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Civil engineering works such as buildings and infrastructure are the carriers of human civilization. They are, however, also the origins of various types of disasters, which are referred to in this paper as civil engineering disasters. This paper presents the concept of civil engineering disasters, their characteristics, classification, causes, and mitigation technologies. Civil engineering disasters are caused primarily by civil engineering defects, which are usually attributed to improper selection of construction site, hazard assessment, design and construction, occupancy, and maintenance. From this viewpoint, many so-called natural disasters such as earthquakes, strong winds, floods, landslides, and debris flows are substantially due to civil engineering defects rather than the actual natural hazards. Civil engineering disasters occur frequently and globally and are the most closely related to human beings among all disasters. This paper emphasizes that such disasters can be mitigated mainly through civil engineering measures, and outlines the related objectives and scientific and technological challenges.

The speedy development of UAV (Unmanned Aerial Vehicle) has provided more data choices for crop yield estimation. In most cases, spectral information derived from multispectral or hyperspectral images is used alone for yield estimation, while variables that contain spatial information such as textural measures were not considered. As UAV can acquire images with spatial resolution at centimeter-level, which contain rich spatial information of observed objects, the test of textural measures in improving yield estimation becomes possible. In this study, UAV-based hyperspectral images of rice in the east of China were acquired in 2017, 2018 and 2019 three consecutive year during rice growing seasons. Eight gray level co-occurrence matrix (GLCM) based texture measures were derived, and all two band combinations of these textural measures as well as spectral reflectance in three types (normalized type, differential type and simple ratio type) were calculated to developing textural and spectral index. Grain yield estimation models were established using spectral indices alone and spectral indices combining textural measures, respectively. The results show that models based on spectral indices combining textural measures all performed better than these using spectral indices alone, with coefficient of determination R2 of the best model greater than 0.8, RMSE (Root Mean Square Error) of 0.421 Mg ha−1 and MAPE (Mean Absolute Percentage Error) of 4.66% for calibration results, and 0.521 Mg ha−1 and 6.63% for validation results. Meanwhile, spectral indices combining textural measures can adjust the problems of overestimation and underestimation in models developed with spectral indices alone. This kind of improvement is especially obvious when grain yield is below 5.0 Mg ha−1 or above 8.0 Mg ha−1. Besides, the estimation accuracy of the model based on spectral index combining textural measure at the booting stage was equivalent to the model based on spectral indices at the booting and heading stages, indicating that textural measures may be helpful in monitoring grain yield at an earlier stage.

A facile method was used to prepare Pd-doped CuO nanoflowers with various doping concentrations. The samples were characterized through X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectrometer (ICP-AES), and Brunauer – Emmett – Teller (BET) specific surface area analysis. The responses (Rg/Ra or Ra/Rg, where Rg is the resistance in gas, and Ra is the resistance in air) of such sensors exposed to 50 ppm CH4, NO2, C2H5OH, H2S, NH3, and H2 were measured for comparison. For 1.25 wt% Pd-doped CuO nanoflowers, the response (Rg/Ra) to 50 ppm H2S was 123.4 at 80 °C, which was significantly higher than that of pure CuO (Rg/Ra = 15.7). Furthermore, excellent stability and repeatability of the gas sensor were also demonstrated. The observed results clearly revealed that it is an important and facile approach to detect the H2S at low operating temperature for practical applications.

How to incorporate near-fault directivity effect into the ground motion prediction equations (GMPEs) is an active research topic in recent years. Many studies demonstrated that the directivity could amplify the spectral accelerations (S a) in a range close to the pulse period (T p). This study intends to propose a new empirical narrowband model for including such effects. The ratio of the S a from the original ground motions to the S a from the residual ground motions is employed to quantify this amplification effects, under the assumption that the S a from the residual ground motions are well predicted by the non-directivity-included GMPEs. Differing from previous models that suggested the amplified S a arise in a smooth bell-shaped pattern, the proposed model assumes that the peak amplification occurs as a plateau in the intermediate range. This plateau, having a constant ordinate of about 3.31, starts and ends at the period of 0.75 and 1.09 times the T p, respectively; while in the other ranges the amplification decreases away from the two sides of this plateau. To further simplify the proposed model, two additional controlling periods are derived to determine the period range with significant amplification effects. Then the proposed model is expressed in the form of a piecewise function comprising five line segments. Finally, it is concluded that the non-directivity-included GMPEs, when multiplying the proposed model, can reasonably approximate the S a of the original ground motions in the statistical sense within the T p-related range.

Many earthquakes have indicated that the mainshock-damaged structures may be more vulnerable to severe damage and collapse during the subsequent aftershocks. This manuscript presents a framework for the vulnerability assessment of structure under the mainshock-aftershock sequences. In this framework, the engineering demand parameter (EDP) which can more effectively characterized the additional damage of structure induced by aftershock, and the intensity measure (IM) having the higher correlation with the additional damage of structure are selected and used. The versatility of the proposed framework is demonstrated on a case-study reinforced concrete (RC) frame structure with 5 stories. The influences of aftershocks on the fragility of structure are studied for different limit states. The effects of aftershocks on the fragility of structure are more obvious for the case that mainshock fragility changes from 30% to 60%, and the maximum influence of aftershock can exceed 15%. The results in this study can be used to evaluate the vulnerability of structure under the seismic sequence in the pre-earthquake environment.

