N6-methyladenosine (m6A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 ...intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m6A-dependent manner. Conditional ablation of Mettl3 in CD4+CD8+ double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m6A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m6A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer.
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•Mettl3-dependent m6A methylation plays a key role in iNKT cell development•A comprehensive m6A landscape of low-input iNKT cells is established by m6A-LACE-seq•Mettl3 deficiency disrupts iNKT cell-related gene network in an m6A-dependent manner•The Mettl3-m6A-Creb1 axis is critical for sustaining iNKT cell differentiation and function
You et al. demonstrate that Mettl3 is essential for regulating iNKT cell proliferation, differentiation, and melanoma resistance. The study highlights the critical role of Mettl3-dependent m6A modification in controlling iNKT cell-related gene expression, particularly in maintaining the stability of Creb1 and c-Myc transcripts.
Field practice is an important part of training geography research talents. However, traditional teaching methods may not adequately manage, share and implement instruction resources and thus may ...limit the instructor's ability to conduct field instruction. A possible answer is found in the rapid development of computer‐assisted instruction (CAI), a new teaching mode for the Information Age. A “virtual field trip” is an amalgam of Internet and multimedia techniques with great potential for geography field instruction, as it can arouse students' enthusiasm and immerse them in learning. However, limited by available technology, virtual field trips have disadvantages in terms of content presentation, data organisation, and loss or inadequate representation of spatial information. To overcome the above shortcomings, a map‐based, spatially correlated design method was proposed for a CAI system in geography. By integrating spatial information technology (Geographic Information System, Global Positioning System, remote sensing, etc) and information delivery methods (web services, databases, etc), a WebGIS‐based teaching assistant system for geography field practice (TASGFP) was established, realising an effective spatial management scheme and forming a shared platform for instruction material. Its efficiency was verified through the actual application, although there remains room for improvement. Nevertheless, the TASGFP stands as an effective CAI tool in geography instruction.
The chemical industry poses a potential security risk to factory personnel and neighboring residents. In order to mitigate prospective damage, a synthetic method must be developed for an emergency ...response. With the development of environmental numeric simulation models, model integration methods, and modern information technology, many Decision Support Systems (DSSs) have been established. However, existing systems still have limitations, in terms of synthetic simulation and network interoperation. In order to resolve these limitations, the matured simulation model for chemical accidents was integrated into the WEB Geographic Information System (WEBGIS) platform. The complete workflow of the emergency response, including raw data (meteorology information, and accident information) management, numeric simulation of different kinds of accidents, environmental impact assessments, and representation of the simulation results were achieved. This allowed comprehensive and real-time simulation of acute accidents in the chemical industry. The main contribution of this paper is that an organizational mechanism of the model set, based on the accident type and pollutant substance; a scheduling mechanism for the parallel processing of multi-accident-type, multi-accident-substance, and multi-simulation-model; and finally a presentation method for scalar and vector data on the web browser on the integration of a WEB Geographic Information System (WEBGIS) platform. The outcomes demonstrated that this method could provide effective support for deciding emergency responses of acute chemical accidents.
N
-methyladenosine (m
A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 ...intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m
A-dependent manner. Conditional ablation of Mettl3 in CD4
CD8
double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m
A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m
A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer.
True random number generators (TRNGs) play an important role in encryption systems. In this brief, a novel method of generating true random numbers on a field-programmable gate array (FPGA) is ...proposed based on the random jitter of a multi-stage feedback ring oscillator (MSFRO) as the entropy source. Based on the traditional ring oscillator, a multi-stage feedback structure is added to enlarge the range of clock jitter, and improve the frequency of clock sampling and the randomness of the entropy source. Different from the traditional clock sampling structure, we use the clock jitter signal generated by the MSFRO to sample the clock signal generated by the phase-locked loop (PLL) of the FPGA. The obtained output value is operated by XOR to reduce the deviation of the output value and improve its randomness. The TRNG is implemented in Xilinx Virtex-6 FPGA, which has low hardware resource consumption and high throughput. The entropy source classification, hardware resources and throughput are compared with those of existing TRNGs. The results showed that the proposed TRNG only consumed 24 LUTs and 2 DFFs. Compared with other TRNGs, this design has very low hardware resource consumption and its throughput is up to 290 Mbps. The random bit sequence generated by this TRNG passes the NIST SP800-22 test and the NIST SP800-90B test.
This paper proposes a novel dc-link voltage regulation (DCVR) strategy for the series-series compensated wireless motor (SSWM) system. The steady-state voltage control is presented to optimize the ...system efficiency and the feedforward voltage boost control is proposed to improve system resilience. The rated capacity identification (RCI) scheme is proposed to design proper parameters for the SSWM system. To achieve steady-state voltage control, the system efficiency characteristic is analyzed in detail and the efficiency optimization can be achieved without an auxiliary dc/dc converter. The influence of impedance matching, the power capacity of the system, and overmodulation of the motor drive are all investigated. Then, the dynamic model of the system is established to analyze the stability of dc-link voltage. In the proposed feedforward voltage boost control, the dc-link voltage is boosted according to the motor operation state to increase the instantaneous power capacity. The dc-link voltage stability is improved and the system resilience is enhanced against power disturbance. Besides, at the end of the acceleration process, the dc-link voltage is smoothly adjusted to the optimal dc-link voltage. The effectiveness of the proposed RCI scheme and DCVR strategy is verified by experiments on a three-phase wireless permanent magnet synchronous motor platform.
Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), ...especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.
This paper proposes a wireless open-winding motor (WOWM) system, where noncontact operation can be achieved with the magnetic coupler. Thus, the flexibility and reliability of the WOWM system can be ...improved. Two isolated DC voltage ports for the open-winding motor can be obtained with only one DC voltage source, which facilitates the application of the system. The zero-sequence current in the motor winding can be suppressed and the DC link voltage utilization rate can be maximized owing to the isolated DC link structure. Besides, the operation characteristics of the WOWM system are analyzed in detail. The decoupled dual-receivers are designed, which ensures that the ratio of DC link voltages is load-independent. Moreover, the influences of misalignment on the WOWM system, including the overmodulation and increased phase current ripple are presented. The DC link voltage regulation (DVR) and active power allocation (APA) strategy are further proposed. The DC link voltage reference is identified based on the operating state of the motor for high performance operation. The allocation coefficient, k is adjusted according to the extent of misalignment, which improves the anti-misalignment capability. The feasibility of the WOWM system and the effectiveness of the DVR and APA strategy are verified by experiments.
The wireless heat transfer (WHT) system is proposed to ensure the reliability and flexibility of the electrical heat tracing for domestic and industrial applications. In this article, the inherent ...coupling relationship among coil dimension, resistance, distance, and inductance of a WHT system is investigated, which illustrates the intrinsic link between thermal energy and electromagnetic feature of the WHT system under multiple mediums. Besides, the magnitude and distribution of the thermal energy among different coils are analyzed according to equivalent circuits and magnetic coupling mechanisms. For further studying the power distribution characteristic, the power flow model of the multiple coil system is established. On this basis, the uniform thermal energy distribution scheme of the WHT system is proposed to ensure all coils have equal heating power. Moreover, the heating power in the partial compensation condition is also investigated. The result indicates the compensation states of the transmitter coil only affect the magnitude of the heating power. Thus, the transmitter coil compensation states which can be used to adjust the heating capacity of the WHT system. The simulation and experiments are carried out to validate the feasibility of the proposed uniform thermal energy distribution scheme.
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