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

Optimizing Energy Transduction of Fluctuating Signals with Nanofluidic Diodes and Load Capacitors

This is the peer reviewed version of the following article: Ramirez Hoyos, P.; Cervera Montesinos, J.; Gómez Lozano, V.; Ali, M.; Nasir, S.; Ensinger, W.; Mafé, S. (2018). Optimizing Energy Transduction of Fluctuating Signals with Nanofluidic Diodes and Load Capacitors. Small. 14(18). doi:10.1002/smll.201702252, which has been published in final form at http://doi.org/10.1002/smll.201702252. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] The design and experimental implementation of hybrid circuits is considered allowing charge transfer and energy conversion between nanofluidic diodes in aqueous ionic solutions and conventional electronic elements such as capacitors. The fundamental concepts involved are reviewed for the case of fluctuating zero-average external potentials acting on single pore and multipore membranes. This problem is relevant to electrochemical energy conversion and storage, the stimulus-response characteristics of nanosensors and actuators, and the estimation of the accumulative effects caused by external signals on biological ion channels. Half-wave and full-wave voltage doublers and quadruplers can scale up the transduction between ionic and electronic signals. The network designs discussed here should be useful to convert the weak signals characteristic of the micro and nanoscale into robust electronic responses by interconnecting iontronics and electronic elements.P.R., J.C., V.G., and S.M. acknowledge the financial support from the Ministry of Economy and Competitiveness of Spain, (Materials Program, project No. MAT2015-65011-P), and FEDER. M.A., S.N., and W.E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO.Ramirez Hoyos, P.; Cervera Montesinos, J.; Gómez Lozano, V.; Ali, M.; Nasir, S.; Ensinger, W.; Mafé, S. (2018). Optimizing Energy Transduction of Fluctuating Signals with Nanofluidic Diodes and Load Capacitors. Small. 14(18). https://doi.org/10.1002/smll.201702252S1418Misra, N., Martinez, J. A., Huang, S.-C. J., Wang, Y., Stroeve, P., Grigoropoulos, C. P., & Noy, A. (2009). Bioelectronic silicon nanowire devices using functional membrane proteins. Proceedings of the National Academy of Sciences, 106(33), 13780-13784. doi:10.1073/pnas.0904850106Lemay, S. G. (2009). Nanopore-Based Biosensors: The Interface between Ionics and Electronics. ACS Nano, 3(4), 775-779. doi:10.1021/nn900336jTybrandt, K., Larsson, K. C., Richter-Dahlfors, A., & Berggren, M. (2010). Ion bipolar junction transistors. 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Net currents obtained from zero-average potentials in single amphoteric nanopores. Electrochemistry Communications, 31, 137-140. doi:10.1016/j.elecom.2013.03.026Gomez, V., Ramirez, P., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Converting external potential fluctuations into nonzero time-average electric currents using a single nanopore. Applied Physics Letters, 106(7), 073701. doi:10.1063/1.4909532Gomez, V., Ramirez, P., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Charging a Capacitor from an External Fluctuating Potential using a Single Conical Nanopore. Scientific Reports, 5(1). doi:10.1038/srep09501Queralt-Martín, M., García-Giménez, E., Aguilella, V. M., Ramirez, P., Mafe, S., & Alcaraz, A. (2013). Electrical pumping of potassium ions against an external concentration gradient in a biological ion channel. Applied Physics Letters, 103(4), 