The development of a powerful numerical model to simulate the fracture behavior of concrete material has long been one of the dominant research areas in earthquake engineering. A reliable model should be able to adequately represent the discontinuous characteristics of cracks and simulate various failure behaviors under complicated loading conditions. In this paper, a numerical formulation, which incorporates a sophisticated rigid-plastic interface constitutive model coupling cohesion softening, contact, friction and shear dilatation into the XFEM, is proposed to describe various crack behaviors of concrete material. An effective numerical integration scheme for accurately assembling the contribution to the weak form on both sides of the discontinuity is introduced. The effectiveness of the proposed method has been assessed by simulating several well-known experimental tests. It is concluded that the numerical method can successfully capture the crack paths and accurately predict the fracture behavior of concrete structures. The influence of mode-II parameters on the mixed-mode fracture behavior is further investigated to better determine these parameters.

Support vector regression (SVR) has unique advantages in system modeling because of the structural risk minimization principle. However, its model generalization ability is subject to excitation signals and kernel parameters. An SVR modeling method excited by sinusoidal signals based on kernel space features is proposed to improve the generalization ability. First, the effect of amplitude of the sinusoidal excitation signals on the generalization ability of SVR model is analyzed. The following conclusions are drawn. The amplitude of the best excitation signal should be in the same order of magnitude as that of actual input signal and not smaller than the amplitude of the actual input signal. Second, based on the considered SVR modeling problem in the classification problem, the kernel space feature named inter-cluster distance (ICD) is employed to determine a more effective searching range of the kernel parameter. Simulation experiments results show less training time and the superior generalization ability of the proposed method. Thus, the proposed method can be used as a guide to select the sinusoidal excitation signals and kernels parameters of SVR models. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

In this paper, a novel decentralized control for a dynamic voltage restorer is proposed to deal with its captivity by improving the voltage quality of loads. The proposed technique controls the magnitude and the phase angle of the injected voltage to accomplish low-voltage ride-through based on the instantaneous calculations of voltages and currents and the application of elliptical compensation properly demonstrated at first. A set of generalized equations based on symmetric-sequence components are represented, aiming to separately control active and reactive powers with two individually adaptable parameters. Moreover, this approach can also describe a theoretical methodology by regulating the status parameters so that the multiple alternatives can be provided. The two parameters are an external voltage contribution of this work utilized to raise and equalize the phase voltage for a particular purpose of positive- and negative-sequence injected powers. Furthermore, a control algorithm for reference generators that provide flexible voltage support is proposed simultaneously to improve ride-through ability. Results of the simulation in the MATLAB indicate that the proposed control strategies can compensate voltage sags in a considerable short-time period. Finally, the laboratory test is performed to verify the effectiveness of the proposed approach that preserves flexible controllability.

Over the past several decades, the frequency of antibacterial resistance in hospitals, including multidrug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC. We approached this through the design, synthesis, and biological evaluation of novel hydroxamic acid LpxC inhibitors, exemplified by 1, where cytotoxicity against mammalian cell lines was reduced, solubility and plasma-protein binding were improved while retaining potent anti-pseudomonal activity in vitro and in vivo.

The current study examined the psychometric properties of the Chinese version of Prosocial Tendencies Measure (PTM-C) with Chinese adolescents in Hong Kong. Data were derived from 1976 students (Mean age = 14.6 years; 50.1% female) from 17 secondary schools. An exploratory factor analysis was applied first to find out the factor patterns, and then a confirmatory factor analysis was conducted to verify model structures obtained from the exploratory factor analysis. After that, two measurement invariance tests were used to test the construct stability across gender and educational levels. Internal consistency was examined by performing Cronbach’s alpha test. Associations between volunteering and prosocial behaviors and gender differences were also analyzed for concurrent validity examination. Results yielded partial support for the reliability and validity of PTM-C to use with Chinese adolescents in Hong Kong. Differences in findings and suggestions for further revision of PTM-C were discussed.

The main objective of this study is to assess the accuracy and applicability of static pushover analysis (POA). The POA is widely used to estimate the structural seismic response due to its simplicity. However, the accuracy of this method still needs to be evaluated due to the inherent limitations in its theory, especially for the evaluation of structural collapse capacity problems. Meanwhile, the collapse tests are also lacking to verify the accuracy of POA when it is used to assess the structural collapse capacity. In this paper, the accuracy and applicability of the POA are evaluated through comparison with the dynamic time history analysis (THA) which validated by a ductile RC frame complete collapse shaking table test. The study compared the top displacement, the inter-story drift ratio and the curvature of column ends. It is found that the POA tends to greatly underestimate the structural responses when the structure is severely damaged and close to the collapse state. The errors increase with the development of structural damage, where the maximum error could reach more than 60%. The POA may provide incorrect judgement on the occurrence of collapse. Prudent use of POA is needed while assessing the structural seismic collapse capacity.

