Sociological and Communication-Theoretical Perspectives on the Commercialization of the Sciences

Both self-organization and organization are important for the further development of the sciences: the two dynamics condition and enable each other. Commercial and public considerations can interact and "interpenetrate" in historical organization; different codes of communication are then "recombined." However, self-organization in the symbolically generalized codes of communication can be expected to operate at the global level. The Triple Helix model allows for both a neo-institutional appreciation in terms of historical networks of university-industry-government relations and a neo-evolutionary interpretation in terms of three functions: (i) novelty production, (i) wealth generation, and (iii) political control. Using this model, one can appreciate both subdynamics. The mutual information in three dimensions enables us to measure the trade-off between organization and self-organization as a possible synergy. The question of optimization between commercial and public interests in the different sciences can thus be made empirical.Comment: Science & Education (forthcoming

14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in Head and Neck cancer cells

<p>Abstract</p> <p>Background</p> <p>The five-year survival rates for head and neck squamous cell carcinoma (HNSCC) patients are less than 50%, and the prognosis has not improved, despite advancements in standard multi-modality therapies. Hence major emphasis is being laid on identification of novel molecular targets and development of multi-targeted therapies. 14-3-3 zeta, a multifunctional phospho-serine/phospho-threonine binding protein, is emerging as an effector of pro-survival signaling by binding to several proteins involved in apoptosis (Bad, FKHRL1 and ASK1) and may serve as an appropriate target for head and neck cancer therapy. Herein, we determined effect of guggulsterone (GS), a farnesoid X receptor antagonist, on 14-3-3 zeta associated molecular pathways for abrogation of apoptosis in head and neck cancer cells.</p> <p>Methods</p> <p>Head and neck cancer cells were treated with guggulsterone (GS). Effect of GS-treatment was evaluated using cell viability (MTT) assay and apoptosis was verified by annexin V, DNA fragmentation and M30 CytoDeath antibody assay. Mechanism of GS-induced apoptosis was determined by western blotting and co-IP assays using specific antibodies.</p> <p>Results</p> <p>Using in vitro models of head and neck cancer, we showed 14-3-3 zeta as a key player regulating apoptosis in GS treated SCC4 cells. Treatment with GS releases BAD from the inhibitory action of 14-3-3 zeta in proliferating HNSCC cells by activating protein phosphatase 2A (PP2A). These events initiate the intrinsic mitochondrial pathway of apoptosis, as revealed by increased levels of cytochrome c in cytoplasmic extracts of GS-treated SCC4 cells. In addition, GS treatment significantly reduced the expression of anti-apoptotic proteins, Bcl-2, xIAP, Mcl1, survivin, cyclin D1 and c-myc, thus committing cells to apoptosis. These events were followed by activation of caspase 9, caspase 8 and caspase 3 leading to cleavage of its downstream target, poly-ADP-ribose phosphate (PARP).</p> <p>Conclusion</p> <p>GS targets 14-3-3 zeta associated cellular pathways for reducing proliferation and inducing apoptosis in head and neck cancer cells, warranting its investigation for use in treatment of head and neck cancer.</p

A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues

Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant) in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons), and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness

Enzymatic Glucose Based Bio batteries: Bioenergy to Fuel Next Generation Devices

[EN] This article consists of a review of the main concepts and paradigms established in the field of biological fuel cells or biofuel cells. The aim is to provide an overview of the current panorama, basic concepts, and methodologies used in the field of enzymatic biofuel cells, as well as the applications of these bio-systems in flexible electronics and implantable or portable devices. Finally, the challenges needing to be addressed in the development of biofuel cells capable of supplying power to small size devices with applications in areas related to health and well-being or next-generation portable devices are analyzed. The aim of this study is to contribute to biofuel cell technology development; this is a multidisciplinary topic about which review articles related to different scientific areas, from Materials Science to technology applications, can be found. With this article, the authors intend to reach a wide readership in order to spread biofuel cell technology for different scientific profiles and boost new contributions and developments to overcome future challenges.Financial support from the Spanish Ministry of Science, Innovation and University, through the State Program for Talent and Employability Promotion 2013-2016 by means of Torres Quevedo research contract in the framework of Bio2 project (PTQ-14-07145) and from the Instituto Valenciano de Competitividad Empresarial-IVACE-GVA (BioSensCell project)Buaki-Sogo, M.; García-Carmona, L.; Gil Agustí, MT.; Zubizarreta Saenz De Zaitegui, L.; García Pellicer, M.; Quijano-Lopez, A. (2020). Enzymatic Glucose Based Bio batteries: Bioenergy to Fuel Next Generation Devices. Topics in Current Chemistry (Online). 378(6):1-28. https://doi.org/10.1007/s41061-020-00312-8S1283786Schlögl R (2015) The revolution continues: Energiewende 2.0. Angew Chem Int Ed 54:4436–4439Mitcheson PD, Yeatman EM, Rao GK, Holmes AS, Green TC (2008) Energy harvesting from human and machine motion for wireless electronic devices. Proc IEEE 96(9):1457–1486Wang ZL, Wu W (2012) Nanotechnology-enabled energy harvesting for self-powered micro-/nanosystems. Angew Chem Int Ed 51:11700-11721Lamy C, Lima A, LeRhun V, Delime F, Coutanceau C, Léger J-M (2002) Recent advances in the development of direct alcohol fuel cells (DAFC). J Power Sources 105:283Cheng X, Shi Z, Glass N, Zhang L, Zhang J, Song D, Liu Z-S, Wang H, Shen J (2007) A review of PEM hydrogen fuel cell contamination: impacts, mechanisms, and mitigation. J Power Sources 165:739Boudghere Stambouli A, Traversa E (2002) Solid oxide fuel cells (SOFC): a review of an environmentally clean and efficient source of energy. Renew Sustain Energy Rev 6:433–455Qiao Y, Li CM (2011) Nanostructured catalyst in fuel cells. J Mater Chem 21:4027–4036Edwards PP, Kuznetsov VL, David WIF, Brandon NP (2008) Hydrogen and fuel cells: towards sustainable energy future. Energy Policy 36:4356–4362Kirubakaran A, Jain S, Nema RK (2009) A review on fuel cell technologies and power electronic interface. Renew Sustain Energy 13:2430–2440Kerzenmacher S, Ducree J, Zengerle R, von Stetten F (2008) An abiotically catalyzed glucose fuel cell for powering medical implants: reconstructed manufacturing protocol and analysis of performance. J Power Sources 182:66–75Drake RF, Kusserow BK, Messinger S, Matsuda S (1970) A tissue implantable fuel cell power supply. Trans Am Soc Artif Intern Organs 16:199–205Giner