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A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreER

SummaryA cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreERT2 transgenic (Tg) mouse employing previously identified hematopoietic stem cell (HSC) enhancer for Runx1, eR1 (+24m). Kinetic analysis of labeled cells after tamoxifen injection and transplantation assays revealed that eR1-driven CreERT2 activity marks dormant adult HSCs which slowly but steadily contribute to unperturbed hematopoiesis. Fetal and child HSCs which are uniformly or intermediately active were also efficiently targeted. Notably, a gene ablation at distinct developmental stages, enabled by this system, resulted in different phenotypes. Similarly, an oncogenic Kras induction at distinct ages caused different spectrums of malignant diseases. These results demonstrate that the eR1-CreERT2 Tg mouse serves as a powerful resource for the analyses of both normal and malignant HSCs at all developmental stages.

It is very difficult to conduct emergency rescue drills for bus fire accidents in a real environment, which not only requires high costs, but may also cause personal injury to the trainees. With the development of computer technology, the emergence of virtual reality technology provides a new practical mode for emergency drills; by simulating events, trainees respond more intuitively in the virtual environment and carry out emergency rescue drills. This article uses three-dimensional virtual simulation technology to analyze and design the architecture of the emergency rescue deduction system for passenger car fire accidents. The deduction system functions are designed in a modular manner, which is convenient for the stability and reliability of the system and is conducive to implementation. It proposes a practical and efficient method for digital drills.

During tea cultivation, diverse agroforestry is an important and established intercropping measure, with most studies concentrating on ecological service provision and economic returns. However, the response of soil nutrients and microbial community structures in long-term tea plantations with diverse agroforestry intercropping systems is poorly understood. In the present field study (2015), three intercropping agroforestry-tea patterns (Osmanthus-Tea (OT), Michelia-Tea (MT), Osmanthus-Michelia-Tea (OMT)) along with a study control (C) were examined in terms of these two knowledge gaps. Results showed that, in terms of tea cultivation, the OMT system is more suitable than the OT and MT systems. The OMT system significantly increased the total nitrogen (TN, 16.4%), total potassium (TK, 10.5%), available nitrogen (AN, 14.2%), available phosphorus (AP, 26.7%) and soil organic matter (SOM, 28.9%). The OMT system increased phylum Firmicutes and Bacteroidetes abundance by 35.8% and 9.6%. In addition, the OMT system enhanced the abundance of class Bacteroidia (99.5%), Erysipelotrichia (96.9%), Clostridia (93.5%) and Actinobacteria (19.6%), respectively. In general, the phylum bacteria Proteobacteria, Firmicutes, Actinobacteria accounted for the largest proportion of bacteria in all three intercropping systems. In this study, the abundance of Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were positively correlated with AN, SOM and TP. The results of the present study will help to develop a better understanding of the benefits imposed by different agroforestry intercropping systems on nutrient dynamics and microbial structural diversity during tea cultivation.

Ecological rice-cropping systems (ERSs) are prosperous rice ecosystems that have a profound influence on global greenhouse (GHG) effects. However, the high variation in research results requires an accurate evaluation of the ERS effects. In this study, three typical ERS modes, rice-crayfish, rice-duck, and rice-fish were selected, and a meta-analysis was conducted using the data of 34 studies to comprehensively evaluate the effects of ERSs on GHG emissions, the global warming potential (GWP), and GHG intensity (GHGI). The results showed that the ERSs reduced CH4 emissions significantly (-12.5%), but increased N2O emissions by 11.3% as compared with traditional rice-cropping systems (TRSs). Further, ERSs have slightly lower GWP, rice yield, and GHGI values (6.5%, 5.5%, and 5.6%, respectively) than TRSs. The rice-crayfish and rice-duck modes significantly alleviated the GWP by 18.0% and 11.1%, respectively, whereas the rice-fish mode enhanced the GWP by 20.8%. Moreover, the rice-duck mode significantly reduced the GHGI by 17.2%, while the ricecrayfish and rice-fish modes increased the GHGI by 9.7% and 8.8%, respectively. Further, the ERSs significantly changed the dissolved oxygen concentration in the flood water as well as the Eh, dissolved organic carbon, and ammonium nitrogen in the soil, wherein the effect sizes of the ERSs on the GHG emissions were significantly correlated with their respective increase. Considering the net ecosystem economic budget and CO2 emissions equivalent/output, ERSs were found to be effective "green technologies". Further, we found that the rice-duck ERS was a good ecological ricecropping system for global warming mitigation. Our study provided new ideas for sustainable agriculture.