This study proposes a Green’s function, an essential representation of water-saturated ground under moving excitation, to simulate ground borne vibration from trains. First, general solutions to the governing equations of poroelastic medium are derived by means of integral transform. Secondly, the transmission and reflection matrix approach is used to formulate the relationship between displacement and stress of the stratified ground, which results in the matrix of the Green’s function. Then the Green’s function is combined into a train-track-ground model, and is verified by typical examples and a field test. Additional simulations show that the computed ground vibration attenuates faster in the immediate vicinity of the track than in the surrounding area. The wavelength of wheel-rail unevenness has a notable effect on computed displacement and pore pressure. The variation of vibration intensity with the depth of ground is significantly influenced by the layering of the strata soil. When the train speed is equal to the velocity of the Rayleigh wave, the Mach cone appears in the simulated wave field. The proposed Green’s function is an appropriate representation for a layered ground with shallow ground water table, and will be helpful to understand the dynamic responses of the ground to complicated moving excitation.

Purpose The aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes—refractory anemia with excess of blasts (MDS-RAEB). Methods The current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens. Results A total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2–21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at

Upregulated expression of efflux pumps, lpxC target mutations, LpxC protein overexpression, and mutations in fabG were previously shown to mediate single-step resistance to the LpxC inhibitor CHIR-090 in P. aeruginosa. Single-step selection experiments using three recently described LpxC inhibitors (compounds 2, 3, and 4) and mutant characterization showed that these mechanisms affect susceptibility to additional novel LpxC inhibitors. Serial passaging of P. aeruginosa wild-type and efflux pump-defective strains using the LpxC inhibitor CHIR-090 or compound 1 generated substantial shifts in susceptibility and underscored the interplay of efflux and nonefflux mechanisms. Whole-genome sequencing of CHIR-090 passage mutants identified efflux pump overexpression, fabG mutations, and novel mutations in fabF1 and in PA4465 as determinants of reduced susceptibility. Two new lpxC mutations, encoding A214V and G208S, that reduce susceptibility to certain LpxC inhibitors were identified in these studies, and we show that these and other target mutations differentially affect different LpxC inhibitor scaffolds. Lastly, the combination of target alteration (LpxC(A214V)) and upregulated expression of LpxC was shown to be tolerated in P. aeruginosa and could mediate significant decreases in susceptibility.

Human amniotic epithelial cells (hAECs), as pluripotent stem cells, have characteristics of immune privilege and great clinical potential. Here, we produced hAECs membrane consisting of single-layer hAECs and basal membrane (BM) of human amniotic membrane (hAM). In conventional methods, hAECs were isolated from hAM by repeated trypsin digestion. In this study, collagenase I and cell scraper were used to remove human amniotic mesenchymal stem cells (hAMSCs) from hAM and hAECs-only membranes were produced. These hAECs on the membranes were evaluated by surface biomarkers including epithelial cell adhesion molecule (EpCAM), stage-specific embryonic antigen 4 (SSEA4) and endoglin (CD105), transcriptional level of biomarkers including POU class 5 homeobox 1 (OCT4), sex determining region Y-box 2 (SOX2), fibroblast growth factor 4 (FGF4), immunofluorescence of cytokeratin-8 (CK-8), alpha smooth muscle actin (α-SMA) and collagen type I alpha 1 chain (ColA1). Finally, the hAECs membrane were transplanted on skin-removed mice to evaluate its effect on wound healing. In comparison to the hAECs isolated by the conventional methods, the cells isolated by this proposed method had higher purity of hAECs, expressed higher in pluripotency related genes, and maintained an epithelium construction in a long-term culture. In mice application, the hAECs membrane effectively improved the skin wound healing. An efficient method was successfully established to produce hAECs membrane in this work which not only held promise to obtain hAECs in higher purity and quality, but also showed practical clinical potential.

The optic nerve conveys information about the outside world from the retina to multiple subcortical relay centers. Until recently, the optic nerve was widely believed to be incapable of re-growing if injured, with dire consequences for victims of traumatic, ischemic, or neurodegenerative diseases of this pathway. Over the past 10-20 years, research from our lab and others has made considerable progress in defining factors that normally suppress axon regeneration and the ability of retinal ganglion cells, the projection neurons of the retina, to survive after nerve injury. Here we describe research from our lab on the role of inflammation-derived growth factors, suppression of inter-cellular signals among diverse retinal cell types, and combinatorial therapies, along with related studies from other labs, that enable animals with optic nerve injury to regenerate damaged retinal axons back to the brain. These studies raise the possibility that vision might one day be restored to people with optic nerve damage.

In this study, from experiments and theoretical calculation, we reported that Ti

The problem of characterizing voltage fluctuation is addressed as a means of the sag/swell identification in electricity networks based on the particle swarm optimization (PSO) in this paper. A new objective function of optimization algorithm to identify the voltage sags caused by short circuit fault(s) is obtained to describe the depth and types of sag/swell. Due to only a few sampling points are used in the objective function, the parameters of the ellipse could be recognized in subcycle to classify the sag. The results show that proposed method can identify not only the single stage sag but also the multistage sag within a cycle. MATLAB-based simulation results are discussed in detail to support the concept and validate the feasibility of proposed method.

