19 research outputs found

    Texture Analysis with Arbitrarily Oriented Morphological Opening and Closing

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    13 pagesThis paper presents a fast, streaming algorithm for 1-D morphological opening on 2-D support. The algorithm is further extended to compute the complete size distribution during a single image run. The Structuring Element (SE) can be oriented under arbitrary angle that allows us to perform different orientation-involved image analysis, such as local angle extraction, directional granulometries, \etc The algorithm processes an image in constant time irrespective of the SE orientation and size, with a minimal latency and very low memory requirements. Regardless the SE orientation, it reads and writes data strictly sequentially in the horizontal scan order. Aforementioned properties allow an efficient implementation in embedded hardware platforms that opens a new opportunity of a parallel computation, and consequently, a significant speed-up

    Stream implementation of serial morphological filters with approximated polygons

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    ISBN : 978-142448157-6International audienceThis paper describes an original stream implementation of serially composed morphological filters using approximated flat polygons. It strictly respects a sequential data access. Results are obtained with minimal latency while operating within minimal memory space; even for very large neighborhoods. This is interesting for serially composed advanced filters, such as Alternating Sequential Filters or granulometries. We show how the dedicated implementation on an FPGA allows obtaining a previously unequaled performance, opening an opportunity to use these operators in time-critical, high-end applications

    Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

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    The authors describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. The authors' results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.We thank the Spanish Government (projects SAF2010-21195 and MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. A.U. and C.G. are grateful to the Ministry of Education, Culture and Sport for their doctoral fellowships. We thank J. M. Cosgaya and M. J. Latasa for helpful discussions.Ultimo, A.; Giménez Morales, C.; Bartovsky, P.; Aznar, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2016). Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry - A European Journal. 22(5):1582-1586. https://doi.org/10.1002/chem.201504629S15821586225Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65(2), 87-108. doi:10.3322/caac.21262McGuire, A., Brown, J., Malone, C., McLaughlin, R., & Kerin, M. (2015). Effects of Age on the Detection and Management of Breast Cancer. Cancers, 7(2), 908-929. doi:10.3390/cancers7020815Stier, S., Maletzki, C., Klier, U., & Linnebacher, M. (2013). Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy. Clinical and Developmental Immunology, 2013, 1-14. doi:10.1155/2013/271246Huang, B., Zhao, J., Li, H., He, K.-L., Chen, Y., Mayer, L., … Xiong, H. (2005). Toll-Like Receptors on Tumor Cells Facilitate Evasion of Immune Surveillance. Cancer Research, 65(12), 5009-5014. doi:10.1158/0008-5472.can-05-0784Salaun, B., Coste, I., Rissoan, M.-C., Lebecque, S. J., & Renno, T. (2006). TLR3 Can Directly Trigger Apoptosis in Human Cancer Cells. The Journal of Immunology, 176(8), 4894-4901. doi:10.4049/jimmunol.176.8.4894Salaun, B., Zitvogel, L., Asselin-Paturel, C., Morel, Y., Chemin, K., Dubois, C., … Andre, F. (2011). TLR3 as a Biomarker for the Therapeutic Efficacy of Double-stranded RNA in Breast Cancer. Cancer Research, 71(5), 1607-1614. doi:10.1158/0008-5472.can-10-3490Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 122(40), 7439-7441. doi:10.1002/ange.201001847Lai, C.-Y., Trewyn, B. G., Jeftinija, D. M., Jeftinija, K., Xu, S., Jeftinija, S., & Lin, V. S.-Y. (2003). A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society, 125(15), 4451-4459. doi:10.1021/ja028650lLiu, R., Liao, P., Liu, J., & Feng, P. (2011). Responsive Polymer-Coated Mesoporous Silica as a pH-Sensitive Nanocarrier for Controlled Release. Langmuir, 27(6), 3095-3099. doi:10.1021/la104973jPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Park, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie, 119(9), 1477-1479. doi:10.1002/ange.200603404Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 50(47), 11172-11175. doi:10.1002/anie.201102756Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 123(47), 11368-11371. doi:10.1002/ange.201102756Bringas, E., Köysüren, Ö., Quach, D. V., Mahmoudi, M., Aznar, E., Roehling, J. D., … Stroeve, P. (2012). Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications, 48(45), 5647. doi:10.1039/c2cc31563gFu, Q., Rao, G. V. R., Ista, L. K., Wu, Y., Andrzejewski, B. P., Sklar, L. A., … López, G. P. (2003). Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials. Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dCliment, E., Bernardos, A., Martínez-Máñez, R., Maquieira, A., Marcos, M. D., Pastor-Navarro, N., … Amorós, P. (2009). Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers. Journal of the American Chemical Society, 131(39), 14075-14080. doi:10.1021/ja904456dPark, C., Kim, H., Kim, S., & Kim, C. (2009). Enzyme Responsive Nanocontainers with Cyclodextrin Gatekeepers and Synergistic Effects in Release of Guests. Journal of the American Chemical Society, 131(46), 16614-16615. doi:10.1021/ja9061085Patel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 48(17), 3092-3095. doi:10.1002/anie.200805818Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie, 121(17), 3138-3141. doi:10.1002/ange.200805818Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). A Programmable DNA-Based Molecular Valve for Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 49(28), 4734-4737. doi:10.1002/anie.201000827Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). Ein programmierbares, DNA-basiertes molekulares Ventil für kolloidales, mesoporöses Siliciumoxid. Angewandte Chemie, 122(28), 4842-4845. doi:10.1002/ange.201000827Agostini, A., Mondragón, L., Pascual, L., Aznar, E., Coll, C., Martínez-Máñez, R., … Gil, S. (2012). Design of Enzyme-Mediated Controlled Release Systems Based on Silica Mesoporous Supports Capped with Ester-Glycol Groups. Langmuir, 28(41), 14766-14776. doi:10.1021/la303161eKresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. doi:10.1038/359710a0Knežević, N. Ž., & Durand, J.-O. (2015). Targeted Treatment of Cancer with Nanotherapeutics Based on Mesoporous Silica Nanoparticles. ChemPlusChem, 80(1), 26-36. doi:10.1002/cplu.201402369Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), 751-760. doi:10.1038/nnano.2007.387Petros, R. A., & DeSimone, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615-627. doi:10.1038/nrd2591Wagner, V., Dullaart, A., Bock, A.-K., & Zweck, A. (2006). The emerging nanomedicine landscape. Nature Biotechnology, 24(10), 1211-1217. doi:10.1038/nbt1006-1211Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 124(42), 10708-10712. doi:10.1002/ange.201204663Xie, M., Shi, H., Li, Z., Shen, H., Ma, K., Li, B., … Jin, Y. (2013). A multifunctional mesoporous silica nanocomposite for targeted delivery, controlled release of doxorubicin and bioimaging. Colloids and Surfaces B: Biointerfaces, 110, 138-147. doi:10.1016/j.colsurfb.2013.04.009Wang, Y., Shi, W., Song, W., Wang, L., Liu, X., Chen, J., & Huang, R. (2012). Tumor cell targeted delivery by specific peptide-modified mesoporous silica nanoparticles. Journal of Materials Chemistry, 22(29), 14608. doi:10.1039/c2jm32398bFerris, D. P., Lu, J., Gothard, C., Yanes, R., Thomas, C. R., Olsen, J.-C., … Zink, J. I. (2011). Synthesis of Biomolecule-Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells. Small, 7(13), 1816-1826. doi:10.1002/smll.201002300Tsai, C.-P., Chen, C.-Y., Hung, Y., Chang, F.-H., & Mou, C.-Y. (2009). Monoclonal antibody-functionalized mesoporous silica nanoparticles (MSN) for selective targeting breast cancer cells. Journal of Materials Chemistry, 19(32), 5737. doi:10.1039/b905158aBernardo, A. R., Cosgaya, J. M., Aranda, A., & Jiménez-Lara, A. M. (2013). Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death & Disease, 4(1), e479-e479. doi:10.1038/cddis.2013.5Patel, S., Sprung, A. U., Keller, B. A., Heaton, V. J., & Fisher, L. M. (1997). Identification of Yeast DNA Topoisomerase II Mutants Resistant to the Antitumor Drug Doxorubicin: Implications for the Mechanisms of Doxorubicin Action and Cytotoxicity. Molecular Pharmacology, 52(4), 658-666. doi:10.1124/mol.52.4.658Lyu, Y. L., Kerrigan, J. E., Lin, C.-P., Azarova, A. M., Tsai, Y.-C., Ban, Y., & Liu, L. F. (2007). Topoisomerase II  Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane. Cancer Research, 67(18), 8839-8846. doi:10.1158/0008-5472.can-07-1649Galluzzi, L., Vacchelli, E., Eggermont, A., Fridman, W. H., Galon, J., Sautès-Fridman, C., … Kroemer, G. (2012). Trial Watch. OncoImmunology, 1(5), 699-739. doi:10.4161/onci.20696Paone, A., Starace, D., Galli, R., Padula, F., De Cesaris, P., Filippini, A., … Riccioli, A. (2008). Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC- -dependent mechanism. Carcinogenesis, 29(7), 1334-1342. doi:10.1093/carcin/bgn14