The righting mechanism of the traffic road cone automatic launch and retrieval system is installed on the frame. During normal work, the righting mechanism mainly contacts and interacts with the traffic cone by the movement of the vehicle to right or invert road cone. The study used the basic theory of mechanics to design and check the structure of the righting mechanism and carried out parameter design, selection and simulation model check calculation on the linear motor of the control system of the righting mechanism, so as to complete the design and research on automatic launch and retrieval righting mechanism of traffic road cone.

In paddy soil, the root exudates strongly influence the microbial activity and soil organic matter (SOM) mineralisation. However, the stoichiometric regulation of the mineralisation of root exudates and their priming effect on paddy soil remains unclear. Thus, we used manipulative laboratory incubations to measure the mineralisation of root exudates and the subsequent priming effect in paddy soil under different stoichiometric conditions. In this study, root exudates (simulated by 13C-labelled glucose, alanine, and oxalic acid) were added to the paddy soil along with four different amounts of N and P. The addition of simulated root exudates (SREs) enhanced the total CO2 and CH4 emissions. The mineralisation of SREs decreased by 20–45% after the addition of N and P when compared with exclusive SREs application. The addition of N and P inhibited the SREs-derived CH4 emissions when compared with SREs application alone. The mineralisation of soil organic matter (SOM) increased with SREs application, thereby generating a positive priming effect for CO2 and CH4 emissions. However, the priming effect for CO2 and CH4 emissions was reduced with increased amounts of N and P. Furthermore, the addition of SREs with increasing N and P significantly enhanced the microbial SREs-derived C-use efficiency. Structural equation models indicated that NH4+-N and Olsen P negatively influenced the priming effect, whereas the microbial biomass and enzyme stoichiometry positively influenced the priming effect. In conclusion, our data suggest that SREs combined with increasing amounts of N and P could meet microbial stoichiometric demands and regulate microbial activity, which finally inhibited the mineralisation of SREs-C and the priming effect on paddy soil and positively affected C sequestration.

The time–frequency analysis method is applied to the signal processing of mechanical vibration in this paper, in order to analyze and research the rules and characteristics of mechanical vibration. The mechanical is a nonlinear system and mechanical vibration is an unsteady process. Frequency-domain analysis method based on the technology of FFT is insufficient to research on the nonlinear and unsteady system; because, the Fourier transform theory is only suitable for dealing with the linear and time-invariant system. Time–frequency analysis is an effective technology for the processing of unsteady signals. The time–frequency–energy figures obtained from Hilbert–Huang transform and short-time Fourier transform method could show frequency-domain information clearly with the local time-during states, which will describe the dynamic behaviors of the mechanical system accurately. Combining with the characteristics of a mechanical vibration signal, in this paper, the STFT and HHT time–frequency analysis methods are used to compare with analyzing the mechanical vibration signals. Provide the results of signal processing, and compare the advantages and disadvantages of the STFT and HHT time-frequency analysis methods.

An energy-storage buoyancy regulating system is proposed in order to help underwater robot to float upward and dive downward vertically with low energy consumption. Firstly, principle analysis and system design of underwater buoyancy regulating system are carried out based on the principle of accumulator. After that, we analyze the special performance requirements for system components in deep-sea operating environment, carry out model selection and reliability analysis for main system components (accumulator and hydraulic pump) and build the experimental prototype. Finally, based on the experimental prototype that has been built and under the circumstance of simulating the deep-sea pressure, we carry out function and performance experiment of the system according to the experimental method and procedure that have been designed in advance. The results of pressure experiment indicate that the energy-storage buoyancy regulating system can meet the requirements of anticipated performance index.

Deep-sea hydraulic manipulator is the most commonly used operation equipment for executing subsea operations in different applications. The increasing demands on underwater operational ease require the implementation of manipulator system which can maintain similar dynamic performance in different working conditions Considering the variations of seawater properties at different ocean depths, especially high hydrostatic pressure in deep-sea environment will make the kinematic viscosity of oil obviously increased, which has a significant influence on the performance of deep-sea hydraulic manipulator. The viscosity-pressure characteristics of working medium is tested. A detailed nonlinear mathematical model and related simulations considering the significant slender pipelines between valves and actuators due to the increased oil viscosity are conducted to analyze the ambient pressures against varying depths affecting the manipulator performance. The 115MPa online pressure experimental results indicate the joint response characteristics at different ambient pressures, which provides basis for response consistency control of deep-sea hydraulic manipulator.

This paper presents the development of a full ocean depth master-slave hydraulic manipulator system for marine engineering and research in the harsh hadal environment. Three basic modules of the slave arm including a linear cylinder, a single-vane swing cylinder, and a new wrist joint are designed. The electronic system and software are developed then. Laboratory experiments on the single-vane swing cylinder and the new wrist joint were carried out to verify the performance of new joints. Additionally, a 11000 m pressure experiment is conducted, and the results demonstrate that the full ocean depth hydraulic manipulator system works well in the 11000 m environment.

