Neural topic modeling with bidirectional adversarial training

Recent years have witnessed a surge of interests of using neural topic models for automatic topic extraction from text, since they avoid the complicated mathematical derivations for model inference as in traditional topic models such as Latent Dirichlet Allocation (LDA). However, these models either typically assume improper prior (e.g. Gaussian or Logistic Normal) over latent topic space or could not infer topic distribution for a given document. To address these limitations, we propose a neural topic modeling approach, called Bidirectional Adversarial Topic (BAT) model, which represents the first attempt of applying bidirectional adversarial training for neural topic modeling. The proposed BAT builds a two-way projection between the document-topic distribution and the document-word distribution. It uses a generator to capture the semantic patterns from texts and an encoder for topic inference. Furthermore, to incorporate word relatedness information, the Bidirectional Adversarial Topic model with Gaussian (Gaussian-BAT) is extended from BAT. To verify the effectiveness of BAT and Gaussian-BAT, three benchmark corpora are used in our experiments. The experimental results show that BAT and Gaussian-BAT obtain more coherent topics, outperforming several competitive baselines. Moreover, when performing text clustering based on the extracted topics, our models outperform all the baselines, with more significant improvements achieved by Gaussian-BAT where an increase of near 6% is observed in accuracy

Intrinsic nonlinear Hall effect and gate-switchable Berry curvature sliding in twisted bilayer graphene

Though the observation of quantum anomalous Hall effect and nonlocal transport response reveals nontrivial band topology governed by the Berry curvature in twisted bilayer graphene, some recent works reported nonlinear Hall signals in graphene superlattices which are caused by the extrinsic disorder scattering rather than the intrinsic Berry curvature dipole moment. In this work, we report a Berry curvature dipole induced intrinsic nonlinear Hall effect in high-quality twisted bilayer graphene devices. We also find that the application of the displacement field substantially changes the direction and amplitude of the nonlinear Hall voltages, as a result of a field-induced sliding of the Berry curvature hotspots. Our work not only proves that the Berry curvature dipole could play a dominant role in generating the intrinsic nonlinear Hall signal in graphene superlattices with low disorder densities, but also demonstrates twisted bilayer graphene to be a sensitive and fine-tunable platform for second harmonic generation and rectification

Thiabendazole Inhibits Glioblastoma Cell Proliferation and Invasion Targeting Mini-chromosome Maintenance Protein 2

Thiabendazole (TBZ), approved by the US Food and Drug Administration (FDA) for human oral use, elicits a potential anticancer activity on cancer cells in vitro and in animal models. Here, we evaluated the efficacy of TBZ in the treatment of human glioblastoma multiforme (GBM). TBZ reduced the viability of GBM cells (P3, U251, LN229, A172, and U118MG) relative to controls in a dose- and time-dependent manner. However, normal human astrocytes (NHA) exhibited a greater IC50 than tumor cell lines and were thus more resistant to its cytotoxic effects. 5-Ethynyl-2′-deoxyuridine (EdU)-positive cells and the number of colonies formed were decreased in TBZ-treated cells (at 150 μM, P < 0.05 and at 150 μM, P < 0.001, respectively). This decrease in proliferation was associated with a G2/M arrest as assessed with flow cytometry, and the downregulation of G2/M check point proteins. In addition, TBZ suppressed GBM cell invasion. Analysis of RNA sequencing data comparing TBZ-treated cells with controls yielded a group of differentially expressed genes, the functions of which were associated with the cell cycle and DNA replication. The most significantly downregulated gene in TBZ-treated cells was mini-chromosome maintenance protein 2 (MCM2). SiRNA knockdown of MCM2 inhibited proliferation, causing a G2/M arrest in GBM cell lines and suppressed invasion. Taken together, our results demonstrated that TBZ inhibited proliferation and invasion in GBM cells through targeting of MCM2.publishedVersio

DetZero: Rethinking Offboard 3D Object Detection with Long-term Sequential Point Clouds

Existing offboard 3D detectors always follow a modular pipeline design to take advantage of unlimited sequential point clouds. We have found that the full potential of offboard 3D detectors is not explored mainly due to two reasons: (1) the onboard multi-object tracker cannot generate sufficient complete object trajectories, and (2) the motion state of objects poses an inevitable challenge for the object-centric refining stage in leveraging the long-term temporal context representation. To tackle these problems, we propose a novel paradigm of offboard 3D object detection, named DetZero. Concretely, an offline tracker coupled with a multi-frame detector is proposed to focus on the completeness of generated object tracks. An attention-mechanism refining module is proposed to strengthen contextual information interaction across long-term sequential point clouds for object refining with decomposed regression methods. Extensive experiments on Waymo Open Dataset show our DetZero outperforms all state-of-the-art onboard and offboard 3D detection methods. Notably, DetZero ranks 1st place on Waymo 3D object detection leaderboard with 85.15 mAPH (L2) detection performance. Further experiments validate the application of taking the place of human labels with such high-quality results. Our empirical study leads to rethinking conventions and interesting findings that can guide future research on offboard 3D object detection.Comment: 17 pages, 8 figure

TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein

Background The tripartite motif (TRIM) family of proteins plays a key role in the developmental growth and therapeutic resistance of many tumors. However, the regulatory mechanisms and biological functions of TRIM proteins in human glioblastoma (GBM) are not yet fully understood. In this study, we focused on TRIM56, which emerged as the most differentially expressed TRIM family member with increased expression in GBM. Methods Western blot, real-time quantitative PCR (qRT-PCR), immunofluorescence (IF) and immunohistochemistry (IHC) were used to study the expression levels of TRIM56 and cIAP1 in GBM cell lines. Co-immunoprecipitation (co-IP) was used to explore the specific binding between target proteins and TRIM56. A xenograft animal model was used to verify the tumor promoting effect of TRIM56 on glioma in vivo. Results We observed elevated expression of TRIM56 in malignant gliomas and revealed that TRIM56 promoted glioma progression in vitro and in a GBM xenograft model in nude mice. Analysis of the Human Ubiquitin Array and co-IPs showed that cIAP1 is a protein downstream of TRIM56. TRIM56 deubiquitinated cIAP1, mainly through the zinc finger domain (amino acids 21–205) of TRIM56, thereby reducing the degradation of cIAP1 and thus increasing its expression. TRIM56 also showed prognostic significance in overall survival of glioma patients. Conclusions TRIM56-regulated post-translational modifications may contribute to glioma development through stabilization of cIAP1. Furthermore, TRIM56 may serve as a novel prognostic indicator and therapeutic molecular target for GBM.publishedVersio

Replication timing maintains the global epigenetic state in human cells

ACKNOWLEDGMENTS We thank R. Didier and B. Alexander of the FSU Flow Cytometry and Confocal Microscopy Facilities for their help with flow cytometry and fluorescence-activated cell sorting for this project. Thanks to A. Brown of the FSU Biological Science Core Labs and to Y. Yang and C. Vied of the FSU Translational Labs. Thanks to S. R. Westermann of SCIGRAPHIX for generating the model figure. Thanks to B. van Steensel, J. Phillips-Cremins, and P. Fraser for critical reading of the manuscript. Funding: This work was supported by NIH grant GM083337 to D.M.G., GM035463 to V.G.C., and GM085354 to D.M.G., S.D., and V.G.C. D.L. is supported by the Hong Kong Research Grant Council (ECS 26104216). T.B. is supported by the William C. and Joyce C. O’Neil Charitable Trust, Memorial Sloan Kettering Single Cell Sequencing InitiativePeer reviewedPostprin