Home
Abstract
Hydrogels are essential in many fields ranging from tissue engineering and drug delivery to food sciences or cosmetics. Hydrogels that respond to specific biomolecular stimuli such as DNA, mRNA, miRNA and small molecules are highly desirable from the perspective of medical applications, however interfacing classical hydrogels with nucleic acids is still challenging. Here were demonstrate the generation of microbeads of DNA hydrogels with droplet microfluidic, and their morphological actuation with DNA strands. Using strand displacement and the specificity of DNA base pairing, we selectively dissolved gel beads, and reversibly changed their size on-the-fly with controlled swelling and shrinking. Lastly, we performed a complex computing primitive—A Winner-Takes-All competition between two populations of gel beads. Overall, these results show that strand responsive DNA gels have tantalizing potentials to enhance and expand traditional hydrogels, in particular for applications in sequencing and drug delivery.
Keywords: DNA nanotechnology; droplet microfluidic device; DNA hydrogels; toehold-strands; dynamic morphological transformation
Video
Table of Contents
Reference
[1] P. Bulpitt and D. Aeschlimann, “New Strategy for Chemical Modification of Hyaluronic Acid: Preparation of Functionalized Derivatives and Their Use in the Formation of Novel Biocompatible Hydrogels,” J. Biomed. Mater. Res., vol. 47, pp. 152–169, 1999.
[2] G. Molinaro, J. Leroux, J. Damas, and A. Adam, “Biocompatibility of thermosensitive chitosan-based hydrogels: An in vivo experimental approach to injectable biomaterials,” Biomaterials, vol. 23, pp. 2717–2722, 2002.
[3] K. Y. Lee and D. J. Mooney, “Hydrogels for Tissue Engineering,” Chem. Rev., vol. 101, pp. 1869–1880, 2001.
[4] S. Liu, P. Wang, G. Huang, L. Wang, J. Zhou, T. J. Lu, F. Xu, and M. Lin, “Reaction-induced swelling of ionic gels,” Soft Matter, vol. 11, pp. 449–455, 2015.
[5] J. Zhao, X. Zhao, B. Guo, and P. X. Ma, “Multifunctional Interpenetrating Polymer Network Hydrogels Based on Methacrylated Alginate for the Delivery of Small Molecule Drugs and Sustained Release of Protein,” Biomacromolecules, vol. 15, pp. 3246–3252, 2014.
[6] R. Hotta, L. S. Cheng, H. K. Graham, N. Nagy, J. Belkind-Gerson, G. Mattheolabakis, M. M. Amiji, and A. M. Goldstein, “Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo,” Biomaterials, vol. 88, pp. 1–11, 2016.
[7] X. Wang, W. E. Allen, M. Wright, E. L. Sylwestrak, N. Samusik, S. Vesuna, K. Evans, C. Liu, C. Ramakrishnan, J. Liu, et al., “Three-dimensional intact-tissue sequencing of single-cell transcriptional states,” Science, vol. 361, eaat5691, 2018.
[8] G. X. Y. Zheng, J. M. Terry, P. Belgrader, P. Ryvkin, Z. W. Bent, R. Wilson, S. B. Ziraldo, T. D. Wheeler, G. P. McDermott, J. Zhu, et al., “Massively parallel digital transcriptional profiling of single cells,” Nat. Commun., vol. 8, 14049, 2017.
[9] R. Zilionis, J. Nainys, A. Veres, V. Savova, D. Zemmour, A. M. Klein, and L. Mazutis, “Single-cell barcoding and sequencing using droplet microfluidics,” Nat. Protoc., vol. 12, pp. 44–73, 2017.
[10] Y. S. Kim, M. Liu, Y. Ishida, Y. Ebina, M. Osada, T. Sasaki, J. C. Hansen, M. Takata, and T. Aida, “Thermoresponsive actuation enabled by permittivity switching in an electrostatically anisotropic hydrogel,” Nat. Mater., vol. 14, pp. 1002–1007, 2015.
[11] Q. Shi, H. Liu, D. Tang, Y. Li, X. Li, and F. Xu, “Bioactuators based on stimulus-responsive hydrogels and their emerging biomedical applications,” NPG Asia Mater., vol. 11, pp. 1–21, 2019.