J, Holleck G, Malachesky PA (1973) Eine implantierbare Brennstoffzelle zum Betrieb eines mechanischen Herzens. Phys Chem 77:782–783. https://doi.org/10.1002/bbpc.19730771009Cosnier S, LeGoff A, Holzinger M (2014) Towards glucose biofuel cells implanted in human body for powering artificial organs: review. Electrochem Commun 38:19–23Katz E (2015) Implantable biofuel cells operating in vivo—potential power sources for bioelectronic devices. Bioelectron Med 2:1–12Bullen RA, Arnot TC, Lakeman JB, Walsh FC (2006a) Biofuel cells and their development . Biosens Bioelectron 21:2015–2045Cooney MJ, Svoboda V, Lau C, Martin G, Minteer SD (2008) Enzyme catalysed biofuel cells. Energy Environ Sci 1:320–337Cracknell JA, Vincent KA, Armstrong FA (2008) Enzymes as working or inspirational electrocatalysts for fuel cells and electrolysis. Chem Rev 108:2439–2461Sheldon RA (2007) Enzyme immobilization: the quest for optimum performance. Adv Synth Catal 349:1289–1307Bullen RA, Arnot TC, Lakeman JB, Walsh FC (2006b) Biofuel cells and their development. Biosens Bioelectron 21:2015–2045Koch C, Popiel D, Harnisch F (2014) Functional redundancy of microbial anodes fed by domestic wastewater. ChemElectroChem 1:1923–1931Mano N, Mao F, Heller A (2003) Characteristics of a miniature compartment-less glucose−O2 biofuel cell and its operation in a living plant. J Am Chem Soc 125(21):6588–6594Mano N, Mao F, Heller A (2002) A miniature biofuel cell operating in a physiological buffer. J Am Chem Soc 124(44):12962–12963Bruen D, Delaney C, Florea L, Diamond D (2017) Glucose sensing for diabetes monitoring: recent developments. Sensors 17:1866Falk M, Blum Z, Shleev S (2012) Direct electron transfer based enzymatic fuel cells. Electrochim Acta 82:191–202White HB (1976) Coenzymes as fossils of an earlier metabolic state. J Mol Evol 7:101–104Broderick JB (2001) Coenzymes and cofactors. In: eLS. Wiley, Chichester. https://www.els.net. https://doi.org/10.1038/npg.els.0000631Sakurai T, Kataoka K (2007) Basic and applied features of multicopper oxidases, CueO, bilirubin oxidase, and laccase. Chem Rec 7:220–229Bankar SB, Bule MV, Singhal RS, Ananthanarayan L (2009) Glucose oxidase—an overview. Biotech Adv 27:489–501Ferri S, Kojima K, Sode K (2011) Review of glucose oxidases and glucose dehydrogenases: a bird’s eye view of glucose sensing enzymes. J Diabetes Sci Technol 5:1068–1076Katz E, MacVittie K (2013) Implanted biofuel cells operating in vivo—methods, applications and perspectives—feature article. Energy Environ Sci 6:2791–2803Ghindilis AL, Atanasov P, Wilkins E (1997) Enzyme catalysed direct electron transfer: fundamentals and analytical applications. Electroanalysis 9:661–674Von Woedtke Th, Fisher U, Abel P (1994) Glucose oxidase electrodes: effect of H2O2 on enzyme activity? Biosens Bioelectron 9:65–71Kleppe K (1966) The effect of H2O2 on glucose oxidase from Aspergillus niger. Biochemistry 5:139–143Zebda A, Godran C, Le Goff A, Holzinger M, Cinquin P, Cosnier S (2011) Mediatorless high-power glucose biofuel cells based on compressed carbon nanotube-enzyme electrodes. Nat Commun 2:370Borenstein A, Hanna O, Attias R, Luski S, Brousse T, Aurbach D (2017) Carbon-based composite materials for supercapacitor electrodes: a review. J Mater Chem A 5:12653–12672Angione MD, Pilolli R, Cotrone S, Magliulo M, Mallardi A, Palazzo G, Sabbatini L, Fine D, Dodabalapur A, Lioffi N, Torsi L (2011) Carbon based nanomaterials for electronic bio-sensing. Mat Today 14:424–433Cha C, Shin SR, Annabi N, Dokmeci MR, Khademhosseini A (2013) Carbon based nanomaterials: multifunctional materials for biomedical engineering. ACS