Featured recent publications:
Full list of our publications can be found at Google Scholar
- SE Cassel, B Huntington, W Chen, P Lei, S Andreadis, AM Kloxin, “Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations,” APL Bioengineering, 8, 2, 2024. DOI: 10.1063/5.0166152
- J Graf, K Bomb, M Trautmann-Rodriguez, BM Jarai, N Gill, AM Kloxin, CA Fromen, “Macrophage variance: investigating how macrophage origin influences responses to soluble and physical cues with immortalized vs. primary cells in 2D and 3D culture,” Frontiers in Biomaterials Science, 3, 2024. DOI: 10.3389/fbiom.2024.1399448
- AL Lopez-Ruiz, ED Slaughter, AM Kloxin, CA Fromen, “Bridging the gender gap in autoimmunity with T-cell-targeted biomaterials,” Current Opinion in Biotechnology, 86, 103075, 2024. DOI: 10.1016/j.copbio.2024.103075
- LL Palmese, PJ LeValley, L Pradhan, AL Parsons, JS Oakey, M Abraham, SM D’Addio, AM Kloxin, Y Liang, KL Kiick, “Injectable liposome-containing click hydrogel microparticles for release of macromolecular cargos,” Soft Matter, 20, 1736-175, 2024. DOI: 10.1039/D3SM01009K
- J Graf, M Trautmann-Rodriguez, S Sabnis, AM Kloxin, CA Fromen, “On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI),” European Journal of Pharmaceutical Sciences, 191, 106596, 2023. DOI: 10.1016/j.ejps.2023.106596
- PA Taylor, S Kroneberger, AM Kloxin, A Jayaraman, “Effects of solvent conditions on the self-assembly of heterotrimeric collagen-like peptide (CLP) triple helices: a coarse-grained simulation study,” Soft Matter, 12, 725-732, 2023. DOI: 10.1039/D3SM00374D
- K Bomb, Q Zhang, EM Ford, CA Fromen, AM Kloxin, “Systematic D-amino acid substitutions to control peptide and hydrogel degradation in cellular microenvironments, ACS Macro Letters, 12, 725-732, 2023. DOI: 10.1021/acsmacrolett.3c00144
- L Pradhan, DV Moore, EM Ovadia, SL Swedzinski, T Cossette, RA Sikes, K van Golen, AM Kloxin, “Dynamic bioinspired coculture model for probing ER+ breast cancer dormancy in the bone marrow niche,” Science Advances, 9 (10), eade3186, 2023. DOI: 10.1126/sciadv.ade3186
- KA Wodzanowski, MV Anonick, LA Genova, AM Kloxin, CL Grimes, “Bringing Pasteur Back to Life: Studying the Biochemistry of Yeast Fermentation Through Discussion Groups and an At-Home Lab,” CourseSource, 10, 2023. DOI: 10.24918/cs.2023.11
- K Bomb, PJ LeValley, IR Woodward, SE Cassel, BP Sutherland, A Bhattacharjee, Z Yun, J Steen, E Kurdzo, J McCoskey, D Burris, K Levine, C Carbrello, AM Lenhoff, CA Fromen, AM Kloxin, “Cell Therapy Biomanufacturing: Integrating Biomaterial and Flow‐Based Membrane Technologies for Production of Engineered T‐Cells,” Advanced Materials Technologies, 2201155, 2023. DOI: 10.1002/admt.202201155
- K Bomb, L Pradhan, Q Zhang, BM Jarai, A Bhattacharjee, D Burris, AM Kloxin, CA Fromen, “Destructive fibrotic teamwork: how both microenvironment stiffness and profibrotic interleukin 13 impair alveolar macrophage phenotype and function,” Biomaterials Science, 10, 5689-5706, 2022. DOI: 10.1039/d2bm00828a
- U Blache, EM Ford, B Ha, L Rijns, O Chaudhuri, PYW Dankers, AM Kloxin, JG Snedeker, E Gentleman, “Engineered hydrogels for mechanobiology,” Nature Reviews Methods Primers, 2, 98, 2022. DOI: 10.1038/s43586-022-00179-7