    Drug-tubulin interactions interrogated by transient absorption spectroscopy

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    [EN] Colchicine (COL) is a bioactive molecule with antitumor properties. When COL binds to tubulin (TU), it inhibits microtubule assembly dynamics. We have investigated COL-TU interactions using laser flash photolysis (LFP) technique and performing fully flexible molecular dynamics simulations. Excitation of COL at 355 nm in aqueous medium did not lead to any transient absorption spectrum. By contrast, in the presence of TU a transient peaking at lambda(max) ca. 420 nm was registered and assigned as triplet excited COL complexed with TU ((COL)-C-3*@TU). In aerated medium, the lifetime was tau ca. 160 mu s and the quantum yield was 0.138. Likewise, when the bicyclic COL analog MTC was submitted to LFP in the presence of TU, (MTC)-M-3@TU* was detected with a lifetime of ca. 62 ms and a quantum yield of 0.296, Aqueous solutions of MTC did not produce any signal in the microsecond timescale. The triplet energy of MTC was obtained by means of emission measurements and found to be ca. 200 kJ mol(-1), a value that matches with that previously reported for COL (188 kJ mol(-1)). Molecular dynamic simulations, both with the ground and triplet excited state, reveal a strong interaction between COL and TU to give stabilized complexes with restricted mobility inside the protein binding site. These results demonstrate that LFP is a useful methodology to study the binding of COL derivatives to TU and open a new way to evaluate the interactions of non-fluorescent anticancer drugs with this protein.Financial support from the Spanish Government (grants CTQ2010-19909; BFU2011-23416 and SEV 2012-0267), the Generalitat Valenciana (Prometeo II/2013/005) and Comunidad de Madrid (S2010/BMD-2353) is gratefully acknowledged. G.S. thanks ASIC-UPV for computing time.Bosca Mayans, F.; Sastre Navarro, GI.; Andreu, JM.; Jornet, D.; Tormos Faus, RE.; Miranda Alonso, MÁ. (2015). Drug-tubulin interactions interrogated by transient absorption spectroscopy. RSC Advances. 5(61):49451-49458. https://doi.org/10.1039/C5RA05636ES4945149458561Mitchison, T., & Kirschner, M. (1984). Dynamic instability of microtubule growth. Nature, 312(5991), 237-242. doi:10.1038/312237a0Margolis, R. L., & Wilson, L. (1978). Opposite end assembly and disassembly of microtubules at steady state in vitro. Cell, 13(1), 1-8. doi:10.1016/0092-8674(78)90132-0Desai, A., & Mitchison, T. J. (1997). MICROTUBULE POLYMERIZATION DYNAMICS. Annual Review of Cell and Developmental Biology, 13(1), 83-117. doi:10.1146/annurev.cellbio.13.1.83Howard, J., & Hyman, A. A. (2003). Dynamics and mechanics of the microtubule plus end. Nature, 422(6933), 753-758. doi:10.1038/nature01600Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4(4), 253-265. doi:10.1038/nrc1317Ravelli, R. B. G., Gigant, B., Curmi, P. A., Jourdain, I., Lachkar, S., Sobel, A., & Knossow, M. (2004). Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature, 428(6979), 198-202. doi:10.1038/nature02393Cormier, A., Marchand, M., Ravelli, R. B. G., Knossow, M., & Gigant, B. (2008). Structural insight into the inhibition of tubulin by vinca domain peptide ligands. EMBO reports, 9(11), 1101-1106. doi:10.1038/embor.2008.171Prota, A. E., Bargsten, K., Diaz, J. F., Marsh, M., Cuevas, C., Liniger, M., … Steinmetz, M. O. (2014). A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. Proceedings of the National Academy of Sciences, 111(38), 13817-13821. doi:10.1073/pnas.1408124111Prota, A. E., Bargsten, K., Zurwerra, D., Field, J. J., Díaz, J. F., Altmann, K.-H., & Steinmetz, M. O. (2013). Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents. Science, 339(6119), 587-590. doi:10.1126/science.1230582Prota, A. E., Bargsten, K., Northcote, P. T., Marsh, M., Altmann, K.-H., Miller, J. H., … Steinmetz, M. O. (2014). Structural Basis of Microtubule Stabilization by Laulimalide and Peloruside A. Angewandte Chemie International Edition, 53(6), 1621-1625. doi:10.1002/anie.201307749Brossi, A., Yeh, H. J. C., Chrzanowska, M., Wolff, J., Hamel, E., Lin, C. M., … Silverton, J. (1988). Colchicine and its analogues: Recent findings. Medicinal Research Reviews, 8(1), 77-94. doi:10.1002/med.2610080105Imazio, M., Trinchero, R., & Adler, Y. (2008). Colchicine for the treatment of pericarditis. Future Cardiology, 4(6), 599-607. doi:10.2217/14796678.4.6.599Fakih, M., Replogle, T., Lehr, J. E., Pienta, K. J., & Yagoda, A. (1995). Inhibition of prostate cancer growth by estramustine and colchicine. The Prostate, 26(6), 310-315. doi:10.1002/pros.2990260606Lee, R. M., & Gewirtz, D. A. (2008). Colchicine site inhibitors of microtubule integrity as vascular disrupting agents. Drug Development Research, 69(6), 352-358. doi:10.1002/ddr.20267Abad, A., López-Pérez, J. L., del Olmo, E., García-Fernández, L. F., Francesch, A., Trigili, C., … San Feliciano, A. (2012). Synthesis and Antimitotic and Tubulin Interaction Profiles of Novel Pinacol Derivatives of Podophyllotoxins. Journal of Medicinal Chemistry, 55(15), 6724-6737. doi:10.1021/jm2017573Álvarez, R., Puebla, P., Díaz, J. F., Bento, A. C., García-Navas, R., de la Iglesia-Vicente, J., … Peláez, R. (2013). Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins. Journal of Medicinal Chemistry, 56(7), 2813-2827. doi:10.1021/jm3015603Panda, D., Daijo, J. E., Jordan, M. A., & Wilson, L. (1995). Kinetic Stabilization of Microtubule Dynamics at Steady State in Vitro by Substoichiometric Concentrations of Tubulin-Colchicine Complex. Biochemistry, 34(31), 9921-9929. doi:10.1021/bi00031a014Andreu, J. M., & Timasheff, S. N. (1982). Interaction of tubulin with single ring analogs of colchicine. Biochemistry, 21(3), 534-543. doi:10.1021/bi00532a019Roesner, M., Capraro, H.-G., Jacobson, A. E., Atwell, L., Brossi, A., Iorio, M. A., … Chignell, C. F. (1981). Biological effects of modified colchicines. Improved preparation of 2-demethylcolchicine, 3-demethylcolchicine, and (+)-colchicine and reassignment of the position of the double bond in dehydro-7-deacetamidocolchicines. Journal of Medicinal Chemistry, 24(3), 257-261. doi:10.1021/jm00135a005Pérez-Ramírez, B., Gorbunoff, M. J., & Timasheff, S. N. (1998). Linkages in Tubulin-Colchicine Functions:  The Role of the Ring C (C‘) Oxygens and Ring B in the Controls†. Biochemistry, 37(6), 1646-1661. doi:10.1021/bi971344dDUMORTIER, C., YAN, Q., BANE, S., & ENGELBORGHS, Y. (1997). Mechanism of tubulin–colchicine recognition: a kinetic study of the binding of the colchicine analogues colchicide and isocolchicine. Biochemical Journal, 327(3), 685-688. doi:10.1042/bj3270685Andreu, J. M., Gorbunopff, M. J., Lee, J. C., & Timasheff, S. N. (1984). Interaction of tubulin with bifunctional colchicine analogs: an equilibrium study. Biochemistry, 23(8), 1742-1752. doi:10.1021/bi00303a025Nguyen, T. L., McGrath, C., Hermone, A. R., Burnett, J. C., Zaharevitz, D. W., Day, B. W., … Gussio, R. (2005). A Common Pharmacophore for a Diverse Set of Colchicine Site Inhibitors Using a Structure-Based Approach. Journal of Medicinal Chemistry, 48(19), 6107-6116. doi:10.1021/jm050502tTorin Huzil, J., Winter, P., Johnson, L., Weis, A. L., Bakos, T., Banerjee, A., … Tuszynski, J. A. (2010). Computational Design and Biological Testing of Highly Cytotoxic Colchicine Ring A Modifications. Chemical Biology & Drug Design, 75(6), 541-550. doi:10.1111/j.1747-0285.2010.00970.xCao, R., Liu, M., Yin, M., Liu, Q., Wang, Y., & Huang, N. (2012). Discovery of Novel Tubulin Inhibitors via Structure-Based Hierarchical Virtual Screening. Journal of Chemical Information and Modeling, 52(10), 2730-2740. doi:10.1021/ci300302cLaing, N., Dahllöf, B., Hartley-Asp, B., Ranganathan, S., & Tew, K. D. (1997). Interaction of Estramustine with Tubulin Isotypes†. Biochemistry, 36(4), 871-878. doi:10.1021/bi961445wGireesh, K. K., Rashid, A., Chakraborti, S., Panda, D., & Manna, T. (2012). CIL-102 binds to tubulin at colchicine binding site and triggers apoptosis in MCF-7 cells by inducing monopolar and multinucleated cells. Biochemical Pharmacology, 84(5), 633-645. doi:10.1016/j.bcp.2012.06.008Gunasekera, N., Xiong, G., Musier-Forsyth, K., & Arriaga, E. (2004). A capillary electrophoretic method for monitoring the presence of α-tubulin in nuclear preparations. Analytical Biochemistry, 330(1), 1-9. doi:10.1016/j.ab.2004.03.059Medrano, F. J., Andreu, J. M., Gorbunoff, M. J., & Timasheff, S. N. (1991). Roles of ring C oxygens in the binding of colchicine to tubulin. Biochemistry, 30(15), 3770-3777. doi:10.1021/bi00229a026Morrison, K. C., & Hergenrother, P. J. (2012). Whole cell microtubule analysis by flow cytometry. Analytical Biochemistry, 420(1), 26-32. doi:10.1016/j.ab.2011.08.020Hastie, S. B., & Rava, R. P. (1989). Analysis of the near-ultraviolet absorption band of colchicine and the effect of tubulin binding. Journal of the American Chemical Society, 111(18), 6993-7001. doi:10.1021/ja00200a015Bhattacharyya, B., Kapoor, S., & Panda, D. (2010). Fluorescence Spectroscopic Methods to Analyze Drug–Tubulin Interactions. Microtubules, in vitro, 301-329. doi:10.1016/s0091-679x(10)95017-6Sardar, P. S., Maity, S. S., Das, L., & Ghosh, S. (2007). Luminescence Studies of Perturbation of Tryptophan Residues of Tubulin in the Complexes of Tubulin with Colchicine and Colchicine Analogues†. Biochemistry, 46(50), 14544-14556. doi:10.1021/bi701412kBhattacharyya, B., & Wolff, J. (1974). Promotion of Fluorescence upon Binding of Colchicine to Tubulin. Proceedings of the National Academy of Sciences, 71(7), 2627-2631. doi:10.1073/pnas.71.7.2627Lhiaubet-Vallet, V., Sarabia, Z., Boscá, F., & Miranda, M. A. (2004). Human Serum Albumin-Mediated Stereodifferentiation in the Triplet State Behavior of (S)- and (R)-Carprofen. Journal of the American Chemical Society, 126(31), 9538-9539. doi:10.1021/ja048518gVayá, I., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2014). Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems. Chem. Soc. Rev., 43(12), 4102-4122. doi:10.1039/c3cs60413fBosca, F., & Tormos, R. (2013). Behavior of Drug Excited States within Macromolecules: Binding of Colchicine and Derivatives to Albumin. The Journal of Physical Chemistry B, 117(25), 7528-7534. doi:10.1021/jp402489jFltzgerald, T. J. (1976). Molecular features of colchicine associated with antimitotic activity and inhibition of tubulin polymerization. Biochemical Pharmacology, 25(12), 1383-1387. doi:10.1016/0006-2952(76)90108-8Andreu, J. M. (2007). Large Scale Purification of Brain Tubulin With the Modified Weisenberg Procedure. Microtubule Protocols, 17-28. doi:10.1007/978-1-59745-442-1_2S. L. Murov , I.Carmichael and G. L.Hug, Handbook of Photochemistry, Marcel Dekker, Inc., New York, 2nd edn, 1993Silva, J. N., Bosca, F., Tomé, J. P. C., Silva, E. M. P., Neves, M. G. P. M. S., Cavaleiro, J. A. S., … Santus, R. (2009). Tricationic Porphyrin Conjugates: Evidence for Chain-Structure-Dependent Relaxation of Excited Singlet and Triplet States. The Journal of Physical Chemistry B, 113(52), 16695-16704. doi:10.1021/jp907930wLand, E. J. (1980). Pulse radiolysis and flash photolysis: some applications in biology and medicine. Biochimie, 62(4), 207-221. doi:10.1016/s0300-9084(80)80395-6Bensasson, R. V., & Gramain, J.-C. (1980). Benzophenone triplet properties in acetonitrile and water. Reduction by lactams. Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 76(0), 1801. doi:10.1039/f19807601801Plimpton, S. (1995). Fast Parallel Algorithms for Short-Range Molecular Dynamics. Journal of Computational Physics, 117(1), 1-19. doi:10.1006/jcph.1995.1039In ’t Veld, P. J., Plimpton, S. J., & Grest, G. S. (2008). Accurate and efficient methods for modeling colloidal mixtures in an explicit solvent using molecular dynamics. Computer Physics Communications, 179(5), 320-329. doi:10.1016/j.cpc.2008.03.005Rappe, A. K., Casewit, C. J., Colwell, K. S., Goddard, W. A., & Skiff, W. M. (1992). UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. Journal of the American Chemical Society, 114(25), 10024-10035. doi:10.1021/ja00051a040MOPAC2009, James J. P. Stewart, Stewart computational chemistry, version 13.207L; web: http://OpenMOPAC.netMaia, J. D. C., Urquiza Carvalho, G. A., Mangueira, C. P., Santana, S. R., Cabral, L. A. F., & Rocha, G. B. (2012). GPU Linear Algebra Libraries and GPGPU Programming for Accelerating MOPAC Semiempirical Quantum Chemistry Calculations. Journal of Chemical Theory and Computation, 8(9), 3072-3081. doi:10.1021/ct3004645Chai, J.-D., & Head-Gordon, M. (2008). Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections. Physical Chemistry Chemical Physics, 10(44), 6615. doi:10.1039/b810189bSchäfer, A., Huber, C., & Ahlrichs, R. (1994). Fully optimized contracted Gaussian basis sets of triple zeta valence quality for atoms Li to Kr. The Journal of Chemical Physics, 100(8), 5829-5835. doi:10.1063/1.467146Jacquemin, D., Wathelet, V., Perpète, E. A., & Adamo, C. (2009). Extensive TD-DFT Benchmark: Singlet-Excited States of Organic Molecules. Journal of Chemical Theory and Computation, 5(9), 2420-2435. doi:10.1021/ct900298eJacquemin, D., Perpète, E. A., Ciofini, I., & Adamo, C. (2010). Assessment of Functionals for TD-DFT Calculations of Singlet−Triplet Transitions. Journal of Chemical Theory and Computation, 6(5), 1532-1537. doi:10.1021/ct100005dPeach, M. J. G., Benfield, P., Helgaker, T., & Tozer, D. J. (2008). Excitation energies in density functional theory: An evaluation and a diagnostic test. The Journal of Chemical Physics, 128(4), 044118. doi:10.1063/1.2831900Bartovský, P., Tormos, R., & Miranda, M. A. (2009). Colchicine–protein interactions revealed by transient absorption spectroscopy after in situ photoisomerization to lumicolchicines. Chemical Physics Letters, 480(4-6), 305-308. doi:10.1016/j.cplett.2009.09.023Vayá, I., Bueno, C. J., Jiménez, M. C., & Miranda, M. A. (2008). Determination of Enantiomeric Compositions by Transient Absorption Spectroscopy using Proteins as Chiral Selectors. Chemistry - A European Journal, 14(36), 11284-11287. doi:10.1002/chem.200801657Marcus, Y. (1993). The properties of organic liquids that are relevant to their use as solvating solvents. Chemical Society Reviews, 22(6), 409. doi:10.1039/cs9932200409Nery, A. L. P., Quina, F. H., Moreira, Jr, P. F., Medeiros, C. E. R., Baader, W. J., Shimizu, K., … Bechara, E. J. H. (2001). Does the Photochemical Conversion of Colchicine into Lumicolchicines Involve Triplet Transients? A Solvent Dependence Study¶. Photochemistry and Photobiology, 73(3), 213. doi:10.1562/0031-8655(2001)0732.0.co;2Perdew, J. P., Burke, K., & Ernzerhof, M. (1996). Generalized Gradient Approximation Made Simple. Physical Review Letters, 77(18), 3865-3868. doi:10.1103/physrevlett.77.3865Perdew, J. P., Burke, K., & Ernzerhof, M. (1997). Generalized Gradient Approximation Made Simple [Phys. Rev. Lett. 77, 3865 (1996)]. Physical Review Letters, 78(7), 1396-1396. doi:10.1103/physrevlett.78.139