Nano 7:2891–2897Wang Z, Dai Z (2015) Carbon nanomaterials-based electrochemical biosensors: an overview. Nanoscale 7:6420–6431Jariwala D, Sangwan VK, Lauhon LJ, Marks TJ, Hersam MC (2013) Carbon nanomaterials for electronics, optoelectronics, photovoltaics and sensing. Chem Soc Rev 42:2824–2860Babadi AA, Bagheri S, Abdul Hamid SB (2016) Progress on implantable biofuel cell: nano-carbon functionalization for enzyme immobilization enhancement. Biosens Bioelectron 15:850–860Osadebe I, Leech D (2014) Effect of multi-walled carbon nanotubes on glucose oxidation by glucose oxidase or a flavin-dependent glucose dehydrogenase in redox-polymer-mediated enzymatic fuel cell anodes. ChemElectroChem 1:1988–1993Si P, Huang Y, Wang T, Ma J (2013) Nanomaterials for electrochemical non-enzymatic glucose biosensors. RSC Adv 3:3487–3502Putzbach W, Ronkainen NJ (2013) Immobilization techniques in the fabrication of nanomaterial-based electrochemical biosensors: a review. Sensors 13(4):4811–4840Walcarius A, Minteer SD, Wang J, Lin Y, Merkoçi A (2013) Nanomaterials for bio-functionalized electrodes: recent trends. J Mater Chem B 1:4878–4908Datta S, Christena LR, Rajaram YRS (2013) Enzyme immobilization: an overview on techniques and support materials. 3 Biotech 3(1):1–9Ivanov I, Vidaković-Koch T, Sundmaker K (2010) Recent advances in enzymatic fuel cells; experiments and modelling. Energies 3:803–846Nguyen HH, Kim M (2017) An overview of techniques in enzyme immobilization. Appl Sci Converg Technol 26(6):157–163Fu J, Reinhold J, Woodbury NW (2011) Peptide-modified surfaces for enzyme immobilization. PLoS One 6(4):e18692Lee DH, Park CH, Yeo JM, Kim SW (2006) Lipase immobilization on silica gel using a cross-linking method. J Ind Eng Chem 12(5):777–782Szymańska K, Bryjak J, Jarzębski AB (2009) Immobilization of invertase on mesoporous silicas to obtain hyper active biocatalysts. Top Catal 52:1030–1036Al-Lolage F, Meneghello M, Ma S, Ludwig R, Barlett PN (2017) A flexible method for the stable, covalent immobilization of enzymes at electrode surfaces. ChemElectroChem 4:1528–1534Gutierrez-Sanchez C, Shleev S, De Lacey AL, Pita M (2015) Third-generation oxygen amperometric biosensor based on Trametes hirsuta laccase covalently bound to graphite electrode. Chem Pap 69:237–240Pita M, Gutierrez-Sanchez C, Toscano MD, Shleev S, De Lacey AL (2013) Oxygen biosensor based on bilirubin oxidase immobilized on a nanostructured gold electrode. Bioelectrochemistry 94:69–74Vaz-Dominguez C, Campuzano S, Rüdiger O, Pita M, Gorbacheva M, Shleev S, Fernandez VM, de Lacey LA (2008) Laccase electrode for direct electrocatalytic reduction of O2 to H2O with high-operational stability and resistance to chloride inhibition. Biosens Bioelectron 24(4):531–537Gutiérrez-Sánchez C, Jia W, Beyl Y, Pita M, Schuhmann W, de Lacey LA, Stoica L (2012) Enhanced direct electron transfer between laccase and hierarchical carbon microfibers/carbon nanotubes composite electrodes. Comparison of three enzyme immobilization methods. Electrochim Acta 82:218–223Lv Y, Jin S, Wang Y, Lun Z, Xia C (2016) Recent advances in the application of nanomaterials in enzymatic glucose sensors. J Iran Chem Soc 13(10):1767–1776Zhao C, Gai P, Song R, Chen Y, Zhang J, Zhu J-J (2017) Nanostructured material-based biofuel cells: recent advances and future prospects. Chem Soc Rev 46:1545–1564Yu EH, Scott K (2010) Enzymatic biofuel cells—fabrication of enzyme electrodes. Energies 3:23–42Minteer SD, Atanassov P, Luckarift HR, Johnson GR (2013) New materials for biological fuel cells. Mater Today 15(4):166–173Sarma AK, Vatsyayan P, Goswami P, Minteer SD (2009) Recent advances in material science for developing enzyme electrodes. Biosens Bioelectron 24:2313–2322Jesionowski T, Zdarta J, Krajewska B (2014) Enzyme immobilization by adsorption: a review. Adsorption 20:801–821Sardar M, Gupta MN (2005) Immobilization of tomato pectinase on Con A-Seralose 4B by bioaffinity layering. Enzyme Microbial Technol 37:355–359Sheldon RA (2011) Characteristic features and biotechnological applications of cross-linked enzyme aggregates (CLEAs). Appl Microbiol Biotechnol 92:467–477Velasco-Lozano S, López-Gallego F, Mateos-Díaz JC, Favela-Torres E (2015) Cross-linked enzyme aggregates (CLEA) in enzyme improvement—a review. Biocatalysis 1:166–177Cosnier S (1999) Biomolecule immobilization on electrode surfaces by entrapment or attachment to electrochemically polymerized films. A review. Biosen Bioelectron 14:443–456Heller A (1990) Electrical wiring of redox enzymes. Acc Chem Res 29:128–134Heller A (1992) Electrical connection of enzyme redox centres to electrodes. J Phys Chem 96:3579–3587Martins MVA, Pereira AR, Luz RAS, Iost RM, Crespilho FN (2014) Evidence of short-range electron transfer of a redox enzyme on graphene oxide electrodes. Phys Chem Chem Phys 16:17426–17436Luz RAS, Pereira AR, de Souza JCP, Sales FCPF, Crespilho FN (2014) Enzyme biofuel cells: thermodynamics. Kinetics and challenges in applicability. ChemElectroChem 1(11):1751–1777Neto SA, De Andrade AR (2013) New energy sources: the enzymatic biofuel cell. J Braz Chem Soc 24(12):1891–1912Rapoport BI, Kedzierski JT, Sarpeshkar R (2012) A glucose fuel cell for implantable brain–machine interfaces. PLoS One 7(6):6 e38436Zebda A, Alcaraz J-P, Vadgama P, Shleev S, Minteer SD, Boucher F, Cinquin P, Martin DK (2018) Challenges for successful implantation of biofuel cells. Bioelectrochemistry 124:57–72Ferraris RP, Diamond J (1997) Regulation of intestinal sugar transport. Physiol Rev 77:257–301Sprague JE, Arbeláez AM (2011) Glucose counterregulatory responses to hypoglicemia. Pediatr Endocrinol Rev 9:463–475Slaughter G, Kulkarni T (2019) Detection of human plasma glucose using a self-powered glucose biosensor. Energies 12:825Rathee K, Dhull V, Dhull R, Singh S (2016) Biosensors based on electrochemical lactate detection: a comprehensive review. Biochem Biophys Rep 5:35–54Koushanpour A, Gamella M, Katz E (2017) A biofuel cell based on biocatalytic reactions of lactate on both anode and cathode electrodes—extracting electrical power from human sweat. Electroanalysis 29:1602–1611Yao Y, Li H, Wang D, Liu C, Zhang C (2017) An electrochemiluminescence cloth-based biosensor with smartphone-based imaging for detection of lactate in saliva. Analyst 142:3715–3724Pankratov D, González-Arribas E, Blum Z, Shleev S (2016) Tear based bioelectronics. Electroanalysis 28:1250–1266Krogstad AL, Jansson PA, Gisslen P, Lönnroth P (1996) Microdialysis methodology for the measurement of dermal interstitial fluid in humans. Br J Dermatol 134(6):1005–1012Bandodkar AJ, Wang J (2016) Wearable biofuel cells: a review. Electroanalysis 28:1188–1200Jia W, Valdés-Ramírez G, Bandodkar AJ, Windmiller JR, Wang J (2013) Epidermal biofuel cells: energy harvesting from human perspiration. Angew Chem Int Ed 52:1–5Jeerapan I, Sempionatto JR, Pavinatto A, You J-M, Wang J (2016) Stretchable biofuel cells as wearable textile-based self-powered sensors. J Mater Chem A 4:18342–18353Valdés-Ramírez G, Li Y-G, Kima J, Jia W, Bandodkar AJ, Nuñez-Flores R, Miller PR, Wu S-Y, Narayan R, Windmiller JR, Polsky R, Wang J (2016) Microneedle-based self-powered glucose sensor. Electrochem Commun 47:58–62Gamella M, Koushanpour A, Katz