9,364 research outputs found
Tikuna: An Ethereum Blockchain Network Security Monitoring System
Blockchain security is becoming increasingly relevant in today's cyberspace
as it extends its influence in many industries. This paper focuses on
protecting the lowest level layer in the blockchain, particularly the P2P
network that allows the nodes to communicate and share information. The P2P
network layer may be vulnerable to several families of attacks, such as
Distributed Denial of Service (DDoS), eclipse attacks, or Sybil attacks. This
layer is prone to threats inherited from traditional P2P networks, and it must
be analyzed and understood by collecting data and extracting insights from the
network behavior to reduce those risks. We introduce Tikuna, an open-source
tool for monitoring and detecting potential attacks on the Ethereum blockchain
P2P network, at an early stage. Tikuna employs an unsupervised Long Short-Term
Memory (LSTM) method based on Recurrent Neural Network (RNN) to detect attacks
and alert users. Empirical results indicate that the proposed approach
significantly improves detection performance, with the ability to detect and
classify attacks, including eclipse attacks, Covert Flash attacks, and others
that target the Ethereum blockchain P2P network layer, with high accuracy. Our
research findings demonstrate that Tikuna is a valuable security tool for
assisting operators to efficiently monitor and safeguard the status of Ethereum
validators and the wider P2P networkComment: 15 pages, 2 figures, submitted to ISPEC 2023 Conferenc
Inflammation, DNA-centered radicals, and oxidative genotoxicity: The role of HOCl produced by myeloperoxidase in carcinogenesis
Myeloid cells (macrophages and neutrophils) infiltrate and synthesize myeloperoxidase (MPO) in sites of inflammation, producing gentotoxicity. In RAW 264.7 macrophages, bacterial lipopolysaccharide (LPS) induces superoxide radical anion, nuclear deformation (nuclear protuberances), MPO synthesis, biomolecule oxidation and cell death. “Freezing” LPS-triggered macrophage activation with the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) prevented cell activation and death. Oxidation of proteins and genomic DNA was also blocked, with formation of protein- and DNA-DMPO nitrone adducts, as analyzed by immuno-spin trapping with a polyclonal anti-DMPO serum. Interestingly, confocal microscopy analysis of these cells showed that MPO, genomic DNA, and DNA-DMPO nitrone adducts co-localized in the nuclear protuberances. These observations, and the fact that DNA is negatively charged and MPO is a cationic protein, suggest a role for uptaken or newly synthesized MPO in oxidative genotoxicity induced by myeloid cells in sites of inflammation. 
In order to understand MPO-induced formation of DNA-centered radicals, we studied DNA-DMPO nitrone adducts in calf thymus DNA treated with micromolar concentrations of hypochlorous acid (HOCl) added as a bolus or generated in situ by the MPO/H2O2/Cl- system in the presence of DMPO. We also investigated DNA-DMPO nitrone adducts inside living cells containing MPO. The cell models we used were: i) human leukemia (HL)-60 cells, which overexpress MPO, ii) RAW 264.7 macrophages activated with LPS (1 ng/ml for 24 h), to induce MPO, and iii) A549 human airway epithelial cells pre-loaded with human MPO. When these cells were activated with the phorbol ester PMA, the number of 6-thioguanine-resistant cells with the hypoxanthine-guanine phosphoribosyl transferase (HRPT) mutation increased. This mutation was prevented by each of the following: the NADPH oxidase inhibitor apocynin; the MPO inhibitors salicylhydroxamic acid and 4-aminobenzoic acid hydrazide; the cell-permeable HOCl scavenger resveratrol; and DMPO, which traps DNA-centered radicals and prevents further oxidation. 
Genomic DNA-centered radicals and further mutagenesis induced by activated myeloid cells in sites of inflammation can be prevented by blocking MPO activity, preventing formation of and/or scavenging HOCl, or trapping DNA-centered radicals. Our findings provide new therapeutic avenues for preventing carcinogenesis induced by infiltration and activation of myeloid cells in sites of inflammation, for example, in the lung exposed to particulate matter. SUPPORTED BY NIEHS 5R00ES015415-03

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