The anti-cancer agent Indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which Indisulam mediates DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-Indisulam-RBM39(RRM2) complex structure to 2.3 Å. DCAF15 has a novel topology which embraces the RBM39(RRM2) domain largely via nonpolar interactions, and Indisulam binds between DCAF15 and RBM39(RRM2) and coordinates additional interactions between the two proteins. Studies with RBM39 point mutants and Indisulam analogs validated the structural model and defined the RBM39 alpha-helical degron motif. The degron is found only in RBM23 and RBM39 and only these proteins were detectably downregulated in Indisulam-treated HCT116 cells. This work further explains how Indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade novel targets.

The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.3 A. DCAF15 has a distinct topology that embraces the RBM39(RRM2) domain largely via non-polar interactions, and indisulam binds between DCAF15 and RBM39(RRM2), coordinating additional interactions between the two proteins. Studies with RBM39 point mutants and indisulam analogs validated the structural model and defined the RBM39 α-helical degron motif. The degron is found only in RBM23 and RBM39, and only these proteins were detectably downregulated in indisulam-treated HCT116 cells. This work further explains how indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade additional targets.

Cross validation (CV) is widely used to find the optimal parameters of the support vector regression (SVR) model. Regarding the conventional CV method, the optimal model parameters may be affected when the training set is randomly split into k disjoint folds. In the paper, an efficient CV based on center distance in kernel space is presented. Data splitting is based on the distance between the sample and the center point in the kernel space. Simulation experiments results show that the proposed CV method makes the selection of optimal model parameters more reasonable and improves the generalization ability of SVR model.

The advantages and promoting applications of the microgrids community (MGC) allows for a critical step being taken toward a smart grid. An energy management strategy (EMS) is essential to intelligently coordinate the operations of the MGC. This paper presents a multi-time-scale EMS considering battery operational modes for grid-connected MGCs. The proposed strategy consists of two modules: day-ahead integrated optimization and realtime distributed compensation. The first module aims to minimize the operational cost of the MGC considering battery free-overcharging protecting. This problem is solved by the mixed integer linear programming (MILP) simulating two charging/discharging modes: limited-current mode and constant-voltage mode. The second module is installed in local MGs to correct the optimizing deviations of the dayahead static scheduling, which are caused by predicting errors of renewable energy and loads. The main contribution of this work is integrating the advantages of global optimization of the centralized method and the fast computing speed of the distributed method. Experimental results prove the proposed EMS is feasible and effective. The computing time at each updating step is reduced by 75% on average, which has the potential to be adopted in engineering.

GRAPHICAL ABSTRACTSUMMARYA hallmark of chronic hepatitis B virus (CHB) infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A novel small molecule RG7834 has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase protein 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential novel host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identified novel factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients.

Timely and accurate prediction of rice yield information is closely related to the people’s livelihood, which has been attached great importance by all levels of government. Satellite remote sensing provides the possibility for large-scale crop yield estimation, but they are usually limited by spatial and spectral resolution. Unmanned Aerial Vehicles (UAV) remote sensing with hyperspectral sensors can obtain high spatial-temporal resolution and hyperspectral images on demand. Generally, time-series Vegetation Indices (VIs) are used for estimating grain yield. But multi-day vegetation indices may be affected by different background and illumination condition, so the differences between vegetation indices may include the effects induced from external condition, which will pose a negative effect on the accuracy of crop yield estimation. Therefore, in this study, the relative vegetation index and relative yield were proposed and used to estimate rice yield at pixel scale. And the optimal growth stages for crop yield estimation would also be determined. Hyperspectral images of critical rice growth stages at tillering stage, jointing stage, booting stage, heading stage, filling stage, ripening stage were obtained from July 28 to November 24 in 2017. Firstly, all possible two-band combinations of discrete channels from 500nm to 900nm was used to create Relative Normalized Difference Vegetation Index (RNDVI). Then the best RNDVI at different growth stages were determined for rice yield estimation. Finally, different combinations of growth stages were tested to obtain the optimal combinations for yield estimation. These models were validated at pixel scale using the measured yields. The result shows that four-growth-stage model with RNDVI [635, 784] at tillering stage, RNDVI [744,807] at jointing stage, RNDVI [712,784] at booting stage, RNDVI [736,816] at heading stage with the multiple linear regression function gain a higher R2 (0.74) and lower RMSE (248.97kg/ha). The mean absolute percentage error of estimated rice yield of 4.31%. Results shows that the yield estimations at pixel scale with relative vegetation indices were acceptable. In the study, a yield estimation method with relative vegetation indices is proposed and the optimal growth stage combinations for rice yield estimation were determined. This study explores the possibility of yield estimation at pixel scale using hyperspectral images from UAV platform, which will further improve the method system for remote sensing of yield estimation.