- PJ LeValley, AL Parsons, BP Sutherland, KL Kiick, JS Oakey, AM Kloxin, “Microgels Formed by Spontaneous Click Chemistries Utilizing Microfluidic Flow Focusing for Cargo Release in Response to Endogenous or Exogenous Stimuli,” Pharmaceutics, 14, 1062, 2022. https://doi.org/10.3390/pharmaceutics14051062
- PA Taylor, AM Kloxin, A Jayaraman, “Impact of collagen-like peptide (CLP) heterotrimeric triple helix design on helical thermal stability and hierarchical assembly: A coarse-grained molecular dynamics simulation study,” Soft Matter, 18, 3177-3192, 2022. DOI: 10.1039/D2SM00087C
- AP Liu, EA Appel, PD Ashby, BM Baker, E Franco, L Gu, K Haynes, NS Joshi, AM Kloxin, PHJ Kouwer, J Mittal, L Morsut, V Noireaux, S Parekh, R Schulman, SKY Tang, MT Valentine, SL Vega, W Weber, N Stephanopoulos, O Chaudhuri, “The ‘living interface’: a bridge between synthetic biology and biomaterials,” Nature Materials, 21, 390-397, 2022. DOI: 0.1038/s41563-022-01231-3
- KA Wodzanowski, JL Caplan, AM Kloxin, CL Grimes, “Multiscale Invasion Assay for Probing Macrophage Response to Gram-Negative Bacteria,” Frontiers in Chemistry, 10, 2022
- KL Wiley, BP Sutherland, BA Ogunnaike, AM Kloxin, “Rational design of hydrogel networks with dynamic mechanical properties to mimic matrix remodeling,” Advanced Healthcare Materials, 11, 2101947, 2021. DOI: 10.1002/adhm.202101947
- M Rabionet; E Polonio-Alcala; J Relat; M Yeste; J Sims-Mourtada; AM Kloxin; M Planas; L Feliu; J Ciurana; T Puig, “Fatty acid synthase as a feasible biomarker for triple negative breast cancer stem cell subpopulation cultured on electrospun scaffolds,” Materials Today Bio, 12, 100155, 2021. DOI: 10.1016/j.mtbio.2021.100155
- EM Ford, AM Kloxin, “Rapid production of multifunctional self-assembling peptides for incorporation and visualization within hydrogel biomaterials,” ACS Biomaterials Science & Engineering, 7, 4175-4195, 2021. DOI: 10.1021/acsbiomaterials.1c00589
- AM Hilderbrand, PA Taylor, F Stanzione, M Larue, C Guo, A Jayaraman, AM Kloxin, “Combining simulations and experiments for the molecular engineering of multifunctional collagen mimetic peptide-based materials,” Soft Matter, 17, 1985-1998, 2021. DOI:10.1039/d0sm01562h
- BM Jarai, Z Stillman, K Bomb, AM Kloxin, CA Fromen, “Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19,” ACS Biomaterials Science & Engineering, 7, 1742-1764, 2021. doi:10.1021/acsbiomaterials.0c01287
- T Sulerud, AB Sami, G Li, A Kloxin, J Oakey, J Gatlin, “Microtubule-dependent pushing forces contribute to long-distance aster movement and centration in Xenopus laevis egg extracts,” Molecular Biology of the Cell, 31, 2791–2802, 2020. DOI:10.1091/mbc.e20-01-0088
- RC Locke, EM Ford, KG Silbernagel, AM Kloxin, ML Killian, “Success criteria and preclinical testing of multifunctional hydrogels for tendon regeneration,” Tissue Engineering Part C: Methods, 26, 10, 506-518, 2020. DOI: 10.1089/ten.tec.2020.0199
- PJ LeValley, BO Sutherland, J Jaje, S Gibbs, M Jones, R Gala, CJ Kloxin, KL Kiick, AM Kloxin, “On-demand and tunable dual wavelength release of antibodies using light-responsive hydrogels,” ACS Applied Bio Materials,3, 10, 6944-6958, 2020. DOI: 10.1021/acsabm.0c00823
- BP Sutherland, PJ LeValley, DJ Bischoff, AM Kloxin, CJ Kloxin, “Sequence-defined vinyl sulfonamide click nucleic acids (VS-CNAs) and their assembly into dynamically responsive materials,” Chemical Communications, 56, 11263-11266, 2020. DOI: 10.1039/D0CC04235H
