Torsion Graph Neural Networks

Geometric deep learning (GDL) models have demonstrated a great potential for the analysis of non-Euclidian data. They are developed to incorporate the geometric and topological information of non-Euclidian data into the end-to-end deep learning architectures. Motivated by the recent success of discrete Ricci curvature in graph neural network (GNNs), we propose TorGNN, an analytic Torsion enhanced Graph Neural Network model. The essential idea is to characterize graph local structures with an analytic torsion based weight formula. Mathematically, analytic torsion is a topological invariant that can distinguish spaces which are homotopy equivalent but not homeomorphic. In our TorGNN, for each edge, a corresponding local simplicial complex is identified, then the analytic torsion (for this local simplicial complex) is calculated, and further used as a weight (for this edge) in message-passing process. Our TorGNN model is validated on link prediction tasks from sixteen different types of networks and node classification tasks from three types of networks. It has been found that our TorGNN can achieve superior performance on both tasks, and outperform various state-of-the-art models. This demonstrates that analytic torsion is a highly efficient topological invariant in the characterization of graph structures and can significantly boost the performance of GNNs

IMAP: Intrinsically Motivated Adversarial Policy

Reinforcement learning agents are susceptible to evasion attacks during deployment. In single-agent environments, these attacks can occur through imperceptible perturbations injected into the inputs of the victim policy network. In multi-agent environments, an attacker can manipulate an adversarial opponent to influence the victim policy's observations indirectly. While adversarial policies offer a promising technique to craft such attacks, current methods are either sample-inefficient due to poor exploration strategies or require extra surrogate model training under the black-box assumption. To address these challenges, in this paper, we propose Intrinsically Motivated Adversarial Policy (IMAP) for efficient black-box adversarial policy learning in both single- and multi-agent environments. We formulate four types of adversarial intrinsic regularizers -- maximizing the adversarial state coverage, policy coverage, risk, or divergence -- to discover potential vulnerabilities of the victim policy in a principled way. We also present a novel Bias-Reduction (BR) method to boost IMAP further. Our experiments validate the effectiveness of the four types of adversarial intrinsic regularizers and BR in enhancing black-box adversarial policy learning across a variety of environments. Our IMAP successfully evades two types of defense methods, adversarial training and robust regularizer, decreasing the performance of the state-of-the-art robust WocaR-PPO agents by 34%-54% across four single-agent tasks. IMAP also achieves a state-of-the-art attacking success rate of 83.91% in the multi-agent game YouShallNotPass

PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, however, its function in inhibiting telomerase activity of tumor cells is not well documented. Here we show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma.</p> <p>Methods</p> <p>Expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into NPC. Their effects on mRNA of telomerase catalytic subunit (hTERT), telomerase activity, cell proliferation, cell migration, wound healing, cell cycles and apoptosis were examined using semi-quantitative RT-PCR, stretch PCR, MTT assay, Transwell, scratch assay and flow cytometry, respectively.</p> <p>Results</p> <p>Transfection of pEGFP-C3-PinX1 and PinX1-FAM-siRNA increased and reduced PinX1 mRNA by 1.6-fold and 70%, respectively. Over-expression of PinX1 decreased hTERT mRNA by 21%, reduced telomerase activity, inhibited cell growth, migration and wound healing ability, arrested cells in G0/G1 phase, and increased apoptotic index. In contrast, down-regulation of PinX1 did not alter the above characteristics.</p> <p>Conclusions</p> <p>PinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor-targeted gene therapy.</p

Comparison of Chemical Compositions of the Pepper EOs From Different Cultivars and Their AChE Inhibitory Activity

© The Author(s) 2020. Pepper is one of the most popular spices over the world and is called the King of Spices. Its essential oils (EOs) could alleviate neuronal ailments due to the inhibitory effect against acetylcholinesterase (AChE). In this study, the chemical compositions of 26 EOs prepared from white and black pepper collecting from 6 different cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 133 compounds were identified in the white and black pepper EOs. Monoterpenes and sesquiterpenes were found to be riched in these EOs, of which α-pinene, β-pinene, sabinene, 3-carene, limonene, and (E)-β-caryophyllene were the major constituents. Most of pepper EOs showed potential AChE inhibitory activity with half-maximal inhibitory concentration (IC50) values in the range of 0.5-182.5 µg/mL. Comparison of chemical constitutes of pepper EOs from different cultivars suggested that α-pinene, β-pinene, and 3-carene with an IC50 value of 3.2, 53.3, and 2.9 µg/mL, respectively, might be used as Quality-marker (Q-marker) of pepper oil in inhibiting AChE

Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer

<p>Abstract</p> <p>Background/Aim</p> <p>To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).</p> <p>Materials/Methods</p> <p>Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.</p> <p>Results</p> <p>Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.</p> <p>Conclusion</p> <p>The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.</p

Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development

Jarid2 is part of the Polycomb Repressor complex 2 (PRC2) responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs), however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2−/− ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2−/− with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development.This study was supported by the Medical Research Council, the ERC (H.B. and J.S.-R.) (#294627), the HFSP (I.C.), and the Spanish Ministry of Economy and Competitiveness (D.L. and H.G.A.) (RYC-2012-10019; SAF2013-40891-R)