Summary: A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A small molecule, RG7834, has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase proteins 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identify additional factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients. : Hyrina et al. employ a non-biased functional CRISPR screening approach to identify host factors regulating HBsAg expression as well as those targeted by RG7834, a HBsAg inhibitor. The screen highlighted over 60 genes and identified a mechanism by which ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing. Keywords: HBV, HBsAg, CRISPR, genome-wide screen, RG7834, ZCCHC14, TENT4B, RNA tailing

Background Adipose-derived mesenchymal stem cells (ADMSCs) are considered an efficient and important candidate for male infertility treatment because they contain pluripotent stem cells, which can differentiate into all cells from three germ layers. However, the efficient generation of male germ-like cell (MGLCs) is one of the key issues, and little is known about the mechanisms underlying generation of MGLCs. Herein, we attempt to improve the efficient generation of MGLCs derived during co-culturing of rat ADMSCs with SCs under retinoic acid (RA) and testosterone (T) treatment. Methods ADMSCs isolated from male SD rat were induced into generation of MGLCs by using respective methods in vitro. Transwell insert system was used for co-culturing. Busulfan-induced non-obstructive azoospermia rat mode was used to evaluate spermatogenic recovery ability of treated ADMSCs. Besides, the relative gene expression level was detected by reverse transcription PCR, quantitative RT-PCR. The relative protein expression level was detected by western blot (WB) and immunostaining analysis. Results The results showed that ADMSCs co-cultured with TM4 cells under RA and T induction enhanced the formation of bigger and tightly packed MGLCs feature colonies in vitro. Moreover, the expression of male germ cell-related markers (Oct4, Stella, Ddx4, Dazl, PGP9.5, Stra8, and ITGα6) is significantly upregulated in TM4 cell-co-cultured ADMSCs in vitro and in busulfan-treated rat testis after injecting TM4 cell-treated ADMSCs for 2 months. Comparatively, the ADMSCs treated by TM4 cell with RA and T exhibited the highest expression of male germ cell-related markers. RA- and T-treated TM4 cell showed fewer dead cells and higher cytokine secretion than untreated groups. The protein expression level of TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways in ADMSCs co-cultured with TM4 cells under RA and T was higher than others. Whereas, downregulation of male germ cell-related marker expression subsequently inhibited the phosphorylation of SMAD2/3, JAK2, STAT3, and AKT. Conclusion These results suggested that TM4 cells could efficiently stimulate in vitro generation of MGLCs during co-culturing of ADMSCs under RA and T treatment. Conclusively, the ADMSCs co-cultured with TM4 cell under RA and T induction stimulate the efficient generation of MGLCs in vitro through activating TGFβ-SMAD2/3, JAK2-STAT3, and AKT pathways. Among them, JAK2-STAT3 and AKT pathways are being first reported to show involvement of in vitro generation of MGLCs during ADMSC co-culturing with SCs. Electronic supplementary material The online version of this article (10.1186/s13287-019-1181-5) contains supplementary material, which is available to authorized users.

Background Embryonic Sertoli cells (eSCs) play an important role in sex determination and in male gonad development which makes them a very useful cell type for therapeutic applications. However, the deriving mechanism of Sertoli cells has been unclear and challenging to create a large number of quality eSCs. Therefore, this study aimed to create the eSCs induced from mouse embryonic stem (mES) cells by regulating defined factors and to explore the relevant regulatory mechanism. Methods Six inducing factors, Sry, Sox9, SF1, WT1, GATA4, and Dmrt1, were respectively transduced into mES cells by lentiviral infection according to the experimental design. The test groups were identified by development stage-specific markers, AMH, Emx2, SF1, and FasL, using flow cytometry. Induced eSCs were determined by FasL and AMH biomarkers under immunofluorescence, immunocytochemistry, and flow cytometry. Moreover, the pluripotency markers, gonad development-related markers, epithelial markers and mesenchymal markers in test groups were transcriptionally determined by qPCR. Results In this study, the co-overexpression of all the six factors effectively produced a large population of eSCs from mES cells in 35 days of culturing. These eSCs were capable of forming tubular-like and ring-like structures with functional performance. The results of flow cytometry indicated that the upregulation of GATA4 and WT1 contributed to the growth of somatic cells in the coelomic epithelium regarded as the main progenitor cells of eSCs. Whereas, SF1 facilitated the development of eSC precursor cells, and Sry and Sox9 promoted the determination of male development. Moreover, the overexpression of Dmrt1 was essential for the maintenance of eSCs and some of their specific surface biomarkers such as FasL. The cellular morphology, biomarker identification, and transcriptomic analysis aided in exploring the regulatory mechanism of deriving eSCs from mES cells. Conclusion Conclusively, we have elucidated a differentiation roadmap of eSCs derived from mES cells with a relevant regulatory mechanism. Through co-overexpression of all these six factors, a large population of eSCs was successfully induced occupying 24% of the whole cell population (1 × 105 cells/cm2). By adopting this approach, a mass of embryonic Sertoli cells can be generated for the purpose of co-culture technique, organ transplantation, gonadal developmental and sex determination researches. Electronic supplementary material The online version of this article (10.1186/s13287-019-1180-6) contains supplementary material, which is available to authorized users.

Lanthanide-doped upconversion nanoparticles capable of converting incident near-infrared (NIR) photons into visible emission have been widely used in light-mediated theranostics due to their advantages of deep-tissue penetration, nonblinking luminescence, high photostability, and excellent biocompatibility. These unique features make them attractive in biosensing, optical imaging, and noninvasive therapy for biomedical applications. In this chapter, we present an overview of recent developments of upconversion nanomaterials for NIR light-mediated theranostics. We give a brief introduction to lanthanide-doped upconversion nanoparticles and discuss their utility as nanoprobes in biological detection, in vivo optical imaging, and biomedical therapy. At the end of the chapter we give a summary on the development and perspectives in this field.

