Chromo-fluorogenic probes for beta-galactosidase detection

[EN] beta-Galactosidase (beta-Gal) is a widely used enzyme as a reporter gene in the field of molecular biology which hydrolyzes the beta-galactosides into monosaccharides. beta-Gal is an essential enzyme in humans and its deficiency or its overexpression results in several rare diseases. Cellular senescence is probably one of the most relevant physiological disorders that involve beta-Gal enzyme. In this review, we assess the progress made to date in the design of molecular-based probes for the detection of beta-Gal both in vitro and in vivo. Most of the reported molecular probes for the detection of beta-Gal consist of a galactopyranoside residue attached to a signalling unit through glycosidic bonds. The beta-Gal-induced hydrolysis of the glycosidic bonds released the signalling unit with remarkable changes in color and/or emission. Additional examples based on other approaches are also described. The wide applicability of these probes for the rapid and in situ detection of de-regulation beta-Gal-related diseases has boosted the research in this fertile fieldR.M laboratory members received the financial support from the Spanish Government (project RTI2018-100910-B-C41) and the Generalitat Valenciana (project PROMETEO 2018/024). B.L-T. received support from the Spanish Ministry of Economy for their PhD grants (FPU15/02707). J. F.-B received fellowship (CD19/00038)Lozano-Torres, B.; Blandez, JF.; Sancenón Galarza, F.; Martínez-Máñez, R. (2021). Chromo-fluorogenic probes for beta-galactosidase detection. Analytical and Bioanalytical Chemistry. 413(9):2361-2388. https://doi.org/10.1007/s00216-020-03111-8S236123884139Fernandes P. Enzymes in food processing: a condensed overview on strategies for better biocatalysts. Enzyme Res. 2010;2010:86253–73.Likidlilid A, Patchanans N, Peerapatdit T, Sriratanasathavorn C. 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Glycosyltransferase and glycosidase activities in ovarian cancer

Fluorogenic Detection of Human Serum Albumin Using Curcumin-Capped Mesoporous Silica Nanoparticles

[EN] Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v/v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.This research was funded by the Spanish Government (RTI2018-100910-B-C41 (MCUI/FEDER, EU)) and the Generalitat Valenciana (PROMETEO 2018/024). I.O. was funded by Erasmus Mundus Programme, Action 2, Lot 1, Syria (predoctoral fellowship). S.M. was funded by Generalitat Valenciana (Santiago Grisolia fellowship).Otri, I.; Medaglia, S.; Aznar, E.; Sancenón Galarza, F.; Martínez-Máñez, R. (2022). Fluorogenic Detection of Human Serum Albumin Using Curcumin-Capped Mesoporous Silica Nanoparticles. Molecules. 27(3):1-9. https://doi.org/10.3390/molecules270311331927

Mimicking tricks from nature with sensory organic-inorganic hybrid materials

Design strategies for (bio)chemical systems that are inspired by nature's accomplishments in system design and operation on various levels of complexity are increasingly gaining in importance. Within the broad field of biomimetic chemistry, this article highlights various attempts toward improved and sophisticated sensory materials that rely on the combination of supramolecular (bio)chemical recognition principles and nanoscopic solid structures. Examples range from more established concepts such as hybrid sensing ensembles with improved sensitivity and selectivity or for target analytes for which selectivity is hard to achieve by conventional methods, which were often inspired by protein binding pockets or ion channels in membranes, to very recent approaches relying on target-gated amplified signalling with functionalised mesoporous inorganic supports and the integration of native biological sensory species such as transmembrane proteins in spherically supported bilayer membranes. 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A Versatile New Paradigm for the Design of Optical Nanosensors Based on Enzyme-Mediated Detachment of Labeled Reporters: The Example of Urea Detection

