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This work aims to tackle a major challenge in offline Inverse Reinforcement Learning (IRL), namely the reward extrapolation error, where the learned reward function may fail to explain the task correctly and misguide the agent in unseen environments due to the intrinsic covariate shift. Leveraging both expert data and lower-quality diverse data, we devise a principled algorithm (namely CLARE) that solves offline IRL efficiently via integrating "conservatism" into a learned reward function and utilizing an estimated dynamics model. Our theoretical analysis provides an upper bound on the return gap between the learned policy and the expert policy, based on which we characterize the impact of covariate shift by examining subtle two-tier tradeoffs between the exploitation (on both expert and diverse data) and exploration (on the estimated dynamics model). We show that CLARE can provably alleviate the reward extrapolation error by striking the right exploitation-exploration balance therein. Extensive experiments corroborate the significant performance gains of CLARE over existing state-of-the-art algorithms on MuJoCo continuous control tasks (especially with a small offline dataset), and the learned reward is highly instructive for further learning.

Supplementary tables S1–S3.

Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3/LINC00662/miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 193 pathologically diagnosed TNBC patients from 2016 to 2017 in our hospital. Quantitative real-time PCR was used to evaluate the expression of LINC00662 and miR-186-5p both in vivo and in vitro. CCK8 tests were used to assess cell viability. ELISA was used for protein expression evaluation. Dual luciferase reporter gene assay and RNA pull-down were used to evaluate the interaction between LINC00662 and miR-186-5p. m6A levels were enhanced in breast cancer tissues and cells. LINC00662, miR-186-5p and METTL3 were differentially expressed in vivo, and METTL3 expression was associated with LINC00662 and miR-186-5p expression. LINC00662 and miR-186-5p were differentially expressed in vitro; LINC00662 promoted cell viability and decreased the apoptosis rate, whereas miR-186-5p inhibited cell viability and increased the apoptosis rate. Furthermore, we found that METTL3 regulated m6A levels in docetaxel-resistant breast cancer cells by regulating the expression of LINC00662. Moreover, LINC00662 and miR-186-5p regulated the cell viability rate of docetaxel-resistant breast cancer cells. Further experiments showed that LINC00662 directly interacted with miR-186-5p to exert biological functions; besides miR-186-5p could regulate the expression of METTL3. METTL3 promotes m6A levels and docetaxel resistance in breast cancer by regulating the expression of LINC00662 and miR-186-5p; more experiments are needed to clarify the role of m6A regulation in drug resistance.

Additional file 3: Fig. 1. Cell communication analysis between 14 cluster cells. Circle plot shows the number of interactions and interaction weights/strength of 14 cluster cells between case and control.

Additional file 1: Table 1: Primers for genes validated using qRT-PCR and pyrosequencing sequencing primers. Table 3. The methylation levels of CpG sites in the promoter regions of FLT1 and IGF2BP1 were detected by pyrosequencing. Table 4: Descriptive indices of air pollutants and climate factors in the city Tianjin from January 1, 2017 to December 31, 2018 (reported as per day). Table 5: PLS-PM analysis for the relationships between latent variables.

Additional file 4: Fig. 2. Molecular details and subclusters of dNKs were revealed by scRNA-seq. (A) A UMAP projection of the dNKs from one RSA patient and one matched healthy control. Different colors indicate cell clusters. (B) Dot plot shows the expression of marker genes for each subcluster of dNK. (C) Dot plot shows the expression of cell cycle-related genes. (D) Developmental trajectories of dNK subsets, cells colored by conditions of trajectories state, groups, subclusters, and pseudotime.

Additional file 6: Fig. 4. Analysis of IGF2BP1 expression and its promoter region. (A) ROC analysis of methylation of IGF2BP1 in patient with RSA and controls. (B) scRNA-seq analysis of the expression of IGF2BP1 in 14 cell subsets. (C) Distribution of CpG island in the IGF2BP1 promoter region. (D) Prediction of transcription factors binding to each CpG island.

Additional file 6: Fig. 4. Analysis of IGF2BP1 expression and its promoter region. (A) ROC analysis of methylation of IGF2BP1 in patient with RSA and controls. (B) scRNA-seq analysis of the expression of IGF2BP1 in 14 cell subsets. (C) Distribution of CpG island in the IGF2BP1 promoter region. (D) Prediction of transcription factors binding to each CpG island.

Additional file 7: Fig. 5. The relationship between air pollution-related genes and RSA. (A) and (B) Monthly air pollutant concentration curve from 2014 to 2018. (C) Correlation heatmap plot shows the association between six air pollutants.

Additional file 7: Fig. 5. The relationship between air pollution-related genes and RSA. (A) and (B) Monthly air pollutant concentration curve from 2014 to 2018. (C) Correlation heatmap plot shows the association between six air pollutants.