Solution-processed metal-halide perovskites hold great promise in developing next-generation low-cost, high-performance photodetectors. However, the weak absorption of perovskites beyond the near-infrared spectral region posts a stringent limitation on their use for broadband photodetectors. Here, the rational design and synthesis of an upconversion nanoparticles (UCNPs)-perovskite nanotransducer are presented, namely UCNPs@mSiO2 @MAPbX3 (X = Cl, Br, or I), for broadband photon detection spanning from X-rays, UV, to NIR. It is demonstrated that, by in situ crystallization and deliberately tuning the material composition in the lanthanide core and perovskites, the nanotransducers allow for a high stability and show a wide linear response to X-rays of various dose rates, as well as UV/NIR photons of various power densities. The findings provide an opportunity to explore the next-generation broadband photodetectors in the field of high-quality imaging and optoelectronic devices.

A flexible fabric gas sensor for the detection of sub-ppm-level NH3 is reported in this paper. The reduced graphene oxide (rGO)-polyaniline (PANI) nanocomposite was successfully coated on cotton thread via an in situ polymerization technique. The morphology, microstructure and composition were analyzed by field-emission scanning electron microscope, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Furthermore, we have studied the responses of the rGO-PANI nanocomposite-based flexible sensors for the detection of NH3 varying from 1–100 ppm, operated at 22 °C. At the optimized concentration of rGO, the response of these sensors increased by 4–5 times in comparison with the pristine rGO and PANI. These flexible sensors exhibited fast response, remarkable long-term stability, good selectivity and a low detection limit. The sensing mechanism for the high sensing performance has been thoroughly discussed and it is mainly due to the distinctive 1D fiber structure, the formation of a p-p heterojunction between the rGO nanosheets and PANI. The rGO-PANI composite-based fabric sensor with low power consumption is a potential flexible electronic device for the detection of NH3.

A fast repair method is developed for earthquake induced-flexure/shear damage at the bottom of the reinforced concrete (RC) columns. The method is a kind of hybrid jacket that employs a thin stainless steel jacket wrapped around the column and the outside stainless prestressed steel hoops. The prestressed steel hoops provide active confinement for the column and prevent premature buckling of the steel jacket. The stainless steel jacket provides confinement to the core concrete, and, as well as, prevent the prestressed hoops from penetrating the concrete to cause stress loss. A large-scale RC column was damaged during pseudo-static cyclic loads, firstly, and then repaired with this method as experimental validation. The pseudo-static cyclic test results from the original and repaired RC columns were compared for failure mode, hysteresis behavior, strength and stiffness degradation, ductility, energy dissipation, and damage status. The repair method was proved to be effective in restoring the structural behavior of the damaged columns to prevent bridge collapse. The ductility of the repaired specimens was 111.4% that of the original specimen; the lateral force capacity was 113.3% that of the original specimen. This repair method can be used to repair columns with repairable damage as an emergency repair, or construction method for new structures.

Community resilience against major disasters is a multidisciplinary research field that garners an ever-increasing interest worldwide. This paper provides summaries of the discussions held on the subject matter and the research outcomes presented during the Second Resilience Workshop in Nanjing and Shanghai. It, thus, offers a community view of present work and future research directions identified by the workshop participants who hail from Asia - including China, Japan and Korea; Europe and the Americas.

Nucleoside or nucleotide inhibitors are a highly successful class of antivirals due to selectivity, potency, broad coverage, and high barrier to resistance. Nucleosides are the backbone of combination treatments for HIV, hepatitis B virus, and, since the FDA approval of sofosbuvir in 2013, also for hepatitis C virus (HCV). However, many promising nucleotide inhibitors have advanced to clinical trials only to be terminated due to unexpected toxicity. Here we describe the in vitro pharmacology of compound 1, a monophosphate prodrug of a 2′-ethynyluridine developed for the treatment of HCV. Compound 1 inhibits multiple HCV genotypes in vitro (50% effective concentration [EC 50 ], 0.05 to 0.1 μM) with a selectivity index of >300 (50% cytotoxic concentration [CC 50 ], 30 μM in MT-4 cells). The active triphosphate metabolite of compound 1, compound 2, does not inhibit human α, β, or γ DNA polymerases but was a substrate for incorporation by the human mitochondrial RNA polymerase (POLRMT). In dog, the oral administration of compound 1 resulted in elevated serum liver enzymes and microscopic changes in the liver. Transmission electron microscopy showed significant mitochondrial swelling and lipid accumulation in hepatocytes. Gene expression analysis revealed dose-proportional gene signature changes linked to loss of hepatic function and increased mitochondrial dysfunction. The potential of in vivo toxicity through mitochondrial polymerase incorporation by nucleoside analogs has been previously shown. This study shows that even moderate levels of nucleotide analog incorporation by POLRMT increase the risk of in vivo mitochondrial dysfunction. Based on these results, further development of compound 1 as an anti-HCV compound was terminated.