"This is the peer reviewed version of the following article: Llopis-Lorente, Antoni, Reynaldo Villalonga, M. Dolores Marcos, Ramón Martínez-Máñez, and Félix Sancenón. 2018. A Versatile New Paradigm for the Design of Optical Nanosensors Based on Enzyme‐Mediated Detachment of Labeled Reporters: The Example of Urea Detection. Chemistry A European Journal 25 (14). Wiley: 3575 81. doi:10.1002/chem.201804706. , which has been published in final form at https://doi.org/10.1002/chem.201804706. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Here, a new bio-inspired nanoarchitectonics approach for the design of optical probes is presented. It is based on nanodevices that combine 1) an enzymatic receptor subunit, 2) a signaling subunit (consisting of a labeled reporter attached to a silica surface), and 3) a mechanism of communication between the two sites based on the production of chemical messengers by the enzymatic subunit, which induces the detachment of the reporter molecules from the silica surface. As a proof of concept, a urea nanosensor based on the release of Alexa-Fluor-647-labeled oligonucleotide from enzyme-functionalized Janus gold-mesoporous-silica nanoparticles (Au-MSNPs) was developed. The Janus particles were functionalized on the silica face with amino groups to which the labeled oligonucleotides were attached by electrostatic interactions, whereas the gold face was used for grafting urease enzymes. The nanodevice was able to release the fluorescent oligonucleotide through the enzyme-mediated hydrolysis of urea to ammonia and the subsequent deprotonation of amino groups on the silica face. This simple nanodevice was applied for the fluorometric detection of urea in real human blood samples and for the identification of adulterated milk. Given the large variety of enzymes and reporter species that could be combined, this is a general new paradigm that could be applied to the design of a number of optical probes for the detection of target analytes.A.L.-L. is grateful to "La Caixa" Banking Foundation for his Ph.D. fellowship. The authors thank to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, AGL2015-70235-C2-2-R, CTQ2014-58989-P and CTQ2015-71936-REDT) and the Generalitat Valencia (Projects PROMETEOII/2014/047, PROMETEO2018/024) for support. The Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) is also gratefully acknowledged.Llopis-Lorente, A.; Villalonga, R.; Marcos Martínez, MD.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). A Versatile New Paradigm for the Design of Optical Nanosensors Based on Enzyme-Mediated Detachment of Labeled Reporters: The Example of Urea Detection. Chemistry - A European Journal. 25(14):3575-3581. https://doi.org/10.1002/chem.201804706S35753581251

Colorimetric detection of normetanephrine, a pheochromocytoma biomarker, using bifunctionalised gold nanoparticles

[EN] A simple and effective colorimetric method for the detection of normetanephrine (NMN), an O-methylated metabolite of norepinephrine, using functionalised gold nanoparticles is described. This metabolite is an important biomarker in the diagnosis of adrenal tumours such as pheocromocytoma or paraganglioma. The colorimetric probe consists of spherical gold nanoparticles (AuNPs) functionalised with two different ligands, which specifically recognize different functional groups in normetanephrine. Thus, a benzaldehyde-terminated ligand was used for the recognition of the amino alcohol moiety in NMN, by forming the corresponding oxazolidine. On the other hand, N-acetyl-cysteine was chosen for the recognition of the phenolic hydroxyl group through the formation of hydrogen bonds. The selective double molecular recognition between the probe and the hydroxyl and the amino-alcohol moieties of normetanephrine led to interparticle-crosslinking aggregation resulting in a change in the color of the solution, from red to blue, which could be observed by naked eye. The probe was highly selective towards normetanephrine and no color changes were observed in the presence of other neurotransmitter metabolites such as homovanillic acid (HVA) (dopamine metabolite), 5-hydroxyindoleacetic acid (5-HIAA) (serotonin metabolite), or other biomolecules present in urine such as glucose (Glc), uric acid (U.A), and urea. Finally, the probe was evaluated in synthetic urine with constituents that mimic human urine, where a limit of detection of 0.5 mu M was achieved.Financial support from the Spanish Government (project MAT2015-64139-C4) and Generalitat Valenciana (Project PROMETEOII/2014/047 and AICO/2017/093) is gratefully acknowledged. T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisolia fellowship.Godoy-Reyes, TM.; Costero, AM.; Gaviña, P.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). Colorimetric detection of normetanephrine, a pheochromocytoma biomarker, using bifunctionalised gold nanoparticles. Analytica Chimica Acta. 1056:146-152. https://doi.org/10.1016/j.aca.2019.01.003S146152105

Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency

[EN] The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 +/- 8.1 nm). From the isotherm curve, a specific surface area of 872 m(2)/g was estimated along with a pore volume of 0.85 crn(3)/g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology. (C) 2018 Elsevier B.V. All rights reserved.The authors would like to thank the National Scientific and Technological Research Council (CNPQ) and the Rio de Janeiro State Research Foundation (FAPERJ) for funding. Authors also gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Project MAT2012-38429-004-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.Helal-Neto, E.; Sánchez-Cabezas, S.; Sancenón Galarza, F.; Martínez-Máñez, R.; Santos-Oliveira, R. (2018). Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency. Journal of Pharmaceutical and Biomedical Analysis. 153:90-94. https://doi.org/10.1016/j.jpba.2018.02.017S909415