- EM Ovadia, L Pradhan, LA Sawicki, JE Cowart, RE Huber, SW Polson, C Chen, KL van Golen, KE Ross, CH Wu, AM Kloxin, “Understanding ER+ Breast Cancer Dormancy using Bioinspired Synthetic Matrices for Long-term 3D Culture and Insights into Late Recurrence,” Advanced Biosystems, 4, 9, 2000119, 2020. DOI: 10.1002/adbi.202000119
- SJ Ma, EM Ford, LA Sawicki, BP Sutherland, NI Halaszynski, BJ Carberry, NJ Wagner, AM Kloxin, CJ Kloxin,“Surface Chemical Functionalization of Wrinkled Thiol–Ene Elastomers for Promoting Cellular Alignment,”ACS Applied Bio Materials, 3, 6, 3731-3740, 2020. DOI: 10.1021/acsabm.0c00346
- KA Wodzanowski, SE Cassel, CL Grimes, AM Kloxin, “Tools for probing host-bacteria interactions in the gut microenvironment: from molecular to cellular levels,” Bioorganic & Medicinal Chemistry Letters, 30, 10, 127116, 2020
- PJ LeValley, R Neelarapu, BP Sutherland, S Dasgupta, CJ Kloxin, AM Kloxin, “Photolabile Linkers: Exploiting labile bond chemistry to control mode and rate of hydrogel degradation and protein release,” Journal of the American Chemical Society, 142, 10, 4671-4679, 2020. DOI: 10.1021/jacs.9b11564
- AM Hilderbrand, EM Ford, C Guo, JD Sloppy, AM Kloxin, “Hierarchically structured hydrogels utilizing multifunctional assembling peptides for 3D cell culture,” Biomaterials Science, 8, 1256-1269, 2020. DOI: 10.1039/C9BM01894H
- AI Marusina, AA Merleev, JI Luna, L Olney, NE Haigh, D Yoon, C Guo, EM Ovadia, M Shimoda, G Luxardi, S Boddu, NN Lal, Y Takada, KS Lam, R Liu, RR Isseroff, S Le, JA Nolta, AM Kloxin^, Emanual Maverakis^, “Tunable hydrogels for mesenchymal stem cell delivery: Integrin-induced transcriptome alterations and hydrogel optimization for human wound healing,” Stem Cells, 38, 231-245, 2020. DOI: 10.1002/stem.3105
- ME Smithmyer, SE Cassel, AM Kloxin, “Bridging 2D and 3D culture: Probing impact of extracellular environment on fibroblast activation in layered hydrogels,” AIChE J, 65, e16837, 2019. DOI:10.1002/aic.16837
- J Bisht, PJ LeValley, B Noren, R McBride, PM Kharkar, AM Kloxin, J Gatlin, and J Oakey, “Light-Inducible Activation of Cell Cycle Progression in Xenopus Egg Extracts Under Microfluidic Confinement,” Lab on a Chip, 19, 3499-3511, 2019. DOI: 10.1039/C9LC00569B
- KL Wiley, EM Ovadia, CJ Calo, RE Huber, AM Kloxin, “Rate-based approach for controlling the mechanical properties of ‘thiol-ene’ hydrogels formed with visible light,” Polymer Chemistry, 10, 4428-4440, 2019. DOI: 10.1039/C9PY00447E
- LA Sawicki, EM Ovadia, L Pradhan, JE Cowart, KE Ross, CH Wu, AM Kloxin, “Tunable synthetic extracellular matrices to investigate breast cancer response to biophysical and biochemical cues,” APL Bioengineering, 3, 016101, 2019. DOI: 10.1063/1.5064596
- PJ LeValley, AM Kloxin, “Chemical Approaches to Dynamically Modulate the Properties of Synthetic Matrices,” ACS Macro Letters, 8, 7-16, 2019. DOI: 10.1021/acsmacrolett.8b00808
- PJ LeValley, MW Tibbitt, B Noren, PM Kharkar, AM Kloxin, KS Anseth, M Toner, J Oakey “Immunofunctional photodegradable poly(ethylene glycol) hydrogel surfaces for the capture and release of rare cells,” Colloids and Surfaces B: Biointerfaces, 174, 483-492, 2019. DOI: 10.1016/j.colsurfb.2018.11.049