E (2018) Biofuel cells—activation of micro- and macro- electronic devices. Bioelectrochemistry 119:33–42Mano N, Mao F, Shin W, Chen T, Heller A (2003) A miniature biofuel cell operating at 0.78 V. Chem Commun 20:518–519Shi B, Li Z, Fan Y (2018) Implantable energy harvesting devices. Adv Mater 30:1801511MacVittie K, Halámek J, Halámková L, Southcott M, Jemison WD, Lobel R, Katz E (2013) From “cyborg” lobsters to a pacemaker powered by implantable biofuel cells. Energy Environ Sci 6:81–86Szczupak A, Halámek J, Halámková L, Bocharova V, Alfonta L, Katz E (2012) Living battery—biofuel cells operating in vivo in clams. Energy Environ Sci 5:8891–8895Southcott M, MacVittie K, Halámek J, Halámková L, Jemison WD, Lobel R, Katz E (2013) A pacemaker powered by an implantable biofuel cell operating under conditions mimicking the human blood circulatory system—battery not included. Phys Chem Chem Phys 15:6278–6283MacVittie K, Conlon T, Katz E (2015) A wireless transmission system powered by an enzyme biofuel cell implanted in an orange. Bioelectrochemistry 106:28–33Aghahosseini H, Ramazani A, Asiabi PA, Gouranlou F, Hosseini F, Rezaei A, Min B-K, Joo SW (2016) Glucose-based biofuel cells: nanotechnology as a vital science in biofuel cell performance. Nanochem Res 1(2):83–204Zebda A, Cosnier S, Alcaraz J-P, Holzinger M, Le Goff A, Gondran C, Boucher F, Giroud F, Gorgy K, Lamraoui H, Cinquin P (2013) Single glucose biofuel cells implanted in rats power electronic devices. Sci Rep 2013:1516Ichi-Ribault SE, Alcaraz J-P, Boucher F, Boutaud B, Dalmolin R, Boutonnat J, Cinquin P, Zebda A, Martin DK (2018) Remote wireless control of an enzymatic biofuel cell implanted in a rabbit for 2 months. Electrochim Acta 269:360–366Bandodkar A (2017) Review—wearable biofuel cells: past, present and future. J Electrochem Soc 164(3):H3007–H3014Coman V, Ludwig R, Harreither W, Haltrich D, Gorton L, Ruzgas T, Shleev S (2010) A direct electron transfer-based glucose/oxygen biofuel cell operating in human serum. Fuel Cells 10(1):9–16Shoji K, Akiyama Y, Suzuki M, Nakamura N, Ohno H, Morishima K (2016) Biofuel cell backpacked insect and its application to wireless sensing. Biosens Bioelectron 78:390–395Reuillard B, Abreu C, Lalaoui N, Le Goff A, Holzinger M, Ondel O, Buret F, Cosnier S (2015) One-year stability for a glucose/oxygen biofuel cell combined with pH reactivation of the laccase/carbon nanotube biocathode. Bioelectrochemistry 106:73–76Sales FCPF, Iost RM, Martins MVA, Almeida MC, Crespilho FN (2013) An intravenous implantable glucose/dioxygen biofuel cell with modified flexible carbon fiber electrodes. Lab Chip 13:468Falk M, Narvez Villarrubia CW, Babanova S, Atanassov P, Shleev S (2013) Biofuel cells for biomedical applications: colonizing the animal kingdom. ChemPhysChem 14:2045–2058Rasmussen M, Ritzmann RE, Lee I, Pollack AJ, Scherson D (2012) An implantable biofuel cell for a live insect. J Am Chem Soc 134(3):1458–1460Halámková L, Halámek J, Bocharova V, Szczupak A, Alfonta L, Katz E (2012) Implanted biofuel cell operating in a living snail. J Am Chem Soc 134:5040–5043Cinquin P, Gondran C, Giroud F, Mazabrard S, Pellisier A, Boucher F, Alcaraz J-P, Gorgy K, Lenouvel F, Mathé S, Porcu P, Cosnier S (2010) A glucose biofuel cell implanted in rats. Plos One 5(5):e010476Chen C, Xie Q, Yang D, Xiao H, Fu Y, Tan S, Yao S (2013) Recent advances in electrochemical glucose biosensors: a review. RSC Adv 3:4473–4491Andoralov V, Falk M, Suyatin DB, Granmo M, Sotres J, Ludwig R, Popov VO, Schouenborg J, Blum Z, Shleev S (2013) Biofuel cell based on microscale nanostructured electrodes with inductive