A Colorimetric Probe for the Selective Detection of Norepinephrine Based on a Double Molecular Recognition with Functionalized Gold Nanoparticles

[EN] A simple colorimetric probe for the selective and sensitive detection of neurotransmitter norepinephrine (NE), an important biomarker in the detection of tumors such as pheochromocytoma and paraganglioma, is described. The sensing strategy is based on the use of spherical gold nanoparticles functionalized with benzaldehyde and boronic acid-terminated moieties. A double molecular recognition involving on one hand the aromatic aldehyde and the aminoalcohol group of NE, and on the other hand the boronic acid and the catechol moiety of the neurotransmitter, results in analyte triggered aggregation of the gold nanoparticles, leading to a bathochromic shift of the SPR band in the UV-vis spectrum of the probe and a clear change in the color of the solution from red to blue. Probe P1 shows a remarkable selectivity toward NE versus other catecholamine neurotransmitters (dopamine and epinephrine) and selected biomolecules (S-HIAA, L-Tyr, glucose, uric acid, Lys and glutamic acid). Moreover, a linear response to NE in the 0-1 mu M concentration range was observed and a limit of detection of 0.07 mu M in aqueous media was determined by UV-vis spectroscopy. The sensitivity of the probe toward NE in synthetic urine was also evaluated. In this medium, a limit of detection of 0.09 mu M was obtained which falls within the range of clinical interestFinancial support from the Spanish Government (Projects MAT2015-64139-C4-1-R and MAT2015-64139-C4-4-R) and the Generalitat Valencia (Projects PROMETEOII/2014/047 and AICO/2017/093) is gratefully acknowledged. T. Godoy-Reyes is grateful to the Generalitat Valenciana for her Santiago Grisolia fellowship.Godoy-Reyes, TM.; Costero, AM.; Gaviña, P.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). A Colorimetric Probe for the Selective Detection of Norepinephrine Based on a Double Molecular Recognition with Functionalized Gold Nanoparticles. ACS Applied Nano Materials. 2(3):1367-1373. https://doi.org/10.1021/acsanm.8b02254S136713732