Electromagnetic interference (EMI) is mainly caused by the periodic valve switching in HVdc converter stations. This EMI can result in high-frequency conducted and radiative interference toward the adjacent communication, computer equipment, carrier system, and radio stations. Therefore, a wideband model of a converter system is necessary to predict the characteristics of the EMI source. Methods of modeling are proposed, and the equivalent circuits of the main equipment in ultra-HVdc (UHVDC), including valve section, converter transformer, smoothing reactor, filters, and so on, are developed in this paper. The whole wideband model is simulated by PSCAD/EMTDC. Based on this model, the characteristics of the conducted EMI under normal operation conditions are calculated. Ground-level electric field strength and magnetic field strength in and around a UHVDC converter station are calculated. For validity, a comparison between the simulated and the measured data is conducted.

Due to the wide application of new technologies, such as wind power, photovoltaic power, distributed generation, and smart grid, the new high-voltage direct current transmission technology based on voltage source converter (VSC-HVdc) has gained great advantages over the traditional one. This paper presents a novel method to analyze the radiated electromagnetic disturbance (EMD) of the VSC-HVdc converter system by combining the circuit theory with the electromagnetic theory, considering its structure together with the operational states. The method combines method of moments (MOM) with antenna theory, based on the experimental platform of the VSC-HVdc converter system located in North China Electric Power University. The mechanism of the radiated EMD generated by converter valve is described, and the source of disturbance is measured by a high-resolution probe and a high-performance oscilloscope. The antenna model of the VSC-HVdc converter system is developed, and by applying electric dipole theory, the radiated EMD produced by the three-phase two-level VSC-HVdc converter system is calculated in FEKO, which can conduct MOM simulation. Finally, the proposed method is verified by the comparison between the calculated data and the measured data, and the influencing factors of EMD are discussed.

As square tube type protective device as the object, selected on the basis of the results of the simulation test, design the crossbar and arm structure plan of the six groups of different wall thickness. Through bus rear-ended dangerous goods transport vehicle simulation test way, analyzes the deformation and energy absorption about the bus and six groups of protective device which has different wall thickness. Research results show that the main energy absorption part of square tube type protective device is the arm structure. The optimal design scheme is when the wall thickness of the arm is 4 mm and the wall thickness of the crossbar is 3 mm.

SummaryThe RUNX genes encode transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here, we show that Runx1;Runx3 double-knockout (DKO) mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes such as Fanconi anemia (FA), caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independently of CBFβ, suggesting a nontranscriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes the development of leukemias and other cancers.

The RUNX1/AML1 gene is among the most frequently mutated genes in human leukaemia. However, its association with T-cell acute lymphoblastic leukaemia (T-ALL) remains poorly understood. In order to examine RUNX1 point mutations in T-ALL, we conducted an amplicon-based deep sequencing in 65 Southeast Asian childhood patients and 20 T-ALL cell lines, and detected RUNX1 mutations in 6 patients (9.2%) and 5 cell lines (25%). Interestingly, RUNX1-mutated T-ALL cases seem to constitute a subset of early immature T-ALL that may originate from differentiated T-cells. This result provides a deeper insight into the mechanistic basis for leukaemogenesis.

A greater control performance of underwater slave arm actuator modules could improve the efficiency and accuracy of the whole master-slave manipulator system. In this paper, the development of the 7-function manipulator can be used in 7000m depth is introduced firstly, and then a hierarchical control scheme is researched to control the manipulator system. The information passed to the lower control system is usually only a higher level decision command, so the hydraulic actuators of the slave arm must be capable of following the command to complete complex tasks in different depth rating underwater environment. In order to ensure the operation reliability of the manipulator, the control performance of the hydraulic actuators of the manipulator has been emphatically verified through on-line pressure experiments in this paper, and the results are reported in detail. Meanwhile, more experiments around the manipulator are researched in this paper.

RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1+/− hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1+/− cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1+/+ cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.