coupling to rat brain neuronsVerbeek MM, Leen WG, Willemsen MA, Slats D, Claassen JA (2016) Hourly analysis of cerebrospinal fluid glucose shows large diurnal fluctuations. J Cereb Blood F Met 36(5):899–902González-Guerrero MJ, Del Campo FJ, Esquivel JP, Leech D, Sabaté N (2017) Paper-based microfluidic biofuel cell operating under glucose concentrations within physiological range. Biosens Bioelectron 90:475–480Takeuchi ES, Leising RA (2002) Lithium batteries for biomedical applications. MRS Bull 27(8):624–627Bock DC, Marschilok A, Takeuchi KJ, Takeuchi ES (2012) Batteries used to power implantable biomedical devices. Electrochim Acta 84:155–164Greatbatch W, Lee JH, Mathias W, Eldridge M, Moser JR, Schneider AA (1971) The solid-state lithium battery: a new improved chemical power source for implantable cardiac pacemaker. IEEE Trans Biomed Eng 18(5):317–324Liu Y, Dong S (2007) A biofuel cell with enhanced power output by grape juice. Electrochem Commun 9(7):1423–1427Choi S, Lee H, Ghaffari R, Hyeon T, Kim D-H (2016) Recent advances in flexible and stretchable bio-electronic devices integrated with nanomaterials. Adv Mater 28:4203–4218Zhou L, Mao J, Ren Y, Han ST, Roy VAL, Zhou Y (2018) Recent advances of flexible data storage devices based on organic nanoscale materials. Small 14(10):1703126Gwon H, Kim H-S, Lee KU, Seo D-H, Park YC, Lee Y-S, Ahn BT, Kong K (2011) Flexible energy storage devices based on graphene paper. Energy Environ Sci 4:1277–1283Pang C, Lee C, Suh K-Y (2013) Recent advances in flexible sensors for wearable and implantable devices. J Appl Pol Sci 130:1429–1441Bandodkar AJ, Wang J (2014) Non-invasive wearable electrochemical sensors: a review. Trends Biotech 32(7):363–371Bandodkar AJ, Uia W, Wang J (2015) Tatto-based wearable electrochemical devices: a review. Electroanalysis 27(3):562–572Reid RC, Minteer SD, Gale BK (2015) Contact lens biofuel cell tested in a synthetic tear solution. Biosens Bioelectron 68:142Falk M, Andoralov V, Blum Z, Sotres J, Suyatin DM, Ruzgas T, Arnebrant T, Shleev S (2012) Biofuel cells as a power source for electronic contact lenses. Biosens Bioelectron 37(1):38–45Falk M, Andoralov V, Silow M, Toscano MD, Shleev S (2013) Miniature biofuel cell as a potential power source for Glucose-sensing contact lenses. Anal Chem 85(13):6342–6348Reid R, Jones SR, Hickey DP, Minteer SD, Gale BK (2016) Modeling carbon nanotubes connectivity and surface activity in a contact lens biofuel cell. Electrochim Acta 203:30–40Blum Z, Pankratov D, Shleev S (2014) Powering electronic contact lenses: current achievements, challenges and perspective. Expert Rev Ophthalmol 9(4):269–273Xiao X, Siepenkoetter T, Conghaile PÓ, Leech D, Magner E (2018) Nanoporous gold-based biofuel cell on contact lenses. ACS Appl Mater Interfaces 10(8):7107–7116Yang X-Y, Tian G, Jiang N, Su B-L (2012) Immobilization technology: a sustainable solution for biofuel cell design. Ener Environ Sci 5:5540–5563Mano N (2019) Engineering glucose oxidase for bioelectrochemical applications. Bioelectrochemistry 128:218–240Mate DM, Gonzalez-Perez D, Falk M, Kittl R, Pita M, De Lacey LA, Ludwig R, Shleev S, Alcalde M (2013) Blood tolerant caccase by directed evolution. Chem Biol 20:223–231Zhang L, Carucci C, Reculusa S, Goudeau B, Lefrançois P, Gounel S, Mano N, Kuhn A (2019) Rational design of enzyme-modified electrodes for optimized bioelectrocatalytic activity. ChemElectroChem 6(19):4980–4984Arechederra MN, Addo PK, Minteer SD (2011) Poly(neutral red) as a NAD+ reduction catalyst and a NADH oxidation catalyst: towards the development of a rechargeable biobattery. Electrochim Acta 56:1585Yang Y, Wang ZL (2015) Hybrid energy cells for simultaneously harvesting multi-types of energies. NanoEnergy 14:245–256Hansen BJ, Liu Y, Yang R, Wang ZL (2010) Hybrid nanogenerator for concurrently harvesting biomechanical and biochemical energy. ACS Nano 4:3647Song K, Han JH,

