metal (880 MPa). No crack produced when the samples have been bended to 180° and the welding joints all have better plastic property. The impact absorbing energies in FL + 2 mm and FL + 5 mm are higher than those in WC and FL. The fracture modes of WC and FL are cleavage fracture and those of FL + 2 mm and FL + 5 mm are ductile fracture. Consequently, the double-sided GMAW is a high-efficiency welding method without back chipping which has certain advantages and possibility in welding thick plates.

Flowerlike graphene-based particles had been successfully synthesized from the suspension of graphene oxide (GO) in the aqueous solution of sucrose by one-pot hydrothermal carbonization approach. Porous carbon from sucrose prompted the evolution of graphene from flat-shaped to flowerlike curved morphology, which was confirmed by the observation of scanning electron microscopy and transmission electron microscopy. The graphene-based particles possess large pore volume (0.69 cm 3 g −1 ) and surface area (470.5 m 2 g −1 ), which is about 6 times greater than that of carbonized graphene sheets (79.2 m 2 g −1 ). Electrochemical investigation indicated that the specific capacitance of the particles reached 162 F g −1 at current density of 0.1 A g −1 in 30 wt% KOH aqueous electrolytes and the capacitance maintenance achieved 90% as the current density enlarged 50 times. The keys to the ideal capacitive performance are the abilities to make full utilization of specific surface area of graphene and ensure a quick kinetic process for the diffusion of ions within curved graphene particles with considerable open edges.

Two low-cost synthesis routes have been developed to fabricate carbon-coated Li4Ti5O12 by using H2TiO3 instead of anatase TiO2 as Ti source through solid-state reaction process. One route is a direct solid mixture of H2TiO3, Li2CO3 and pitch followed by high-temperature solid-state reaction. The other includes mixture of H2TiO3 and Li2CO3 with pitch dissolved in furanidine under vacuum and the same solid-state reaction procedure is followed after the mixture is totally dried. Microstructural investigations indicate that H2TiO3 exhibits secondary aggregates morphology with primary particle sizes of 10–20 nm. Carbon-coating layers with thickness of 2–3 nm have been observed on Li4Ti5O12 synthesized by the two routes. Cyclic performance, rate capability and electrochemical impedance spectrum of the two Li4Ti5O12/C composites have been performed, which indicate that Li4Ti5O12/C obtained by furanidine-assisted mixture exhibits better electrochemical performance than Li4Ti5O12/C synthesized by direct solid mixture. The possible reasons have been discussed. The low-cost synthesis routes of Li4Ti5O12/C using H2TiO3 as Ti source are expected to be more competitive than the traditional one for practical applications.

We investigate the use of artificially increased ion and electron kinetic scales in global plasma simulations. We argue that as long as the global and ion inertial scales remain well separated, (1) ...

Spermatids undergo the final steps of maturation during spermiogenesis, a process that necessitates extensive rearrangement of organelles such as the mitochondria. Male infertility has been linked to mitochondrial disorder, for example, hypospermatogenesis and asthenozoospermia. However, the mechanisms that regulate mitochondrial dynamics during spermiogenesis remain largely unknown. We found the glycerol kinase (Gyk)-like proteins glycerol kinase-like 1 (Gykl1) and glycerol kinase 2 (Gk2) were specifically localized to the mitochondria in spermatids. Male mice deficient in either Gykl1 or Gk2 were infertile due to dysfunctional spermatozoa, which exhibited unregulated ATP production, disordered mitochondrial sheath formation, abnormal mitochondrial morphology, and defective sperm tail. We demonstrated that the unique C-terminal sequences found in Gykl1 and Gk2 mediated their targeting to the mitochondrial outer membrane. Furthermore, both Gykl1 and Gk2 could interact with Pld6 (MitoPLD) and induce Pld6 and phosphatidic acid (PA)-dependent mitochondrial clustering in cells. Taken together, our study has revealed previously unsuspected functions of Gyk-like proteins in spermiogenesis, providing new insight into the potential mechanisms that lead to spermatozoa dysfunction and male infertility.

We perform a three-dimensional (3D) global simulation of Earth's magnetosphere with kinetic reconnection physics to study the flux transfer events (FTEs) and dayside magnetic reconnection with the recently developed magnetohydrodynamics with embedded particle-in-cell model (MHD-EPIC). During the one-hour long simulation, the FTEs are generated quasi-periodically near the subsolar point and move toward the poles. We find the magnetic field signature of FTEs at their early formation stage is similar to a `crater FTE', which is characterized by a magnetic field strength dip at the FTE center. After the FTE core field grows to a significant value, it becomes an FTE with typical flux rope structure. When an FTE moves across the cusp, reconnection between the FTE field lines and the cusp field lines can dissipate the FTE. The kinetic features are also captured by our model. A crescent electron phase space distribution is found near the reconnection site. A similar distribution is found for ions at the location where the Larmor electric field appears. The lower hybrid drift instability (LHDI) along the current sheet direction also arises at the interface of magnetosheath and magnetosphere plasma. The LHDI electric field is about 8 mV/m and its dominant wavelength relative to the electron gyroradius agrees reasonably with MMS observations.