- H Wu, PJ LeValley, T, Luo, AM Kloxin, KL Kiick, “Manipulation of Glutathione-Mediated Degradation of Thiol-Maleimide Conjugates,” Bioconjugate Chemistry, 29, 3595-3605, 2018. DOI: 10.1021/acs.bioconjchem.8b00546
- ME Smithmyer, CC Deng, SE Cassel, PJ LeValley, BS Sumerlin, AM Kloxin, “Self-healing boronic acid-based hydrogels for 3D co-cultures,” ACS Macro Letters, 7, 1105-1110, 2018. DOI: 10.1021/acsmacrolett.8b00462
- ME Smithmyer, JB Spohn, AM Kloxin, “Probing fibroblast activation in response to extracellular matrix cues with well-defined culture platform,” ACS Biomaterials Science & Engineering, 4, 3304-3316, 2018. DOI: 10.1021/acsbiomaterials.8b00491
- PJ LeValley, B Noren, PM Kharkar, AM Kloxin, JC Gatlin, J Oakey, “Fabrication of Functional Biomaterial Microstructures by in Situ Photopolymerization and Photodegradation,” ACS Biomaterials Science & Engineering, 4, 3078-3087, 2018. DOI: 10.1021/acsbiomaterials.8b00350
- PJ LeValley, EO Ovadia, CA Bresette, LA Sawicki, E Maverakis, S Bai, AM Kloxin, “Design of functionalized cyclic peptides through orthogonal click reactions for cell culture and targeting applications,” Chemical Communications, 54, 6923-6926, 2018. DOI: 10.1039/C8CC03218A
- LJ Macdougall, KL Wiley, AM Kloxin, AP Dove, “Design of Synthetic Extracellular Matrices for Probing Breast Cancer Cell Growth Using Robust Cytocompatible Nucleophilic Thiol-yne Addition Chemistry,” Biomaterials, 178, 435-447, 2018. DOI: 10.1016/j.biomaterials.2018.04.046
- EO Ovadia, DW Colby, AM Kloxin, “Designing photopolymerized synthetic matrices for three-dimensional culture and differentiation of induced pluripotent stem cells,” Biomaterials Science, 6, 1358-1370, 2018. DOI: 10.1039/c8bm00099a
- NJ Smith, K Rohlfing, LA Sawicki, PM Kharkar, SJ Boyd, AM Kloxin, JM Fox, “Fast, Irreversible Modification of Cysteines through Strain Releasing Conjugate Additions of Cyclopropenyl Ketones,” Organic & Biomolecular Chemistry, 16, 2164-2169, 2018. DOI: 10.1039/C8OB00166A
- LA Sawicki, LH Choe, KL Wiley, KH Lee, AM Kloxin, “Isolation and identification of proteins secreted by cells cultured within synthetic hydrogel-based matrices,” ACS Biomaterials Science and Engineering, 4, 836-845, 2018. DOI: 10.1021/acsbiomaterials.7b00647
- MS Rehmann, KM Skeens, PM Kharkar, EM Ford, E Maverakis, KH Lee, AM Kloxin, “Tuning and predicting mesh size and protein release from step growth hydrogels,” Biomacromolecules, 18,3131-3142, 2017.DOI: 10.1021/acs.biomac.7b00781
- PM Kharkar, RA Scott, LP Olney, PF Levalley, E Maverakis, KL Kiick, AM Kloxin, “Controlling the release of small, bioactive proteins via dual mechanisms with therapeutic potential,” Advanced Healthcare Materials, 6, 1700713, 2017. DOI: 10.1002/adhm.201700713
- C Guo, H Kim, EM Ovadia, CM Mourafetis, M Yang, W Chen, AM Kloxin, “Bio-orthogonal conjugation and enzymatically triggered release of proteins within multi-layered hydrogels,” Acta Biomaterialia, 56, 80-90, 2017. DOI: 10.1016/j.actbio.2017.04.002
- LA Sawicki, AM Kloxin, “Light-mediated Formation and Patterning of Hydrogels for Cell Culture Applications,” Journal of Visual Experiments (115), e54462,2016. DOI: 10.3791/54462
- AM Hilderbrand, EM Ovadia, MS Rehmann, PM Kharkar, C Guo, AM Kloxin, “Biomaterials for 4D stem cell culture,” Current Opinion in Solid State Materials, 20, 212-224, 2016. DOI: 10.1016/j.cossms.2016.03.002
