Hybrid PolyLingual Object Model: An Efficient and Seamless Integration of Java and Native Components on the Dalvik Virtual Machine

Copyright © 2014 Yukun Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. JNI in the Android platform is often observed with low efficiency and high coding complexity. Although many researchers have investigated the JNI mechanism, few of them solve the efficiency and the complexity problems of JNI in the Android platform simultaneously. In this paper, a hybrid polylingual object (HPO) model is proposed to allow a CAR object being accessed as a Java object and as vice in the Dalvik virtual machine. It is an acceptable substitute for JNI to reuse the CAR-compliant components in Android applications in a seamless and efficient way. The metadata injection mechanism is designed to support the automatic mapping and reflection between CAR objects and Java objects. A prototype virtual machine, called HPO-Dalvik, is implemented by extending the Dalvik virtual machine to support the HPO model. Lifespan management, garbage collection, and data type transformation of HPO objects are also handled in the HPO-Dalvik virtual machine automatically. The experimental result shows that the HPO model outweighs the standard JNI in lower overhead on native side, better executing performance with no JNI bridging code being demanded. 1

Cytolethal Distending Toxin-Induced Release of Interleukin-1β by Human Macrophages is Dependent Upon Activation of Glycogen Synthase Kinase 3β, Spleen Tyrosine Kinase (Syk) and the Noncanonical Inflammasome

Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. We have previously demonstrated that the Aggregatibacter actinomycetemcomitans Cdt induces a pro-inflammatory response from human macrophages which involves activation of the NLRP3 inflammasome. We now demonstrate that in addition to activating caspase-1 (canonical inflammasome), Cdt treatment leads to caspase-4 activation and involvement of the noncanonical inflammasome. Cdt-treated cells exhibit pyroptosis characterised by cleavage of gasdermin-D (GSDMD), release of HMGB1 at 24 hr and LDH at 48 hr. Inhibition of either the canonical (caspase-1) or noncanonical (caspase-4) inflammasome blocks both Cdt-induced release of IL-1β and induction of pyroptosis. Analysis of upstream events indicates that Cdt induces Syk phosphorylation (activation); furthermore, blockade of Syk expression and inhibition of pSyk activity inhibit both Cdt-induced cytokine release and pyroptosis. Finally, we demonstrate that increases in pSyk are dependent upon Cdt-induced activation of GSK3β. These studies advance our understanding of Cdt function and provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as A. actinomycetemcomitans. © 2020 John Wiley & Sons Lt

NLRX1 modulates differentially NLRP3 inflammasome activation and NF-κB signaling during Fusobacterium nucleatum infection

NOD-like receptors (NLRs) play a large role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, enhances mitochondrial ROS (mROS) generation. mROS can activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-induced NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). We found that depletion of NLRX1 by shRNA attenuated ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, ASC. Furthermore, depletion of NLRX1 inhibited Fusobacterium nucleatum infection-activated caspase-1, suggesting that it also inhibits the NLRP3 inflammasome. Conversely, NLRX1 also acted as a negative regulator of NF-κB signaling and IL-8 expression. Thus, NLRX1 stimulates detection of the pathogen F. nucleatum via the inflammasome, while dampening cytokine production. We expect that commensals should not activate the inflammasome, and NLRX1 should decrease their ability to stimulate expression of pro-inflammatory cytokines such as IL-8. Therefore, NLRX1 may act as a potential switch with regards to anti-microbial responses in healthy or diseased states in the oral cavity

MiniZero: Comparative Analysis of AlphaZero and MuZero on Go, Othello, and Atari Games

This paper presents MiniZero, a zero-knowledge learning framework that supports four state-of-the-art algorithms, including AlphaZero, MuZero, Gumbel AlphaZero, and Gumbel MuZero. While these algorithms have demonstrated super-human performance in many games, it remains unclear which among them is most suitable or efficient for specific tasks. Through MiniZero, we systematically evaluate the performance of each algorithm in two board games, 9x9 Go and 8x8 Othello, as well as 57 Atari games. For two board games, using more simulations generally results in higher performance. However, the choice of AlphaZero and MuZero may differ based on game properties. For Atari games, both MuZero and Gumbel MuZero are worth considering. Since each game has unique characteristics, different algorithms and simulations yield varying results. In addition, we introduce an approach, called progressive simulation, which progressively increases the simulation budget during training to allocate computation more efficiently. Our empirical results demonstrate that progressive simulation achieves significantly superior performance in two board games. By making our framework and trained models publicly available, this paper contributes a benchmark for future research on zero-knowledge learning algorithms, assisting researchers in algorithm selection and comparison against these zero-knowledge learning baselines. Our code and data are available at https://rlg.iis.sinica.edu.tw/papers/minizero.Comment: Submitted to IEEE Transactions on Games, under revie

Kinetics, Energetics, and Size Dependence of the Transformation from Pt to Ordered PtSn Intermetallic Nanoparticles

The outstanding catalytic activity and chemical selectivity of intermetallic compounds make them excellent candidates for heterogeneous catalysis. However, the kinetics of their formation at the nanoscale is poorly understood or characterized, and precise control of their size, shape as well as composition during synthesis remains challenging. Here, using well-defined Pt nanoparticles (5 nm and 14 nm) encapsulated in mesoporous silica, we study the transformation kinetics from monometallic Pt to intermetallic PtSn at different temperatures by a series of time-evolution X-ray diffraction studies. Observations indicate an initial transformation stage mediated by Pt surface-controlled intermixing kinetics, followed by a second stage with distinct transformation kinetics corresponding to a Ginstling-Brounstein (G-B) type bulk diffusion mode. Moreover, the activation barrier for both surface intermixing and diffusion stages are obtained through the development of appropriate kinetic models for analysis of experimental data. Our density-functional-theory (DFT) calculations provide further insights into the atomistic-level processes and associated energetics underlying surface-controlled intermixing

Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1.

Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs

Amniotic fluid-derived mesenchymal stem cells as a novel therapeutic approach in the treatment of fulminant hepatic failure in rats

As a potential alternative treatment for terminal liver diseases, amniotic fluid derived mesenchymal stem cells (AFMSCs) have many advantages over other stem cells: avoiding much ethical controversy and decrease in both quantity and differentiation potential with age. However, the therapeutic role of AFMSC for fulminant hepatic failure (FHF) has not yet been clearly elucidated. Therefore, we investigated the reparation effects of transplanted AFMSCs in rats with FHF. AFMSCs were transplanted into injured liver via the portal vein in the rat FHF model. Therapeutic effect was evaluated after cell transfusion by histologic pathology, hepatic enzyme levels and animal survival. Cryostat sections were prepared and directly assessed for green fluorescent protein (GFP) expression and localization, and in vivo differentiation of AFMSC was confirmed by double-immunostaining analyses. Our results show that AFMSCs prevented liver failure and reduced mortality in rats with FHF. These animals also exhibited improved liver function and animals survival after injection with AFMSCs using GFP, we demonstrated that the engrafted cells and their progeny incorporated into injured livers and produced albumin. We found that AFMSCs transplantation modestly promoted the repair of FHF in rats. AFMSCs implanted in the injured liver may be a novel therapeutic approach in the treatment of FHF.Key words: Amniotic fluid-derived mesenchymal stem cells, fulminant hepatic failure, cell transplantation, treatment, hepatogenic differentiation