Additional file 5: Fig. 3. Molecular details and subclusters of dM were revealed by scRNA-seq. (A) A UMAP projection of the dM from three RSA patients and three matched healthy controls. Different colors indicate cell clusters. (B) Dot plot shows the expression of marker genes for each subcluster of dM. (C) Dot plot shows the expression of cell cycle-related genes. (D) Developmental trajectories of dM subsets, cells colored by conditions of trajectories state, groups, subclusters, and pseudotime.

Evaluation reliability of high-reliability and long-life electronic equipment under multiple stress conditions is urgently needed. Based on the Weibull pseudo-life test evaluation method, this paper analyzes the accelerated degradation test data of a certain type of communication equipment power module. Firstly, this paper introduces the accelerated test plan of a certain type of communication equipment power module, and gives the method of pseudo life test evaluation. Secondly, based on the Generalized Irene-Polynomial model, combined with the actual power unit test program, the parameter Bootstrap method is used to obtain the interval estimation of the model parameters. Finally, the reliability and confidence interval of the power module under normal stress are given.

Xanthine oxidase (XO) is a critical target for the therapy of hyperuricemia and gout. In this study, a number of 3-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-1,2,4-oxadiazol-5(4H)-ones (3a–3w) were newly designed by a bioisosteric replacement and hybrid strategy with the hope of obtaining novel and effective nonpurine XO inhibitors. Subsequently, these compounds were synthesized through a three-step procedure, with good yields. In addition, the in vitro bovine XO inhibitions were measured by spectrophotometric determination of uric acid formation at 295 nm using allopurinol as a positive control. As a result, compound 3j was found to be the most potent XO inhibitor, with an IC50 value of 0.121 µM, which was approximately 63-fold more potent than allopurinol, and the analysis of the structure-activity relationships indicated that the hydrophobic group at 4′-position was essential for inhibitory potency. Additionally, the molecular modeling results showed that the 1,2,4-oxadiazol-5(4H)-one moiety binds to XO active site via various hydrogen bonds with Arg880 and Thr1010. Moreover, the compound 3j was demonstrated to be a mixed-type nonpurine XO inhibitor. Furthermore, the hypouricemic studies on a rat model, induced by potassium oxonate, demonstrated that serum uric acid levels could be effectually reduced by compound 3j at an oral dose of 15 mg/kg. Therefore, compound 3j could be a promising lead compound for the treatment of hyperuricemia and gout.

Most switching-mode power amplifiers are made up of multiple modules running in parallel redundant operation mode. The complex structure and operation mode make fault diagnosis and prediction difficult to design and develop. Effective fault prediction is required to improve operational reliability of amplifier systems, by achieving pre-maintenance of the system to avoid major accidents and reduce maintenance costs. This paper uses the special structure of dynamic decision networks and their ability to process time series data to perform probabilistic reasoning and to build a dynamic Bayesian network model. A numerical simulation model for the state variables that characterize the system fault is also established. This is to generate a number of simulation data to describe the change in fault state variables under different working conditions during different running modes. Using these data, the feasibility of the fault prediction model of the switch mode power amplifier is illustrated and verified.

Climate variability during the Late Pleistocene is studied from the proxies in core CK-2 drilled from the Luobei Depression (91°03′E, 40°47′N), Lop Nur in the eastern Tarim Basin, Xinjiang, China. Geophysical and geochemical properties, including magnetic susceptibility, granularity, chroma, carbonate content, loss on ignition and trace elements, have been determined to reconstruct the environmental evolution of the area during 32–9 ka BP. The chronology is established by uranium–thorium disequilibrium dating techniques. Our data suggest four paleoclimate stages, indicating glacial variations between cold–humid and warm–arid environments. A period of extreme humidity occurred during 31,900–19,200 yr BP is attributed the last glacial maximum (LGM). The period was followed by a warm–arid episode during 19,200–13,500 yr BP. Then a cold–humid interval during 13,500–12,700 yr BP may correspond to another cooling phases at high latitudes of the Northern Hemisphere. The last stage from 12,700 to 9000 yr BP has a trend that the climate turned warm and arid. The Lop Nur region is characterized by particularly humid stadials and arid interstadials. The climate variability in Lop Nur was constrained by global climate change because it is correlated with Dansgaard–Oeschger and Heinrich events, which were observed at the northern high latitudes. The synchroneity of the palaeoclimatic events suggested that cold air activity at the northern high latitudes was the most important factor that influenced the climate evolution in the Lop Nur region. A probable mechanism that involves the migration of westerly winds is proposed to interpret this synchroneity.