[12] J.-P. Chen and T.-H. Cheng, “Thermo-Responsive Chitosan-graft-poly(N-isopropylacrylamide) Injectable Hydrogel for Cultivation of Chondrocytes and Meniscus Cells,” Macromol. Biosci., vol. 6, pp. 1026–1039, 2006.
[13] D. J. Beebe, J. S. Moore, J. M. Bauer, Q. Yu, R. H. Liu, C. Devadoss, and B.-H. Jo, “Functional hydrogel structures for autonomous flow control inside microfluidic channels,” Nat. Cell Biol., vol. 404, pp. 588–590, 2000.
[14] H. Nakagawa, Y. Hara, S. Maeda, and S. Hashimoto, “A Pendulum-Like Motion of Nanofiber Gel Actuator Synchronized with External Periodic pH Oscillation,” Polymers, vol. 3, pp. 405–412, 2011.
[15] R. Yoshida, K. Uchida, Y. Kaneko, K. Sakai, A. Kikuchi, Y. Sakurai, and T. Okano, “Comb-type grafted hydrogels with rapid deswelling response to temperature changes,” Nat. Cell Biol., vol. 374, pp. 240–242, 1995.
[16] L. Hao, C. Yegin, J. V. Talari, J. K. Oh, M. Zhang, M. M. Sari, L. Zhang, Y. Min, M. Akbulut, and B. Bin Jiang, “Thermo-responsive gels based on supramolecular assembly of an amidoamine and citric acid,” Soft Matter, vol. 14, pp. 432–439, 2018.
[17] R. Zhong, M. Xiao, C. Zhu, X. Shen, Q. Tang, W. Zhang, L. Wang, S. Song, X. Qu, H. Pei, et al., “Logic Catalytic Interconversion of G-Molecular Hydrogel,” ACS Appl. Mater. Interfaces, vol. 10, pp. 4512–4518, 2018.
[18] R. Zhong, Q. Tang, S. Wang, H. Zhang, F. Zhang, M. Xiao, T. Man, X. Qu, L. Li, W. Zhang, et al., “Self-Assembly of Enzyme-Like Nanofibrous G-Molecular Hydrogel for Printed Flexible Electrochemical Sensors,” Adv. Mater., vol. 30, e1706887, 2018.
[19] S. J. Kim, H. I. Kim, S. J. Park, I. Y. Kim, S. H. Lee, T. S. I. Lee, and S. Kim, “Behavior in electric fields of smart hydrogels with potential application as bio-inspired actuators,” Smart Mater. Struct., vol. 14, pp. 511–514, 2005.
[20] E. Wang, M. S. Desai, and S.-W. Lee, “Light-Controlled Graphene-Elastin Composite Hydrogel Actuators,” Nano Lett., vol. 13, pp. 2826–2830, 2013.
[21] C. Keplinger, J.-Y. Sun, C. C. Foo, P. Rothemund, G. M. Whitesides, and Z. Suo, “Stretchable, Transparent, Ionic Conductors,” Science, vol. 341, pp. 984–987, 2013.
[22] S. Kidoaki and T. Matsuda, “Microelastic gradient gelatinous gels to induce cellular mechanotaxis,” J. Biotechnol., vol. 133, pp. 225–230, 2008.
[23] T. Kawano and S. Kidoaki, “Elasticity boundary conditions required for cell mechanotaxis on microelastically-patterned gels,” Biomaterials, vol. 32, pp. 2725–2733, 2011.
[24] Y.-W. Kang, J. Woo, H.-R. Lee, and J.-Y. Sun, “A mechanically enhanced electroactive hydrogel for 3D printing using a multileg long chain crosslinker,” Smart Mater. Struct., vol. 28, 095016, 2019.
[25] C. Cvetkovic, R. Raman, V. Chan, B. J. Williams, M. Tolish, P. Bajaj, M. S. Sakar, H. H. Asada, M. T. A. Saif, and R. Bashir, “Three-dimensionally printed biological machines powered by skeletal muscle,” Proc. Natl. Acad. Sci. USA, vol. 111, pp. 10125–10130, 2014.