Purpose – This paper aims to solve the problem that the changing of groove size and assembly gap would affect the precision of the multi-pass path planning and the welding quality and realize the automatic welding of a thick plate. Design/methodology/approach – First, a double-sided double arc welding (DSAW) system with a self-designed passive vision sensor was established, then the image of the groove was captured and the characteristic parameters of groove were extracted by image processing. According to the welding parameters and the extracted geometry size, multi-pass path planning was executed by the DSAW system. Findings – A DSAW system with a self-designed passive vision sensor was established which can realize the welding thick plate by double-sided double arc by two robots. The clear welding image of the groove was acquired, and an available image processing algorithm was proposed to accurately extract the characteristic parameters of the groove. According to the welding parameters and the extracted geometry size, multi-pass path planning can be executed by the DSAW system automatically. Originality/value – Gas metal arc welding is used for root welding and filler passes in DSAW. Multi-pass path planning for thick plate by Double-sided Double Arc Welding (DSAW) based on vision sensor was proposed.

The welding with weaving has been used widely to obtain better weld quality by avoiding lack of side wall fusion and improve the weld efficiency by obtaining the wide weld bead. But the effect of weave frequency and weave amplitude on the temperature field is not clear. In the present paper, a coordinate transformation method is put forward to simulate the weave welding process. The temperature distribution during the welding with weaving under different weave parameters are compared and discussed. Comparison between experimental and simulation results reveals a good agreement. The peak temperature and the average temperature in weld seam center decreased due to the increasing of the weave amplitude and weave frequency. But the weave frequency has less effect on the average temperature.

A first-principles investigation of the interplay of S and P and their role on the cleavage rupture of γ-Ni/γ′-Ni 3 Al interface is conducted. Trace elements S and P can coexist in the γ-Ni/γ′-Ni 3 Al interfacial region and their site preferences are scarcely changed by another heterogeneous element. S and P in duplex doping systems tend to simultaneously replace for a Ni and occupy an octahedral interstice adjacent to substituted sub-lattice site to form a doping atom pair, but the interaction between S-doping and P-doping varies with their distributions along or across the interfacial layer. The cleavage fracture of duplex doping interfaces generally occurs in the region between S-doped and P-doped atomic layers, and an extra heterogeneous dopant will further aggravate S- or P-induced embrittlement. It is revealed a strong repulsive interaction between P-doping and S-doping is responsible for the descent of cleavage fracture strengths caused by extra heterogeneous dopants.

α-Fe2O3 has been regarded as a promising candidate as anode materials for high energy-density lithium-ion batteries, because of its high capacity, low cost and environmental affinity. A facile hydrothermal route has been developed to synthesize monocrystalline microporous and mesoporous α-Fe2O3 particles by using anions Cl− and F− as pore-formation additives in precursor solution, respectively. Electrochemical investigation indicates that the mesoporous α-Fe2O3 particles display higher cyclic stabilities and capacity retentions than the microporous α-Fe2O3 particles at different current densities, although their sizes are in micrometer range, which indicate that the mesoporous α-Fe2O3 particles are promising anode candidate for high energy-density lithium-ion batteries. Furthermore, this facile hydrothermal route using anion Cl− or F− as pore-formation additives may be extended to synthesis of other porous metal oxides.

A new technology of double-sided arc welding (DSAW) in which gas metal arc welding (GMAW) is employed for root welding and filler passes was proposed in this paper. The realized master–slave mode, dual-robot collaboration provides the asymmetric and symmetric welding for root welding and filler passes, respectively, by two robots from both sides of the thick plate. Then, the multi-pass path planning was put forward, and Roboguide was used to verify the feasibility of the planning. Finally, welding experiment was conducted. The results indicate that the good comprehensive properties in tensile strength, bend property, impact toughness, and hardness were obtained. This new technology can realize no back chipping for thick plate welding. Furthermore, it has the potential advantages for the implementation of automatic welding for thick plate.

Arc sensing plays a significant role in the control and monitoring of welding quality for aluminum alloy pulsed gas touch argon welding (GTAW). A method for online quality monitoring based on adaptive boosting algorithm is proposed through the analysis of acquired arc voltage signal. Two feature extraction algorithms were developed in time domain and frequency domain respectively to extract six statistic characteristic parameters before removing the pulse interference using the wavelet packet transform (WPT), based on which the Adaboost classification model is successfully established to evaluate and classify the welding quality into two classes and the classified accuracy of the model is as high as 98.81%. The Adaboost algorithm has been verified to be feasible in the online evaluation of welding quality.