A glassy carbon electrode was modified with a composite consisting of ferrocene imidazolium salts and hydroxy-functionalized graphene in a Nafion matrix. The electrode is shown to facilitate the reduction of oxygen to form the superoxide anion radical. Atomic force microscopy and electrochemical impedance spectroscopy were used to characterize the electrode. The in-situ production of superoxide anion was then studied with an analogue of methyl-Cypridina luciferin (also referred to as Vargulin). As a result, an electrochemiluminescence (ECL) based assay was developed for the improved determination of the activity of the enzyme superoxide dismutase (SOD). Under optimized conditions, the ECL based calibration plot is linear in the 0.5 to 6.5 U·mL−1 SOD activity range, with a 0.2 U·mL−1 detection limit (at a signal-to-noise ratio of 3).

This study investigates the input energy spectra for inelastic single-degree-of-freedom (SDOF) systems under main shock–aftershock sequences. The input energy spectra quantitatively reveal the effects of aftershocks on input energy, which verifies the necessity of incorporating aftershocks in energy-based seismic design. The investigation selects the sequences including one aftershock or two aftershocks respectively, according to the proposed criteria for selecting earthquake records. Then, the input energy for sequences is normalized by mass, m, and expressed in terms of the equivalent velocity, VE, seq. Next, the variation of VE, seqis studied in consideration of the hysteretic models, ductility values, periods of vibration, site conditions, relative intensities of aftershocks and number of aftershocks. The results indicate that the effects of aftershocks on input energy are significant in almost the whole period region. Finally, a simplified expression of input energy is proposed for incorporating aftershocks in energy-based seismic design.

The traditional Kalman filtering-based transfer alignment methods largely depend on prior information for initialisation. However, the initialisation process is hard to fulfil on a moving base. In this paper, a type of inertial measurement vector integration matching for optimisation-based transfer alignment and calibration is proposed to estimate the misalignment between the Master Inertial Navigation System (MINS) and Slave Inertial Navigation System (SINS), and main inertial sensor error parameters of SINS, including bias and scale factor error. In contrast to filter techniques, the proposed method has the capability of self-initialisation and provides a new idea to solve the alignment and calibration problem. No prior information is needed. Moreover, the integration time interval for the matching inertial measurement vector is selected by considering both the observation degree of inertial sensor error parameters and the noise effect. Simulation results demonstrate that the proposed method has faster convergence and is more accurate than Kalman filter techniques.

This study explores the collapse process of a reinforced concrete (RC) frame structure subjected to earthquake shakings, by applying the shaking table test on a three-story, one-bay, 1/5-scaled RC structural model. The frame specimen transformed from an elastic state to a highly nonlinear state, then experienced dynamic instability, and finally collapsed to the ground. The structural responses that have been monitored in the presented test include the specimen’s dynamic properties, displacements, and accelerations. The data collected from this benchmark test program can be used for the verification of existing analytical and numerical simulation methods, especially for cases involving the large displacement and rotation or collapse process simulation of RC frame structures. It is observed from the test that: (1) the frame survived when the maximum story drift ratio and the residual drift ratio reached 12.51% and 9.60% respectively, indicating that the RC frame structure may have a much high ductility capacity; (2) the collapse of the 1st, 2nd, and 3rd stories was due to failure of the plastic hinges at columns; and (3) during the collapse process, the collisions and the damage-induced local oscillation can generate very large horizontal and vertical acceleration responses. More specifically, the collapse of the 1st story was the result of the failure of plastic hinges, caused by seismic excitation, while collapse of the 2nd and 3rd stories resulted from the combined results of plastic hinge failures and punching shear failures in the slab due to impact effects.

To determine the relationship between the polymorphisms of the prostaglandin F2α receptor (PTGFR) and solute carrier organic anion transporter family 2A1 (SLCO2A1) genes and response to latanoprost treatment in Han Chinese patients with glaucoma.89 patients with POAG or OH received latanoprost treatment and intraocular pressure (IOP) data was collected on day 7 and day 30. The rs12093097, rs35586449, rs3753380, and rs3766355 single-nucleotide polymorphisms (SNPs) in the PTGFR gene and rs2370512, rs34550074, and rs4241366 SNPs in the SLCO2A1 gene were analyzed using direct DNA sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The IOP in patients with GG allele of rs4241366 was lower than in patients with GC+CC on day 7 (p = 0.007). The IOP in patients with CC allele of rs3766355 was lower than in patients with CA+AA on day 30 (p = 0.024). Multiple regression analysis demonstrated that even after adjusting for baseline IOP, the rs4241366 in SLCO2A1 gene and the rs3766355 in PTGFR gene correlated with response to latanoprost on day 7 (rs4241366, p = 0.014) and day 30 (rs3766355, p = 0.035), respectively, in Han Chinese patients with glaucoma.An association was found between single nucleotide polymorphisms of the PTGFR and SLCO2A1 genes and the response to latanoprost in Han Chinese patients with glaucoma. These SNPs may be important determinants of differential response to latanoprost.