- MS Rehmann, JI Luna, E Maverakis, AM Kloxin, “Tuning microenvironment modulus and biochemical composition promotes human mesenchymal stem cell tenogenic differentiation,” Journal of Biomedical Materials Research Part A, 104, 1162–1174, 2016. DOI: 10.1002/jbm.a.35650
- PM Kharkar, MS Rehmann, KM Skeens, E Maverakis, AM Kloxin, “Thiol–ene click hydrogels for therapeutic delivery,” ACS Biomaterials Science and Engineering, 2, 165–179, 2016. DOI:10.1021/acsbiomaterials.5b00420
- PM Kharkar, KL Kiick, AM Kloxin, “Design of thiol- and light-sensitive degradable hydrogels using Michael-type addition reactions,” Polymer Chemistry, 6, 5565-5574, 2015. DOI:10.1039/C5PY00750J
- KA Tran, MY Cheng, A Mitra, H Ogawa, VY Shi, LP Olney, AM Kloxin, E Maverakis, “MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy,” Drug Design, Development and Therapy, 10, 43-52, 2015. DOI: 10.2147/DDDT.S93545
- E Maverakis, LA Cornelius, GM Bowen, T Phan, FB Patel, S Fitzmaurice, Y He, B Burrall, C Duong, AM Kloxin, H Sultani, R Wilken, SR Martinez, F Patel, “Metastatic Melanoma – A Review of Current and Future Treatment Options,” Acta Dermato-Venereologica, 95, 516-527, 2015. DOI: 10.2340/00015555-2035
- LA Sawicki, AM Kloxin, “Design of thiol–ene photoclick hydrogels using facile techniques for cell culture applications,” Biomaterials Science, 2, 1612-1626, 2014. DOI: 10.1039/c4bm00187g
- PM Kharkar, AM Kloxin, KL Kiick, “Dually degradable click hydrogels for controlled degradation and protein release,” Journal of Materials Chemistry B, 2, 5511-5521, 2014. DOI: 10.1039/C4TB00496E
- ME Smithmyer, LA Sawicki, AM Kloxin, “Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease,” Biomaterials Science, 2, 634-650, 2014. DOI: 10.1039/C3BM60319A
- P Fischer [LeValley], M Tibbitt, A Kloxin, K Anseth, and J Oakey, “Photodegradable hydrogels for selective capture and release of mammalian cells,” Biomedical Sciences Instrumentation, 50, 62-67, 2014. http://www.ncbi.nlm.nih.gov/pubmed/25405405
- MS Rehmann, AC Garibian, AM Kloxin, “Degradable thiol−ene hydrogels for protein release,” Macromolecular Symposia, 329, 58-65, 2013. DOI: 10.1002/masy.201200133
- PM Kharkar, KL Kiick, AM Kloxin,“Designing hydrogels for orthogonal control of degradable cell microenvironments,” Chemical Society Reviews, 42, 7335-7372, 2013. DOI: 10.1039/C3CS60040H
- MS Rehmann, AM Kloxin, “Tunable and dynamic soft materials for three-dimensional cell culture,” Soft Matter, 9, 6737-6746, 2013. DOI:10.1039/C3SM50217A
- DD McKinnon, AM Kloxin, KS Anseth, “Synthetic hydrogel platform for three-dimensional culture of embryonic stem cell-derived motor neurons,” Biomaterials Science, 1, 460-469, 2013. DOI: 10.1039/C3BM00166K
- MW Tibbitt, AM Kloxin, LA Sawicki, KS Anseth, “Mechanical properties and degradation of chain and step polymerized photodegradable hydrogels,” Macromolecules, 46, 2785-2792, 2013. DOI: 10.1021/ma302522x
- MW Tibbitt, AM Kloxin, KS Anseth, “Modeling controlled photodegradation in optically thick hydrogels,” Journal of Polymer Science Part A: Polymer Chemistry, 9, 1899-1911, 2013. DOI: 10.1002/pola.26574
- AM Kloxin, KJR Lewis, CA DeForest, G Seedorf, MW Tibbitt, V Balasubramaniam, and KS Anseth, “Responsive culture platform to examine the influence of microenvironmental geometry on cell function in 3D,” Integrative Biology, 4, 1540-1549, 2012. DOI: 10.1039/C2IB20212C