[26] Y. Zhao, X. Zhao, B. Tang, W. Xu, J. Li, J. Hu, and Z. Gu, “Quantum-Dot-Tagged Bioresponsive Hydrogel Suspension Array for Multiplex Label-Free DNA Detection,” Adv. Funct. Mater., vol. 20, pp. 976–982, 2010.
[27] J. Oliveira and R. Reis, “Hydrogels from polysaccharide-based materials: Fundamentals and applications in regenerative medicine,” in Natural-Based Polymers for Biomedical Applications, Elsevier BV: Amsterdam, The Netherlands, pp. 485–514, 2008.
[28] J. Sun and H. Tan, “Alginate-Based Biomaterials for Regenerative Medicine Applications,” Materials, vol. 6, pp. 1285–1309, 2013.
[29] B. Bai, J. Zhou, and M. Yin, “A comprehensive review of polyacrylamide polymer gels for conformance control,” Pet. Explor. Dev., vol. 42, pp. 525–532, 2015.
[30] X. Xu, A. K. Jha, D. A. Harrington, M. C. Farach-Carson, and X. Jia, “Hyaluronic acid-based hydrogels: From a natural polysaccharide to complex networks,” Soft Matter, vol. 8, pp. 3280–3294, 2012.
[31] M. Shibayama, X. Li, and T. Sakai, “Precision polymer network science with tetra-PEG gels—A decade history and future,” Colloid Polym. Sci., vol. 297, pp. 1–12, 2019.
[32] W. Guo, C.-H. Lu, X.-J. Qi, R. Orbach, M. Fadeev, H.-H. Yang, and I. Willner, “Switchable Bifunctional Stimuli-Triggered Poly-N-Isopropylacrylamide/DNA Hydrogels,” Angew. Chem. Int. Ed., vol. 53, pp. 10134–10138, 2014.
[33] E. Cheng, Y. Xing, P. Chen, Y. Yang, Y. Sun, D. Zhou, L. Xu, Q. Fan, and D. Liu, “A pH-Triggered, Fast-Responding DNA Hydrogel,” Angew. Chem. Int. Ed., vol. 48, pp. 7660–7663, 2009.
[34] W. Guo, C.-H. Lu, R. Orbach, F. Wang, X.-J. Qi, A. Cecconello, D. Seliktar, and I. Willner, “pH-Stimulated DNA Hydrogels Exhibiting Shape-Memory Properties,” Adv. Mater., vol. 27, pp. 73–78, 2015.
[35] Y. Xing, E. Cheng, Y. Yang, P. Chen, T. Zhang, Y. Sun, Z. Yang, and D. Liu, “Self-Assembled DNA Hydrogels with Designable Thermal and Enzymatic Responsiveness,” Adv. Mater., vol. 23, pp. 1117–1121, 2010.
[36] P. W. K. Rothemund, “Folding DNA to create nanoscale shapes and patterns,” Nat. Cell Biol., vol. 440, pp. 297–302, 2006.
[37] S. M. Douglas, H. Dietz, T. Liedl, B. Högberg, F. Graf, and W. M. Shih, “Self-assembly of DNA into nanoscale three-dimensional shapes,” Nat. Cell Biol., vol. 459, pp. 414–418, 2009.
[38] D. Han, S. Pal, J. Nangreave, Z. Deng, Y. Liu, and H. Yan, “DNA Origami with Complex Curvatures in Three-Dimensional Space,” Science, vol. 332, pp. 342–346, 2011.
[39] Y. Sato, T. Sakamoto, and M. Takinoue, “Sequence-based engineering of dynamic functions of micrometer-sized DNA droplets,” Sci. Adv., vol. 6, eaba3471, 2020.
[40] M. D. Frank-Kamenetskiĭ, V. V. Anshelevich, and A. V. Lukashin, “Polyelectrolyte model of DNA,” Sov. Phys. Uspekhi, vol. 30, pp. 317–330, 1987.
[41] S. H. Um, J. B. Lee, N. Park, S. Y. Kwon, C. C. Umbach, and D. Luo, “Enzyme-catalysed assembly of DNA hydrogel,” Nat. Mater., vol. 5, pp. 797–801, 2006.
[42] K. Gehring, J.-L. Leroy, and M. Guéron, “A tetrameric DNA structure with protonated cytosine-cytosine base pairs,” Nat. Cell Biol., vol. 363, pp. 561–565, 1993.