    Anions as Triggers in Controlled Release Protocols from Mesoporous Silica Nanoparticles Functionalized with Macrocyclic Copper(II) Complexes

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    Three different mesoporous silica nano-sized materials (SC1, SC2, and SC3), loaded with [Ru(bipy)(3)](2+) dye (bipy= bipyridine) and functionalized on the external surface with three macrocyclic copper(II) complexes (C1, C2, and C3), were synthesized and characterized. When SC1, SC2, and SC3 were suspended in water, the entrapped [Ru(bipy)(3)](2+) dye was free to diffuse from the inner pores to the solution. However, addition of anions induced certain degrees of pore blockage, with subsequent dye release inhibition. Small monovalent and divalent anions were unable to induce complete pore blockage, whereas bulky and highly charged anions induced marked reductions in [Ru(bipy)(3)](2+) delivery. The best [Ru(bipy)(3)](2+) delivery inhibitors were ATP and hexametaphosphate anions. Inhibition was ascribed to the interaction of the anions with the grafted Cu-II complexes on the surface of the SC1, SC2, and SC3 supports. The hexametaphosphate anion was selected to prepare two capped materials (SC1-mPh and SC3-mPh). Studies of the [Ru(bipy)(3)](2+) dye release from solids SC1-mPh and SC3-mPh alone and in the presence of a collection of selected anions (HS-, F-, Br-, Cl-, I-, CN-, HPO42-, AcO-, citrate, NO32-, HCO3-, SO42-, and S2O82-), amino acids (alanine and histidine), thiol-containing biomolecules (cysteine, methylcysteine, homocysteine, and glutathione (GSH)), and oxidants (H2O2) were performed. None of the chemicals tested, except hydrogen sulphide, was able to induce remarkable cargo delivery in both solids. The observed dye release was ascribed to a demetalation reaction of the C1 and C3 complexes induced by the hydrogen sulphide anion.Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEO/2009/016) is gratefully acknowledged.El Sayed Shehata Nasr, S.; Milani, M.; Milanese, C.; Licchelli, M.; Martínez-Máñez, R.; Sancenón Galarza, F. (2016). Anions as Triggers in Controlled Release Protocols from Mesoporous Silica Nanoparticles Functionalized with Macrocyclic Copper(II) Complexes. Chemistry - A European Journal. 22(39):13935-13945. https://doi.org/10.1002/chem.201601024S1393513945223

    Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems

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    [EN] The properties of singlet and triplet excited states are strongly medium-dependent. Hence, these species constitute valuable tools as reporters to probe compartmentalised microenvironments, including drug@protein supramolecular systems. In the present review, the attention is focused on the photophysical properties of the probe drugs (rather than those of the protein chromophores) using transport proteins (serum albumins and 1-acid glycoproteins) as hosts. Specifically, fluorescence measurements allow investigating the structural and dynamic properties of biomolecules or their complexes. Thus, the emission quantum yields and the decay kinetics of the drug singlet excited states provide key information to determine important parameters such as the stoichiometry of the complex, the binding constant, the relative degrees of occupancy of the different compartments, etc. Application of the FRET concept allows determining donor-acceptor interchromophoric distances. In addition, anisotropy measurements can be related to the orientation of the drug within the binding sites, where the degrees of freedom for conformational relaxation are restricted. Transient absorption spectroscopy is also a potentially powerful tool to investigate the binding of drugs to proteins, where formation of encapsulated triplet excited states is favoured over other possible processes leading to ionic species (i. e. radical ions), and their photophysical properties are markedly sensitive to the microenvironment experienced within the protein binding sites. Even under aerobic conditions, the triplet lifetimes of protein-complexed drugs are remarkably long, which provides a broad dynamic range for identification of distinct triplet populations or for chiral discrimination. Specific applications of the laser flash photolysis technique include the determination of drug distribution among the bulk solution and the protein binding sites, competition of two types of proteins to bind a 3 drug, occurrence of drug-drug interactions within protein binding sites, enzymatic-like activity of the protein or determination of enantiomeric compositions. The use of proteins as supramolecular hosts modifies the photoreactivity of encapsulated substrates by providing protection against oxygen or other external reagents, by imposing conformational restrictions in the binding pockets, or by influencing the stereochemical outcome. In this review, a selected group of examples is presented including decarboxylation, dehalogenation, nucleophilic addition, dimerisation, oxidation, Norrish type II reaction, photo-Fries rearrangement and 6 electrocyclisationFinancial support from the Spanish Government (CTQ2010-14882, JCI-2011-09926, RyC-2007-00476), from the EU (PCIG12-GA-2012-334257), from the Universitat Politènica de València (SP20120757) and from the Consellería de Educació, Cultura i Esport (PROMETEOII/2013/005, GV/2013/051) is gratefully acknowledged.Vayá Pérez, I.; Lhiaubet-Vallet, VL.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2014). Photoactive assemblies of organic compounds and biomolecules: drug-protein supramolecular systems. Chemical Society Reviews. 43:4102-4122. https://doi.org/10.1039/C3CS60413FS410241224

    Complexation and Chiral Recognition of Chiral Binaphthyl Derivatives and β

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    Caracterización fotofísica de compuestos con actividad antitumoral

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    Los bencimidazoles se usan como antihelmínticos, antinématodos y antiprotozoos. La colchicina es un alcaloíde tricíclico de orígen natural. Se ha usado en el tratamiento de gota, reumatismo y fiebre mediterránea. Recientemente, su actividad antitumoral ha generado expectativas en la investigación del cáncer. La actividad antitumoral de ambos tipos de compuestos se atribuye a su capacidad de influír en la polimerización de la tubulina y como consecuencia en el proceso de mitosis. El mecanismo preciso de acción no es conocido. Por esta razón proponemos utilizar la fotólisis de destello láser (FDL) para estudiar las interacciones entre los agentes antimitóticos en estado excitado con las proteínas y las ciclodextrinas. La FDL es una técnica relativamente novedosa y con muchas ventajas. En general, se conoce poco sobre los estados excitados singlete, mientras que los estados excitados triplete no han sido descritos. La fase preliminar ha consistido en la caracterización fotofísica y fotoquímicas de los compuestos cuyas propiedades no han sido estudiadas con anterioridad. Así, se han caracterizado el estado excitado triplete del 2-aminobencimidazol, del tiabendazol y de las lumicolchicinas (por generación in situ a través de la isomerización de la colchicina). Además, para el 2-aminobencimidazol, se ha identificado el radical aminilo, cuya formación ha sido utilizada como sonda en estudios mecanísticos llevados a cabo sobre la reactividad entre el triplete de distintas cetonas aromáticas y el 2-aminobencimidazol. Se ha valorado el uso de las especies transitorias de estos fármacos como sondas en el estudio de interacción con biomoléculas y ciclodextrinas. Así, se han estudiado las interacciones del triplete del tiabendazol con ciclodextrinas de distinto tamaño.Bartovsky ., P. (2011). Caracterización fotofísica de compuestos con actividad antitumoral [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11798Palanci