The symposium on nongovernmental basic education sponsored by the Guangzhou Zhonghua Yinghao School, the Guangzhou Modern Education Science Center, and the magazine Zhongxiaoxue jiaoyu guanli (Management of elementary and secondary school education) was held in Conghua, Guangzhou, from May 29 to May 31. Representatives of sixteen nongovernmental schools in Beijing, Tianjin, Shanghai, Shenyang, Sichuan, Anhui, Hainan, and Guangdong participated. Leading personnel and experts from the Statutes and Law Bureau of the State Council and relevant departments of the State Education Commission and from the Guangzhou Education Commission were also invited to attend. In his opening address, Comrade Wu Ziyan, director of Guangzhou's Modern Education Science Center, proposed the following topics for discussion: the position and role of nongovernmental elementary and secondary schools in the development of socialist education; how nongovernmental elementary and secondary schools should handle the relationship between t...

Technological trends discovery has been paid attention seriously in recent years in technological innovation management because of great demands on R&D decision making from the governments and various organizations. In this paper, the framework integrating with technology coupling, IPC co-occurrence, complex networks and visualization would be developed. The paper first introduces the technology coupling theory which is developed by Fleming and can be used to measure the utility of patent. Then the application of IPC co-occurrence and complex network base on technology coupling theory is designed. At last, we make the empirical study on hybrid electric vehicle field. The empirical study identifies that our framework helps to discover and mine the technological trends at the company level.

Circular groove guide is a new type of transmission line with some attractive advantages. The experiments described in this paper have demonstrated the possibility of power combining of W band circular groove guide.

Summary form only given, as follows. Two kinds of discontinuities are analyzed in this paper. The discontinuity of a DC isolation slot is analyzed with the FDTD method, and the discontinuity of a full-height fin-line short end with the SDA method. S-parameters of the DC isolation slot and the effective transmission length are obtained. Based on the numerical results, low insertion loss reflection-type phase shifters at 38 GHz and 94 GHz are successfully achieved.

This paper describes an ultralow power wireless intraocular pressure (IOP) monitoring system that is dedicated to sensing and transferring intraocular pressure of glaucoma patients. Our system is comprised of a capacitive pressure sensor, an application-specific integrated circuit, which is designed on the SMIC 180 nm process, and a dipole antenna. The system is wirelessly powered and demonstrates a power consumption of 7.56 μW at 1.24 V during continuous monitoring, a significant reduction in active power dissipation compared to existing work. The input RF sensitivity is −13 dBm. A significant reduction in input RF sensitivity results from the reduction of mismatch time of the ASK modulation caused by FM0 encoding. The system exhibits an average error of ± 1.5 mmHg in measured pressure. Finally, a complete IOP system is demonstrated in the real biological environment, showing a successful reading of the pressure of an eye.

A wide bandwidth continuous time sigma delta ADC is implemented in 130 nm CMOS. A detailed non-idealities analysis (excess loop delay, clock jitter, finite gain and GBW, comparator offset and DAC mismatch) is performed developed in Matlab/Simulink. This design is targeted for wide bandwidth applications such as video or wireless base-stations. Athird-order continuous time sigma delta modulator comprises a third-order RC operational-amplifier-based loop filter and 3-bit internal quantizer operated at 512 MHz clock frequency. The sigma delta ADC achieves 60 dB SNR and 59.3 dB SNDR over a 16-MHz signal band at an OSR of 16. The power consumption of the CT sigma delta modulator is 22 mW from the 1.2-V supply.

Background and Objectives: Tryptophan hydroxylase 2 (TPH2) catalyzes the rate-limiting step in serotonin biosynthesis in the nervous system. Several variants of human TPH2 have been reported to be associated with a spectrum of neuropsychiatric disorders such as unipolar major depression, bipolar disorder and suicidality etc. Recent studies suggested that two variants (T212 and A375) in the exon 7 and exon 9 were associated with major depressive disorder (MDD). Methods: To replicate these findings, two polymorphisms located in exons 7 and 9 of TPH2 (rs7305115 and rs4290270, respectively) were analysed by DNA sequence in the case-control sample study in 191 MDD and 191 healthy volunteers. Statistical analyses were carried out using the program SPSS. The comparison of allele and genotype frequencies of each polymorphism between case and control groups was carried out on the online software SHEsis. All subjects were unrelated southern Han Chinese. Results: No difference was observed on the allelic or genotypic distribution of TPH2 gene polymorphisms between the groups. However, the two-marker haplotype covering components T212 (rs7305115) A and A375 (rs4290270) T were observed to have a significantly protective effect MDD in female (corrected p = 0.0032; OR = 0.241[95% CI = 0.099-0.587]). Conclusions: The results suggest that TPH2 might be associated with a lower risk of female MDD. However, confirmatory studies in independent samples are needed.