[43] Y. Murakami and M. Maeda, “DNA-Responsive Hydrogels That Can Shrink or Swell,” Biomacromolecules, vol. 6, pp. 2927–2929, 2005.
[44] P. Song, D. Ye, X. Zuo, J. Li, J. Wang, H. Liu, M. T. Hwang, J. Chao, S. Su, L. Wang, et al., “DNA Hydrogel with Aptamer-Toehold-Based Recognition, Cloaking, and Decloaking of Circulating Tumor Cells for Live Cell Analysis,” Nano Lett., vol. 17, pp. 5193–5198, 2017.
[45] W. Choi, S. Y. Yeom, J. Kim, S. Jung, S. Jung, T. S. Shim, S. K. Kim, J. Y. Kang, S. H. Lee, I.-J. Cho, et al., “Hydrogel micropost-based qPCR for multiplex detection of miRNAs associated with Alzheimer’s disease,” Biosens. Bioelectron., vol. 101, pp. 235–244, 2018.
[46] M. R. Hartman, D. Yang, T. N. N. Tran, K. Lee, J. S. Kahn, P. Kiatwuthinon, K. G. Yancey, O. Trotsenko, S. Minko, and D. Luo, “Thermostable Branched DNA Nanostructures as Modular Primers for Polymerase Chain Reaction,” Angew. Chem. Int. Ed., vol. 52, pp. 8699–8702, 2013.
[47] C. Li, A. Faulkner-Jones, A. R. Dun, J. Jin, P. Chen, Y. Xing, Z. Yang, Z. Li, W. Shu, D. Liu, et al., “Rapid Formation of a Supramolecular Polypeptide-DNA Hydrogel for In Situ Three-Dimensional Multilayer Bioprinting,” Angew. Chem. Int. Ed., vol. 54, pp. 3957–3961, 2015.
[48] M. A. English, L. R. Soenksen, R. V. Gayet, H. de Puig, N. M. Angenent-Mari, A. S. Mao, P. Q. Nguyen, and J. J. Collins, “Programmable CRISPR-responsive smart materials,” Science, vol. 365, pp. 780–785, 2019.
[49] S. Xu, Z. Nie, M. Seo, P. Lewis, E. Kumacheva, H. A. Stone, P. Garstecki, D. B. Weibel, I. Gitlin, and G. M. Whitesides, “Generation of Monodisperse Particles by Using Microfluidics: Control over Size, Shape, and Composition,” Angew. Chem., vol. 117, pp. 734–738, 2005.
[50] A. C. Daly, L. Riley, T. Segura, and J. A. Burdick, “Hydrogel microparticles for biomedical applications,” Nat. Rev. Mater., vol. 5, pp. 20–43, 2020.
[51] L. Desbois, A. Padirac, S. Kaneda, A. J. Genot, Y. Rondelez, D. Hober, D. Collard, and T. Fujii, “A microfluidic device for on-chip agarose microbead generation with ultralow reagent consumption,” Biomicrofluidics, vol. 6, 44101, 2012.
[52] S. Yadavali, H.-H. Jeong, S. H. Lee, and D. Issadore, “Silicon and glass very large-scale microfluidic droplet integration for terascale generation of polymer microparticles,” Nat. Commun., vol. 9, 1222, 2018.
[53] V. Yelleswarapu, J. R. Buser, M. Haber, J. Baron, E. Inapuri, and D. Issadore, “Mobile platform for rapid sub–picogram-per-milliliter, multiplexed, digital droplet detection of proteins,” Proc. Natl. Acad. Sci. USA, vol. 116, pp. 4489–4495, 2019.
[54] J. M. de Rutte, D. di Carlo, and D. di Carlo, “Scalable High-Throughput Production of Modular Microgels for In Situ Assembly of Microporous Tissue Scaffolds,” Adv. Funct. Mater., vol. 29, 1900071, 2019.
[55] J. E. Mealy, J. J. Chung, H.-H. Jeong, D. Issadore, S. H. Lee, P. Atluri, and J. A. Burdick, “Injectable Granular Hydrogels with Multifunctional Properties for Biomedical Applications,” Adv. Mater., vol. 30, e1705912, 2018.