Learning to represent exact numbers

This article focuses on how young children acquire concepts for exact, cardinal numbers (e.g., three, seven, two hundred, etc.). I believe that exact numbers are a conceptual structure that was invented by people, and that most children acquire gradually, over a period of months or years during early childhood. This article reviews studies that explore children’s number knowledge at various points during this acquisition process. Most of these studies were done in my own lab, and assume the theoretical framework proposed by Carey (2009). In this framework, the counting list (‘one,’ ‘two,’ ‘three,’ etc.) and the counting routine (i.e., reciting the list and pointing to objects, one at a time) form a placeholder structure. Over time, the placeholder structure is gradually filled in with meaning to become a conceptual structure that allows the child to represent exact numbers (e.g., There are 24 children in my class, so I need to bring 24 cupcakes for the party.) A number system is a socially shared, structured set of symbols that pose a learning challenge for children. But once children have acquired a number system, it allows them to represent information (i.e., large, exact cardinal values) that they had no way of representing before

Shaping and Structuring Supramolecular Gels

Supramolecular gels assemble via non-covalent interactions between low-molecular-weight gelators (LMWGs). The gels form a solid-like nanoscale network spanning a liquid-like continuous phase, translating molecular-scale information into materials performance. However, gels based on LMWGs are often difficult to manipulate, easily destroyed and have poor rheological performance. The recurring image of newly-discovered supramolecular gels is that of an inverted vial showing that the gel can support its own weight against gravity. Such images reflect the limitation that these gels simply fill the vessel in which they are made, with limited ability to be shaped. This property prevents supramolecular gels from having the same impact as polymer gels, despite greater synthetic tunability, reversibility and bio/environmental compatibility. In this Review, we evaluate strategies for imposing different shapes onto supramolecular gels and for patterning structures within them. We review fabrication methods including moulding, self-healing, 3D printing, photopatterning, diffusion and surface-mediated patterning. We discuss gelator chemistries amenable to each method, highlighting how a multi-component approach can aid shaping and structuring. Supramolecular gels with defined shapes, or patterned structures with precisely-controlled compositions, have the potential to intervene in applications such as tissue engineering and nanoscale electronics, as well as opening-up new technologies

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1 diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1 diagnosis of the recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm. An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to have recurrence after the primary tumour resection. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Several clinicopathological parameters can be employed to assess outcome, recurrence and overall survival. © 2010 Jerjes et al; licensee BioMed Central Ltd