Simple Endotoxin Detection Using Polymyxin-B-Gated Nanoparticles

"This is the peer reviewed version of the following article: Otri, Ismael, Sameh El-Sayed, Serena Medaglia, Ramón Martínez-Máñez, Elena Aznar, and Félix Sancenón. 2019. Simple Endotoxin Detection Using Polymyxin-B&-Gated Nanoparticles. Chemistry A European Journal 25 (15). Wiley: 3770 74. doi:10.1002/chem.201806306, which has been published in final form at https://doi.org/10.1002/chem.201806306. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] A nanodevice based on mesoporous silica nanoparticles with rhodamine B in the pore framework, functionalized with carboxylates on the outer surface and capped with the cationic polymyxin B peptide, was used to selectively detect endotoxin in aqueous solutions with a limit of detection in the picomolar range.The authors thank the Spanish Government (MAT2015 64139-C4-1-R) and the Generalitat Valenciana (PROMETEO2018/024) for their support. I.O. thanks to Erasmus Mundus Programme, Action 2, Lot 1, Syria, for his predoctoral fellowship. S.S. is grateful to Spanish Ministerio de Economia y Competitividad for his Juan de la Cierva contract (FJCI-2015-27201).Otri, I.; El Sayed, S.; Medaglia, S.; Martínez-Máñez, R.; Aznar, E.; Sancenón Galarza, F. (2019). Simple Endotoxin Detection Using Polymyxin-B-Gated Nanoparticles. Chemistry - A European Journal. 25(15):3770-3774. https://doi.org/10.1002/chem.201806306S377037742515Ulevitch, R. J., & Tobias, P. S. (1994). Recognition of endotoxin by cells leading to transmembrane signaling. Current Opinion in Immunology, 6(1), 125-130. doi:10.1016/0952-7915(94)90043-4YOUNG, L. S. (1977). Gram-Negative Rod Bacteremia: Microbiologic, Immunologic, and Therapeutic Considerations. Annals of Internal Medicine, 86(4), 456. doi:10.7326/0003-4819-86-4-456Mueller, M., Lindner, B., Kusumoto, S., Fukase, K., Schromm, A. B., & Seydel, U. (2004). Aggregates Are the Biologically Active Units of Endotoxin. Journal of Biological Chemistry, 279(25), 26307-26313. doi:10.1074/jbc.m401231200Bhattacharyya, J., Biswas, S., & Datta, A. (2004). Mode of Action of Endotoxin: Role of Free Radicals and Antioxidants. Current Medicinal Chemistry, 11(3), 359-368. doi:10.2174/0929867043456098Braun-Fahrländer, C., Riedler, J., Herz, U., Eder, W., Waser, M., Grize, L., … von Mutius, E. (2002). Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children. New England Journal of Medicine, 347(12), 869-877. doi:10.1056/nejmoa020057M. T. Madigan J. M. Martinko J. Parker T. D. Brock Brock Biology of Microorganisms 2000 Prentice Hall Upper Saddle River 793 794Reynolds, S. J., Milton, D. K., Heederik, D., Thorne, P. S., Donham, K. J., Croteau, E. A., … Larsson, L. (2005). Interlaboratory evaluation of endotoxin analyses in agricultural dusts—comparison of LAL assay and mass spectrometry. Journal of Environmental Monitoring, 7(12), 1371. doi:10.1039/b509256fPeters, M. (2006). Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness. Thorax, 61(2), 134-139. doi:10.1136/thx.2005.049403Peters, M., Fritz, P., & Bufe, A. (2012). A bioassay for determination of lipopolysaccharide in environmental samples. Innate Immunity, 18(5), 694-699. doi:10.1177/1753425912436590Lourenco, F. R., Botelho, T. D. S., & Pinto, T. D. J. A. (2012). How pH, Temperature, and Time of Incubation Affect False-Positive Responses and Uncertainty of the LAL Gel-Clot Test. PDA Journal of Pharmaceutical Science and Technology, 66(6), 542-546. doi:10.5731/pdajpst.2012.00887Voss, S., Fischer, R., Jung, G., Wiesmüller, K.-H., & Brock, R. (2007). A Fluorescence-Based Synthetic LPS Sensor. Journal of the American Chemical Society, 129(3), 554-561. doi:10.1021/ja065016pWu, J., Zawistowski, A., Ehrmann, M., Yi, T., & Schmuck, C. (2011). Peptide Functionalized Polydiacetylene Liposomes Act as a Fluorescent Turn-On Sensor for Bacterial Lipopolysaccharide. Journal of the American Chemical Society, 133(25), 9720-9723. doi:10.1021/ja204013uZeng, L., Wu, J., Dai, Q., Liu, W., Wang, P., & Lee, C.-S. (2010). Sensing of Bacterial Endotoxin in Aqueous Solution by Supramolecular Assembly of Pyrene Derivative. Organic Letters, 12(18), 4014-4017. doi:10.1021/ol1016228Lan, M., Wu, J., Liu, W., Zhang, W., Ge, J., Zhang, H., … Wang, P. (2012). Copolythiophene-Derived Colorimetric and Fluorometric Sensor for Visually Supersensitive Determination of Lipopolysaccharide. Journal of the American Chemical Society, 134(15), 6685-6694. doi:10.1021/ja211570aDullah, E. C., & Ongkudon, C. M. (2016). Current trends in endotoxin detection and analysis of endotoxin–protein interactions. Critical Reviews in Biotechnology, 37(2), 251-261. doi:10.3109/07388551.2016.1141393Prasad, P., Sachan, S., Suman, S., Swayambhu, G., & Gupta, S. (2018). Regenerative Core–Shell Nanoparticles for Simultaneous Removal and Detection of Endotoxins. Langmuir, 34(25), 7396-7403. doi:10.1021/acs.langmuir.8b00978Jurado-Sánchez, B., Pacheco, M., Rojo, J., & Escarpa, A. (2017). Magnetocatalytic Graphene Quantum Dots Janus Micromotors for Bacterial Endotoxin Detection. Angewandte Chemie International Edition, 56(24), 6957-6961. doi:10.1002/anie.201701396Jurado-Sánchez, B., Pacheco, M., Rojo, J., & Escarpa, A. (2017). Magnetocatalytic Graphene Quantum Dots Janus Micromotors for Bacterial Endotoxin Detection. Angewandte Chemie, 129(24), 7061-7065. doi:10.1002/ange.201701396Ahn, G., Sekhon, S. S., Jeon, Y.-E., Kim, M.-S., Won, K., Kim, Y.-H., & Ahn, J.-Y. (2017). Detection of endotoxins using nanomaterials. Toxicology and Environmental Health Sciences, 9(5), 259-268. doi:10.1007/s13530-017-0330-4Sancenón, F., Pascual, L., Oroval, M., Aznar, E., & Martínez-Máñez, R. (2015). Gated Silica Mesoporous Materials in Sensing Applications. ChemistryOpen, 4(4), 418-437. doi:10.1002/open.201500053Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456El Sayed, S., Giménez, C., Aznar, E., Martínez-Máñez, R., Sancenón, F., & Licchelli, M. (2015). Highly selective and sensitive detection of glutathione using mesoporous silica nanoparticles capped with disulfide-containing oligo(ethylene glycol) chains. Organic & Biomolecular Chemistry, 13(4), 1017-1021. doi:10.1039/c4ob02083aRibes, À., Santiago-Felipe, S., Aviñó, A., Candela-Noguera, V., Eritja, R., Sancenón, F., … Aznar, E. (2018). Design of oligonucleotide-capped mesoporous silica nanoparticles for the detection of miRNA-145 by duplex and triplex formation. Sensors and Actuators B: Chemical, 277, 598-603. doi:10.1016/j.snb.2018.09.026Ribes, À., Xifré -Pérez, E., Aznar, E., Sancenón, F., Pardo, T., Marsal, L. F., & Martínez-Máñez, R. (2016). Molecular gated nanoporous anodic alumina for the detection of cocaine. Scientific Reports, 6(1). doi:10.1038/srep38649Mondragón, L., Mas, N., Ferragud, V., de la Torre, C., Agostini, A., Martínez-Máñez, R., … Orzáez, M. (2014). Enzyme-Responsive Intracellular-Controlled Release Using Silica Mesoporous Nanoparticles Capped with ε-Poly-L-lysine. Chemistry - A European Journal, 20(18), 5271-5281. doi:10.1002/chem.201400148Wang, Y., Zhang, D., Liu, W., Zhang, X., Yu, S., Liu, T., … Wang, J. (2014). Facile colorimetric method for simple and rapid detection of endotoxin based on counterion-mediated gold nanorods aggregation. Biosensors and Bioelectronics, 55, 242-248. doi:10.1016/j.bios.2013.12.006Su, W., Cho, M., Nam, J.-D., Choe, W.-S., & Lee, Y. (2013). Aptamer-Assisted Gold Nanoparticles/PEDOT Platform for Ultrasensitive Detection of LPS. Electroanalysis, 25(2), 380-386. doi:10.1002/elan.20120045