- H Wang, SM Haeger, AM Kloxin, LA Leinwand, KS Anseth, “Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus,” PLoS One, 7, e39969, 2012. DOI: 10.1371/journal.pone.0039969
- MW Tibbitt, BW Han, AM Kloxin, KS Anseth, “Synthesis and application of photodegradable microspheres for spatiotemporal control of protein delivery,” Journal of Biomedical Materials Research Part A, 100, 1647-1654, 2012. DOI: 10.1002/jbm.a.34107
- AM Kloxin, MW Tibbitt, and KS Anseth, “Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms,” Nature Protocols, 5, 1867-1887, 2010. DOI: 10.1038/nprot.2010.139
- MW Tibbitt, AM Kloxin, KU Dyamenahalli, and KS Anseth, “Controlled two-photon photoerosion of PEG hydrogels to study and manipulate subcellular interactions on soft materials,” Soft Matter, 6, 5100-5108, 2010. DOI: 10.1039/C0SM00174K
- AM Kloxin, CJ Kloxin, CN Bowman, and KS Anseth, “Mechanical properties of cellularly responsive hydrogels and their experimental determination,” Advanced Materials, 22, 3484-3494, 2010. DOI: 10.1002/adma.200904179
- AM Kloxin, MW Tibbitt, AM Kasko, JA Fairbairn, and KS Anseth, “Tunable hydrogels through controlled photodegradation for external manipulation of the cell microenvironment,” Advanced Materials, 22, 61-66, 2010. DOI: 10.1002/adma.200900917
- AM Kloxin, JA Benton, and KS Anseth, “In situ elasticity modulation with dynamic substrates to direct cell phenotype,” Biomaterials, 33, 1-8, 2010. DOI: 10.1016/j.biomaterials.2009.09.025
- AM Kloxin, AM Kasko, CN Salinas, and KS Anseth, “Photolabile hydrogels for dynamic tuning of physical and chemical properties,” Science, 324, 59-63, 2009. DOI: 10.1126/science.1169494
- VS Khire, AM Kloxin, CC Clouch, KS Anseth, and CN Bowman, “Synthesis, characterization and cleavage of linear polymers attached to silica nanoparticles formed using thiol-acrylate conjugate addition reactions,” Journal of Polymer Science A: Polymer Chemistry, 46, 6896-6906, 2008. DOI: 10.1002/pola.22999
- CR Nuttelman, AM Kloxin, and KS Anseth, “Temporal changes in PEG hydrogel structure influence human mesenchymal stem cell proliferation and matrix mineralization,” Advances in Experimental Medicine and Biology: Tissue Engineering, 585, 135-149, 2006. DOI: 10.1007/978-0-387-34133-0_10
Patents and patent applications
- “Light triggered wound mimicking system,” Patent Application US63/595,790, filed November 03, 2023.
- AM Kloxin, L Pradhan, R Sikes K van Golen, D Moore, “Indirect three-dimensional co-culture of dormant tumor cells and uses thereof,” Patent Application US17/764,593, US20220356452A1, filed September 30, 2020.
- KL Kiick, AM Kloxin, PM Kharkar, R Sivamani, E Maverakis, “Multimode degradable hydrogels for controlled release of cargo substances,” Patent US15/307,701, US20170258907A1, granted January 8, 2019.
- MW Tibbitt, KS Anseth, AM Kloxin, M Toner, J Oakey, A Shah, “Selective capture and release of rare cells using photodegradable hydrogels in a microfluidic platform,” Patent Application US14/905,460, US20160153999A1, granted March 1, 2022.
- KS Anseth, AM Kasko, MW Tibbitt, AM Kloxin, B Sridhar, “Photodegradable groups for tunable polymeric materials,” Patent US13/725,674, US9180196B2, granted November 10, 2015.