043707. doi:10.1063/1.4816748Verdia-Baguena, C., Gomez, V., Cervera, J., Ramirez, P., & Mafe, S. (2017). Energy transduction and signal averaging of fluctuating electric fields by a single protein ion channel. Physical Chemistry Chemical Physics, 19(1), 292-296. doi:10.1039/c6cp06035hGomez, V., Cervera, J., Nasir, S., Ali, M., Ensinger, W., Mafe, S., & Ramirez, P. (2016). Electrical network of nanofluidic diodes in electrolyte solutions: Connectivity and coupling to electronic elements. Electrochemistry Communications, 62, 29-33. doi:10.1016/j.elecom.2015.10.022Ramirez, P., Gomez, V., Verdia-Baguena, C., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2016). Designing voltage multipliers with nanofluidic diodes immersed in aqueous salt solutions. Physical Chemistry Chemical Physics, 18(5), 3995-3999. doi:10.1039/c5cp07203dRamirez, P., Gomez, V., Cervera, J., Nasir, S., Ali, M., Ensinger, W., … Mafe, S. (2016). Voltage-controlled current loops with nanofluidic diodes electrically coupled to solid state capacitors. RSC Advances, 6(60), 54742-54746. doi:10.1039/c6ra08277gRamirez, P., Garcia-Morales, V., Gomez, V., Ali, M., Nasir, S., Ensinger, W., & Mafe, S. (2017). Hybrid Circuits with Nanofluidic Diodes and Load Capacitors. Physical Review Applied, 7(6). doi:10.1103/physrevapplied.7.064035Ramirez, P., Gomez, V., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Energy conversion from external fluctuating signals based on asymmetric nanopores. Nano Energy, 16, 375-382. doi:10.1016/j.nanoen.2015.07.013Hou, Y., Vidu, R., & Stroeve, P. (2011). Solar Energy Storage Methods. Industrial & Engineering Chemistry Research, 50(15), 8954-8964. doi:10.1021/ie2003413Ali, M., Ahmed, I., Ramirez, P., Nasir, S., Mafe, S., Niemeyer, C. M., & Ensinger, W. (2017). A redox-sensitive nanofluidic diode based on nicotinamide-modified asymmetric nanopores. Sensors and Actuators B: Chemical, 240, 895-902. doi:10.1016/j.snb.2016.09.061Zhang, Y., & Schatz, G. C. (2017). Conical Nanopores for Efficient Ion Pumping and Desalination. The Journal of Physical Chemistry Letters, 8(13), 2842-2848. doi:10.1021/acs.jpclett.7b01137Apel, P. (2001). Track etching technique in membrane technology. Radiation Measurements, 34(1-6), 559-566. doi:10.1016/s1350-4487(01)00228-1Siwy, Z., Trofin, L., Kohli, P., Baker, L. A., Trautmann, C., & Martin, C. R. (2005). Protein Biosensors Based on Biofunctionalized Conical Gold Nanotubes. Journal of the American Chemical Society, 127(14), 5000-5001. doi:10.1021/ja043910fRamirez, P., Ali, M., Ensinger, W., & Mafe, S. (2012). Information processing with a single multifunctional nanofluidic diode. Applied Physics Letters, 101(13), 133108. doi:10.1063/1.4754845Cervera, J., Ramirez, P., Gomez, V., Nasir, S., Ali, M., Ensinger, W., … Mafe, S. (2016). Multipore membranes with nanofluidic diodes allowing multifunctional rectification and logical responses. Applied Physics Letters, 108(25), 253701. doi:10.1063/1.4954764Nasir, S., Ramirez, P., Ali, M., Ahmed, I., Fruk, L., Mafe, S., & Ensinger, W. (2013). Nernst-Planck model of photo-triggered, pH–tunable ionic transport through nanopores functionalized with «caged» lysine chains. The Journal of Chemical Physics, 138(3), 034709. doi:10.1063/1.4775811Pérez-Mitta, G., Albesa, A. G., Trautmann, C., Toimil-Molares, M. E., & Azzaroni, O. (2017). Bioinspired integrated nanosystems based on solid-state nanopores: «iontronic» transduction of biological, chemical and physical stimuli. Chemical Science, 8(2), 890-913. doi:10.1039/c6sc04255dGuo, W., Cao, L., Xia, J., Nie, F.