Mesoporous silica materials for controlled delivery based on enzymes

[EN] This review summarises examples of capped mesoporous silica materials for controlled delivery that use enzymes as external triggers or functional components of the gating ensemble.Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. A. Llopis-Lorente is grateful to "La Caixa'' Banking Foundation for his PhD fellowship. B. Lozano-Torres is grateful to the Spanish Ministry of Economy and Competitiveness (MEC) for her FPU grant. Also A. Bernardos thanks the Spanish MEC for her Juan de la Cierva Contract.Llopis-Lorente, A.; Lozano-Torres, B.; Bernardos Bau, A.; Martínez-Máñez, R.; Sancenón Galarza, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B. 5(17):3069-3083. https://doi.org/10.1039/C7TB00348JS3069308351

Synthesis of a new tripodal chemosensor based on 2,4,6-triethyl-1,3,5-trimethylbencene scaffolding bearing thiourea and fluorescein for the chromo-fluorogenic detection of anions

A tripodal receptor containing thiourea as binding site and fluorescein as signalling subunit has been designed, synthesized and used for the colorimetric detection of basic anions in DMSO solutions. (C) 2012 Elsevier Ltd. All rights reserved.Moragues Pons, ME.; Santos Figueroa, LE.; Abalos Aguado, T.; Sancenón Galarza, F.; Martínez Mañez, R. (2012). Synthesis of a new tripodal chemosensor based on 2,4,6-triethyl-1,3,5-trimethylbencene scaffolding bearing thiourea and fluorescein for the chromo-fluorogenic detection of anions. Tetrahedron Letters. 53(38):5110-5113. doi:10.1016/j.tetlet.2012.07.039S51105113533