The hallmark of vertebrate definitive hematopoiesis is the establishment of the hematopoietic stem/progenitor cell (HSPC) pool during embryogenesis. This process involves a defined ontogenic switching of HSPCs in successive hematopoietic compartments and is evolutionarily conserved from teleost fish to human. In zebrafish, HSPCs originate from the ventral wall of the dorsal aorta (VDA), from which they subsequently mobilize to an intermediate hematopoietic site known as the caudal hematopoietic tissue (CHT) and finally colonize the kidney for adult hematopoiesis. Despite substantial understanding of the ontogeny of HSPCs, the molecular basis governing migration, colonization and maintenance of HSPCs remains to be explored fully. Here, we report the isolation and characterization of two zebrafish mutants, rumbahkz1 and sambahkz2, that are defective in generating definitive hematopoiesis. We find that HSPC initiation in the VDA and subsequent homing to the CHT are not affected in these two mutants. However, the further development of HSPCs in the CHT is compromised in both mutants. Positional cloning reveals that Rumba is a novel nuclear C2H2 zinc-finger factor with unknown function and samba encodes an evolutionarily conserved protein that is homologous to human augmin complex subunit 3 (HAUS3). Furthermore, we show that these two factors independently regulate cell cycle progression of HSPCs and are cell autonomously required for HPSC development in the CHT. Our study identifies Rumba and Haus3 as two essential regulators of HSPC maintenance during zebrafish fetal hematopoiesis.

Deep-sea master-slave hydraulic manipulator is among most commonly tools equipped on remotely-operated vehicles or human occupied vehicles. The design and realization of a 7-Function master-slave hydraulic manipulator can be used in 7000 meters depth is proposed. Linear actuator, rotary actuator and cycloid motor are the three basic modules of the slave arm. A double-screw-pair swing rotary actuator is designed as the rotary actuator, which realized rotary driving, multi-path oil and electric cable passing through and rotary angle measuring. Based on the reliable running experiments on land, a pressure experiment system to test the manipulator's index of 7000m depth is proposed. In the experiment system, the master controller with the whole system's power supply and experiment monitor are placed outside of the pressure cabin. And the slave arm, slave controller, hydraulic system, underwater light and cameras are inside the cabin. The pressure experimenting process is described in detail. Also, during the exciting experiment, some abjective things were also present, such as the rotary actuator rotating slow even stop rotating in high pressure environment. Complementary experiments aiming at problem arose in the whole system testing had to be done lately. The whole system's and complementary experiment show that the manipulator satisfy 7000m design depth index.

Myelopoiesis is the process of producing all types of myeloid cells including monocytes/macrophages and granulocytes. Myeloid cells are known to manifest a wide spectrum of activities such as immune surveillance and tissue remodeling. Irregularities in myeloid cell development and their function are known to associate with the onset and the progression of a variety of human disorders such as leukemia. In the past decades, extensive studies have been carried out in various model organisms to elucidate the molecular mechanisms underlying myelopoiesis with the hope that these efforts will yield knowledge translatable into therapies for related diseases. Zebrafish has recently emerged as a prominent animal model for studying myelopoiesis, especially during early embryogenesis, largely owing to its unique properties such as transparent embryonic body and external development. This review introduces the methodologies used in zebrafish research and focuses on the recent research progresses of zebrafish myelopoiesis.

Hematopoiesis is a complex process which gives rise to all blood lineages in the course of an organism's lifespan. However, the underlying molecular mechanism governing this process is not fully understood. Here we report the isolation and detailed study of a newly identified zebrafish ugly duckling (Udu) mutant allele, Udusq1. We show that loss-of-function mutation in the udu gene disrupts primitive erythroid cell proliferation and differentiation in a cell-autonomous manner, resulting in red blood cell (RBC) hypoplasia. Positional cloning reveals that the Udu gene encodes a novel factor that contains 2 paired amphipathic α-helix–like (PAH-L) repeats and a putative SANT-L (SW13, ADA2, N-Cor, and TFIIIB–like) domain. We further show that the Udu protein is predominantly localized in the nucleus and deletion of the putative SANT-L domain abolishes its function. Our study indicates that the Udu protein is very likely to function as a transcription modulator essential for the proliferation and differentiation of erythroid lineage.

The stem cell leukemia (SCL) gene encodes a basic helix-loop-helix transcription factor and is essential for embryonic angiogenesis, hematopoietic stem cell specification, and erythrocyte maturation. Here, we report the isolation and characterization of the zebrafish scl promoter. We show that a 5-kilobase (kb) genomic fragment immediately upstream of the translation start site is capable of targeting the enhanced green fluorescence protein (EGFP) expression to the anterior and posterior lateral mesoderm where the endogenous scl normally expresses. Detailed analysis of the stable transgenic fish reveals that this 5-kb upstream sequence is sufficient to direct the EGFP transcription to the brain, spinal cord, and hematopoietic-endothelial progenitors, possibly the hemangioblast, but not primitive erythrocyte, suggesting that the zebrafish scl transcription in hematopoietic-endothelial progenitors and erythrocyte is regulated by distinct cis element(s). Our study has defined the cis regulatory element(s) for zebrafish scl expression in the brain, spinal cord, and hematopoietic-endothelial progenitors and established a valuable transgenic line Tg(5'5kbscl:EGFP) for studying hematopoietic lineage development.