-Q., Ma, W., Xue, J., … Jiang, L. (2010). Energy Harvesting with Single-Ion-Selective Nanopores: A Concentration-Gradient-Driven Nanofluidic Power Source. Advanced Functional Materials, 20(8), 1339-1344. doi:10.1002/adfm.200902312Roseman, J. M., Lin, J., Ramakrishnan, S., Rosenstein, J. K., & Shepard, K. L. (2015). Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nature Communications, 6(1). doi:10.1038/ncomms10070Kocer, A., Tauk, L., & Déjardin, P. (2012). Nanopore sensors: From hybrid to abiotic systems. Biosensors and Bioelectronics, 38(1), 1-10. doi:10.1016/j.bios.2012.05.013Maglia, G., Heron, A. J., Hwang, W. L., Holden, M. A., Mikhailova, E., Li, Q., … Bayley, H. (2009). Droplet networks with incorporated protein diodes show collective properties. Nature Nanotechnology, 4(7), 437-440. doi:10.1038/nnano.2009.121Han, J.-H., Kim, K. B., Kim, H. C., & Chung, T. D. (2009). Ionic Circuits Based on Polyelectrolyte Diodes on a Microchip. Angewandte Chemie International Edition, 48(21), 3830-3833. doi:10.1002/anie.200900045Ali, M., Ramirez, P., Nguyen, H. Q., Nasir, S., Cervera, J., Mafe, S., & Ensinger, W. (2012). Single Cigar-Shaped Nanopores Functionalized with Amphoteric Amino Acid Chains: Experimental and Theoretical Characterization. ACS Nano, 6(4), 3631-3640. doi:10.1021/nn3010119Vlassiouk, I., & Siwy, Z. S. (2007). Nanofluidic Diode. Nano Letters, 7(3), 552-556. doi:10.1021/nl062924bCervera, J., Ramirez, P., Mafe, S., & Stroeve, P. (2011). Asymmetric nanopore rectification for ion pumping, electrical power generation, and information processing applications. Electrochimica Acta, 56(12), 4504-4511. doi:10.1016/j.electacta.2011.02.056Ramírez, P., Rapp, H.-J., Mafé, S., & Bauer, B. (1994). Bipolar membranes under forward and reverse bias conditions. Theory vs. experiment. Journal of Electroanalytical Chemistry, 375(1-2), 101-108. doi:10.1016/0022-0728(94)03379-xHou, X., Guo, W., & Jiang, L. (2011). Biomimetic smart nanopores and nanochannels. Chemical Society Reviews, 40(5), 2385. doi:10.1039/c0cs00053aGuo, W., Tian, Y., & Jiang, L. (2013). Asymmetric Ion Transport through Ion-Channel-Mimetic Solid-State Nanopores. Accounts of Chemical Research, 46(12), 2834-2846. doi:10.1021/ar400024

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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Viabilidad técnica, económica y financiera de una botana de maíz cacahuacintle en Calimaya, Estado de México

Este trabajo muestra la metodología para el desarrollo de una botana de maíz cacahuacintle, así como el análisis financiero de su viabilidad comercial.En México los productores de maíz conservan este cultivo por razones sociales, económicas, culturales. A pesar de los varios decenios de mejoramiento genetico y la promoción de las variedades resultantes, gran parte de los productores mexicanos sigue sembrando las variedades locales de maíz (Keleman y Hellin, 2013: 3), por que las semillas criollas poseen mejores capacidades de adaptación a sequias, suelos pobres, condiciones climáticas extremas, e incluso pueden ser más resistentes a plagas y enfermedades (Perales et al. 2003). En el Estado de México más del 80% del área sembrada con maíz está cubierta por variedades criollas de este cereal. De acuerdo con las cifras del SIAP sugieren que cada año se producen casi 50.000 toneladas de grano de variedades para especialidades, incluyendo el maíz de colores (rojo, rosa o azul) y el pozolero (cacahuacintle) (Keleman y Hellin, 2013).Consejo Nacional de Ciencia y Tecnología Universidad Autónoma del Estado de Méxic