[56] A. S. Caldwell, G. T. Campbell, K. M. T. Shekiro, and K. S. Anseth, “Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation,” Adv. Healthc. Mater., vol. 6, 2017.
[57] D. R. Griffin, W. M. Weaver, P. O. Scumpia, D. di Carlo, and T. Segura, “Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks,” Nat. Mater., vol. 14, pp. 737–744, 2015.
[58] R. J. Wade, E. J. Bassin, C. B. Rodell, and J. A. Burdick, “Protease-degradable electrospun fibrous hydrogels,” Nat. Commun., vol. 6, pp. 1–10, 2015.
[59] C. B. Highley, K. H. Song, A. C. Daly, and J. A. Burdick, “Jammed Microgel Inks for 3D Printing Applications,” Adv. Sci., vol. 6, 1801076, 2019.
[60] S. Yoshida, M. Takinoue, E. Iwase, and H. Onoe, “Dynamic transformation of self-assembled structures using anisotropic magnetized hydrogel microparticles,” J. Appl. Phys., vol. 120, 084905, 2016.
[61] M. Hayakawa, S. Umeyama, K. Nagai, H. Onoe, and M. Takinoue, “Controlled Construction of Stable Network Structure Composed of Honeycomb-Shaped Microhydrogels,” Life, vol. 8, 38, 2018.
[62] B. Yurke, A. J. Turberfield, A. P. Mills, F. C. Simmel, and J. L. Neumann, “A DNA-fuelled molecular machine made of DNA,” Nat. Cell Biol., vol. 406, pp. 605–608, 2000.
[63] A. J. Genot, D. Y. Zhang, J. Bath, and A. J. Turberfield, “Remote Toehold: A Mechanism for Flexible Control of DNA Hybridization Kinetics,” J. Am. Chem. Soc., vol. 133, pp. 2177–2182, 2011.
[64] A. J. Genot, J. Bath, and A. J. Turberfield, “Combinatorial Displacement of DNA Strands: Application to Matrix Multiplication and Weighted Sums,” Angew. Chem. Int. Ed., vol. 52, pp. 1189–1192, 2012.
[65] X. Chen, “Expanding the Rule Set of DNA Circuitry with Associative Toehold Activation,” J. Am. Chem. Soc., vol. 134, pp. 263–271, 2011.
[66] “A Mechanism for Gene Conversion in Fungi | Genetics Research | Cambridge Core,” Available online: https://www.cambridge.org/core/journals/genetics-research/article/mechanism-for-gene-conversion-in-fungi/E11586A6605C2A54C648BACEABECF954 (accessed on 1 December 2020).
[67] T. Elshaarani, H. Yu, L. Wang, J. Feng, C. Li, W. Zhou, A. Khan, M. Usman, B. U. Amin, and R. Khan, “Chitosan reinforced hydrogels with swelling-shrinking behaviors in response to glucose concentration,” Int. J. Biol. Macromol., vol. 161, pp. 109–121, 2020.
[68] A. Cangialosi, C. Yoon, J. Liu, Q. Huang, J. Guo, T. D. Nguyen, D. H. Gracias, and R. Schulman, “DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling,” Science, vol. 357, pp. 1126–1130, 2017.
[69] A. J. Genot, A. Baccouche, R. Sieskind, N. Aubert-Kato, N. Bredeche, J. F. Bartolo, V. Taly, T. Fujii, and Y. Rondelez, “High-resolution mapping of bifurcations in nonlinear biochemical circuits,” Nat. Chem., vol. 8, pp. 760–767, 2016.
[70] A. Baccouche, S. Okumura, R. Sieskind, E. Henry, N. Aubert-Kato, N. Bredeche, J.-F. Bartolo, V. Taly, Y. Rondelez, T. Fujii, et al., “Massively parallel and multiparameter titration of biochemical assays with droplet microfluidics,” Nat. Protoc., vol. 12, pp. 1912–1932, 2017.
[71] S. K. Sia and G. M. Whitesides, “Microfluidic devices fabricated in Poly(dimethylsiloxane) for biological studies,” Electrophoresis, vol. 24, pp. 3563–3576, 2003.