    Architectures matérielles pour filtres morphologiques avec des grandes éléments structurants

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    This thesis is focused on implementation of fundamental morphological filters in the dedicated hardware. The main objective of this thesis is to provide a programmable and efficient implementation of basic morphological operators using efficient dataflow algorithms considering the entire application point of view. In the first part, we study existing algorithms for fundamental morphological operators and their implementation on different computational platforms. We are especially interested in algorithms using the queue memory because their implementation provides the sequential data access and minimal latency, the properties very beneficial for the dedicated hardware. Then we propose another queue-based arbitrary-oriented opening algorithm that allows for direct granulometric measures. Performance benchmarks of these two algorithms are discussed, too. The second part presents hardware implementation of the efficient algorithms by means of stream processing units. We begin with 1-D dilation unit, then thanks to the separability of dilation we build up 2-D rectangular and polygonal dilation units. The processing unit for arbitrary-oriented opening and pattern spectrum is described as well. We also introduce a method of parallel computation using a few copies of processing units in parallel, thereby speeding up the computation. All proposed processing units are experimentally assessed in hardware by means of FPGA prototypes, and the performance and FPGA occupation results are discussed. In the third part, the proposed units are employed in two diverse applications illustrating thus their capability of addressing performance-demanding, low-power embedded applications. The main contributions of this thesis are: 1) new algorithm for arbitrary oriented opening and pattern spectrum, 2) programmable hardware implementation of fundamental morphological operators with large structuring elements and arbitrary orientation, 3) performance increase obtained through multi-level parallelism. Results suggest that the previously unachievable, real-time performance of these traditionally costly operators can be attained even for long concatenations and high-resolution imagesCette thèse se concentre sur la mise en œuvre d'implantations matérielles dédiées des filtres morphologiques fondamentaux, basés sur des itérations d'érosions/dilatations. L'objectif principal de cette thèse est de proposer une mise en oeuvre efficace et programmable de ces opérateurs en utilisant des algorithmes en flot de données et considérant les besoins applicatifs globaux. Dans la première partie, nous étudions les algorithmes existants pour les opérateurs morphologiques fondamentaux et leur réalisation sur des différentes plates-formes informatiques. Nous nous intéressons plus particulièrement à un algorithme basé sur la file d'attente pour la mise en œuvre de la dilatation car il permet de réaliser l'accès séquentiel aux données avec une latence minimale, ce qui est très favorable pour le matériel dédié. Nous proposons ensuite un autre algorithme réalisant l'ouverture morphologique, sous angle arbitraire, basé sur le même principe d'une file d'attente, permettant d'obtenir directement des mesures de granulométrie. La deuxième partie présente la mise en oeuvre matérielle des algorithmes efficaces au moyen d'unités de traitement à flot de données. Nous commençons par l'unité de dilatation 1-D, puis grâce à la séparabilité de la dilatation nous construisons des unités 2-D rectangulaire et polygonale. L'unité de traitement pour l'ouverture orientée et spectre modèle est ainsi décrit. Nous présentons également une méthode de parallélisation de calcul en dupliquant des unités de traitement. Toutes les unités de traitement proposés sont évalués expérimentalement par la réalisation des prototypes à base de circuits programmables (FPGA), et les résultats en termes d'occupation de surface et de vitesse de traitement sont discutées. Dans la troisième partie, les unités de calcul proposées sont utilisées dans deux applications différentes, illustrant ainsi leur capacité de répondre exigences des applications embarquées a basse consommation. Les principales contributions de cette thèse sont : i) proposition d'un nouvel algorithme d'ouverture sous angle arbitraire, ii) réalisation des architectures matérielles dédiées et programmables d'opérateurs morphologiques fondamentaux à l'élément structurant large et sous angle arbitraire ; iii) amélioration de la performance obtenue grâce à l'exploitation de plusieurs niveaux de parallélisme. Les résultats suggèrent que les performances de temps réel précédemment irréalisable de ces opérateurs traditionnellement coûteux peuvent être atteints même pour des longues concaténations d'opérateurs ou des images à haute résolutio

    One-scan algorithm for arbitrarily oriented 1-D morphological opening and slope pattern spectrum

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    International audienceThis paper presents a fast, one-scan algorithm for 1-D morphological opening on 2-D support. The algorithm is further extended to compute the pattern spectrum during a single image scan. The structuring element (SE) can be oriented under arbitrary angle that makes it possible to perform different orientation-involved image analysis, such as the local angle extraction, directional granulometry, etc. The algorithm processes an image in constant time regardless the SE orientation and size in one scan, with minimal latency and very low memory requirements. For pattern spectra, the C-implementation yields an experimental speed-up of 27× compared to other suitable solutions. Aforementioned properties allow for efficient implementation on hardware platforms such as GPU or FPGA that opens a new opportunity of parallel computation, and consequently, further speed-up
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