Pulse‐like ground motions, which are mainly concentrated in near‐fault regions, can induce severe damage on structures. This article presents a simple and effective method used for quantitatively identifying pulse‐like ground motions. First, zero velocity point method is proposed based on the properties of trigonometric functions. This method can reveal the time‐domain characteristics of ground‐motion velocity time history and can be used to detect the potential velocity pulse which is included in corresponding original ground motion. Second, pulse‐like ground motions are classified into two classes: single‐pulse‐like and multi‐pulse‐like ground motions. Further, single‐pulse‐like is divided into significant‐single‐pulse‐like and non‐significant‐single‐pulse‐like, while multi‐pulse‐like is divided into double‐pulse‐like, three‐pulse‐like, and four‐pulse‐like. Third, energy method is adopted to formulate the identification criterion for each type of pulse‐like ground motion. Finally, the energy parameters of the detected potential velocity pulse for a large number of ground motions are calculated, and the proposed identification criteria are applied to identify whether these ground motions are pulse‐like or not. A comparison of the methodology proposed in this study with previous identification methods is presented. Analysis results indicate that the methodology proposed in this study can accurately distinguish pulse‐like and non‐pulse‐like ground motions.

This study is focused on the constant ductility energy factors for bilinear system under the near-fault pulse-like ground motions. The variation of energy factors is studied in consideration of the earthquake magnitude, rupture distance, damping ratios, and post-yield stiffness ratios. The results indicate that the near-fault pulse-like ground motions would increase the energy dissipation of structures. The energy factors are significantly influenced by the earthquake magnitude. The damping ratios have more obvious influences on the energy factors than the post-yield stiffness ratios. A predictive model is proposed for the application of constant ductility energy factors for near-fault pulse-like ground motions.

The interaction between the infill walls and the reinforced concrete (RC) frame members in the progressive collapse process was examined experimentally in this study. Two 1/3 scaled, four-bay, two-story RC frame specimens, one of which was featured without infill walls while the other with infill walls, were tested. The frame specimens were designed in such a way that the center column of the first story was missing, in order to simulate the failure of the structural component due to abnormal loads or design flaws. The frame specimens were quasi-statically pushed downward at the top of center column under displacement control to investigate the progressive collapse mechanism of the RC frames, with a focus on the effects of infill walls. Specifically, the physical quantities and phenomena of great interest in this study include the collapse resistance force and mechanism, strain variation and crack development in structural components, and local and global failure modes of the frames. The test results showed that the infill walls can provide alternative load paths for transferring the loads originally only supported by the beams, and thus, improve the collapse resistance capacity of the RC frame. The infill walls, however, may reduce the ductility of the RC frame and may change the failure mode of the frame. It is concluded that the infill walls may affect (i.e., either improve or impair) the performance of RC frames against progressive collapse in different aspects.

This article makes an attempt to investigate the low-frequency characterizations of pulse-type ground motions through ground motion components instead of original records. A decomposed method based on multi-resolution analysis is introduced in this article. The accuracy and validity of the method is tested in frequency domain, time domain and dynamic response. A dataset of 398 low-frequency components is obtained after the decomposition of 91 typical pulse-type records. A probabilistic model to describe the proportion of low-frequency components in corresponding original ground motions is established. At last, the decomposed method is used to investigate the impulsive characterizations of pulse-type ground motions.

Mesenchymal stem cells (MSCs) have drawn worldwide attention of scientists and clinicians due to their ability to differentiate into other cell lineages, secrete paracrine factors, modulate inflammation and immunity, and also due to the effectiveness of MSCs in treating degenerative diseases. Recent studies have shown that, when cultured in spheroids, MSCs have greater differentiation ability, and increased anti-inflammatory and immunomodulatory capacities compared with traditional two-dimensional (2D) cultures. Furthermore, spheroid MSCs can be used on scale-up productions in clinically relevant manufacturing platforms. Microvesicles (MVs) are small membranous vesicles that can transfer proteins, genetic materials, and lipids to cells. MVs derived from MSCs (MSC-MVs) are not only emerging as potent transfer agents for molecular information, but also are effective in a series of tissue repair and anti-tumor experiments. Therefore, both spheroid MSCs and MSC-MVs have great potential in experimental and clinical applications. In this review, the characteristics, therapeutic applications and potential clinical translational opportunities of spheroid MSCs and MSC-MVs were discussed.

The synthesis of polyfunctionalized aminothioalkenes has been realized via the direct C-H sulfenylation of enaminones and analogous enamines. These cross-coupling reactions have been achieved by simple KIO3 catalysis under aerobic conditions without employing any transition metal catalyst or additional oxidant. The employment of bio-based green solvent ethyl lactate as the reaction medium constitutes another sustainable feature of the present work.

The work presented in this study aimed to investigate the influence of infill walls on the progressive collapse performance of reinforced concrete (RC) frames. An experimental program of a one-third scaled, four-bay by two-story RC frame with full-height infill walls at the second story was conducted. Experimental results indicate that the maximum resistance force and failure mode of the RC frame with full-height infill walls are relevant to the major crack developments in the infill walls. The infill walls behave as equivalent compressive struts during progressive collapse process and can improve the resistance force and initial stiffness but reduce beam ductility and change failure mode of the RC frames. Verification of the test results and material parametric analyses of the test specimen by using finite element (FE) model were conducted to illustrate the factors that influence the behavior of the infilled frame.