[72] D. Kandatsu, K. Cervantes-Salguero, I. Kawamata, S. Hamada, S.-I. M. Nomura, K. Fujimoto, and S. Murata, “Reversible Gel-Sol Transition of a Photo-Responsive DNA Gel,” ChemBioChem, vol. 17, pp. 1118–1121, 2016.
[73] M. Hiraide, K. Ishikawa, and H. Kawaguchi, “Water-in-oil emulsion containing oxine for the collection of traces of copper(II) in water,” Anal. Bioanal. Chem., vol. 356, pp. 155–158, 1996.
[74] M. Schmitt, S. Limage, R. Denoyel, and M. Antoni, “Effect of SPAN80 on the structure of emulsified aqueous suspensions,” Colloids Surfaces A Physicochem. Eng. Asp., vol. 521, pp. 121–132, 2017.
[75] Z. Xing, A. Caciagli, T. Cao, I. Stoev, M. Zupkauskas, T. O’Neill, T. Wenzel, R. Lamboll, D. Liu, and E. Eiser, “Microrheology of DNA hydrogels,” Proc. Natl. Acad. Sci. USA, vol. 115, pp. 8137–8142, 2018.
[76] N. C. Seeman, “Nucleic acid junctions and lattices,” J. Theor. Biol., vol. 99, pp. 237–247, 1982.
[77] K. M. Cherry and L. Qian, “Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks,” Nat. Cell Biol., vol. 559, pp. 370–376, 2018.
[78] K. Gaweł, D. Barriet, M. Sletmoen, and B. T. Stokke, “Responsive Hydrogels for Label-Free Signal Transduction within Biosensors,” Sensors, vol. 10, pp. 4381–4409, 2010.
[79] C. Jiang, X. Li, H. Zhao, and H. Liu, “Long non-coding RNAs: Potential new biomarkers for predicting tumor invasion and metastasis,” Mol. Cancer, vol. 15, pp. 1–15, 2016.
[80] M. Klingenberg, A. Matsuda, S. Diederichs, and T. Patel, “Non-coding RNA in hepatocellular carcinoma: Mechanisms, biomarkers and therapeutic targets,” J. Hepatol., vol. 67, pp. 603–618, 2017.
[81] Z. Peng, C. Liu, and M. Wu, “New insights into long noncoding RNAs and their roles in glioma,” Mol. Cancer, vol. 17, pp. 1–10, 2018.
[82] A. Charles, J. Janeway, P. Travers, M. Walport, and M. J. Shlomchik, “The Structure of a Typical Antibody Molecule,” in Immunobiology: The Immune System in Health and Disease, 5th ed., NCBI: Bethesda, MD, USA, 2001.
[83] T. Miyata, A. N. Asami, and T. Uragami, “Preparation of an Antigen-Sensitive Hydrogel Using Antigen−Antibody Bindings,” Macromolecules, vol. 32, pp. 2082–2084, 1999.
[84] P. T. Charles, E. R. Goldman, J. G. Rangasammy, C. L. Schauer, M.-S. Chen, and C. R. Taitt, “Fabrication and characterization of 3D hydrogel microarrays to measure antigenicity and antibody functionality for biosensor applications,” Biosens. Bioelectron., vol. 20, pp. 753–764, 2004.
[85] T. Miyata, N. Asami, and T. Uragami, “A reversibly antigen-responsive hydrogel,” Nat. Cell Biol., vol. 399, pp. 766–769, 1999.
[86] T. J. Bartosh, J. H. Ylöstalo, A. Mohammadipoor, N. Bazhanov, K. Coble, K. Claypool, R. H. Lee, H. Choi, and D. J. Prockop, “Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties,” Proc. Natl. Acad. Sci. USA, vol. 107, pp. 13724–13729, 2010.
[87] R. F.-X. Tomasi, S. Sart, T. Champetier, and C. N. Baroud, “Individual Control and Quantification of 3D Spheroids in a High-Density Microfluidic Droplet Array,” Cell Rep., vol. 31, 107670, 2020.
[88] S. Sart, R. F.-X. Tomasi, G. Amselem, and C. N. Baroud, “Multiscale cytometry and regulation of 3D cell cultures on a chip,” Nat. Commun., vol. 8, pp. 1–13, 2017.
