Generador de ofertas

Actualmente en TELSTAR SA el sistema de generación de ofertas se realiza de distintas formas dependiendo de la empresa que se trate. Una manera es a través de formularios creados en documentos Word, programados con macros escritas en Visual Basic. Otro modo es creando documentos a partir de ofertas similares, modificando su contenido de forma manual. Ante esta situación se hace necesario una mejora en el sistema de generación de ofertas de tal forma que este proceso sea más eficiente y –lo más importante- se eviten errores. Además, el sistema propuesto debe ser fácil de utilizar por las distintas partes implicadas en la confección de las propuestas de venta.

Arva: prospecciones en un centro productor de ánforas Dressel 20 (Alcolea del Río, Sevilla)

La campaña de excavación realizada en 1991 en las proximidades de sector termal de la ciudad romana de Arva (Alco1ea del Río, Sevilla) ha permitido localizar tres hornos dedicados a la producción de ánforas Dressel20. Uno de ellos se data en época flavio-trajanea; los dos restantes se sitúan en un momento post-severiano. El conjunto parece formar parte del sector artesanal de Arva, situado junto al Guadalquivir.

Arva: Prospección en un centro productor de ánforas Dressel 20 (Alcolea del Río, Sevilla)

La campaña de excavación realizada en 1991 en las proximidades de sector termal de la ciudad romana de Arva (Alco1ea del Río, Sevilla) ha permitido localizar tres hornos dedicados a la producción de ánforas Dressel20. Uno de ellos se data en época flavio-trajanea; los dos restantes se sitúan en un momento post-severiano. El conjunto parece formar parte del sector artesanal de Arva, situado junto al Guadalquivir.

Pla de màrqueting: Festivals and Events

La màster tesi consisteix en la creació i desenvolupament del pla de màrqueting del nou producte de Lloret Turisme i el Lloret Convention Bureau, el “Festivals & Events”. A la primera part del treball es fa una presentació de la metodologia seguida, de la presentació del cas, amb l’anàlisi de l’estat de la qüestió i la presentació de l’àmbit d’estudi. Seguidament es procedeix a desenvolupar el cos del treball, és a dir, les diferents parts del pla de màrqueting, així com el desenvolupament de la matriu de la base de dades pel nou producte “Festivals & Events” del Lloret Convention Bureau de Lloret de Mar

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.

Role of PheE15 gate in ligand entry and nitric oxide detoxification function of Mycobacterium tuberculosis truncated hemoglobin N

The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a potent nitric oxide dioxygenase (NOD) activity that allows it to relieve nitrosative stress and enhance in vivo survival of its host. Despite its small size, the protein matrix of HbN hosts a two-branched tunnel, consisting of orthogonal short and long channels, that connects the heme active site to the protein surface. A novel dual-path mechanism has been suggested to drive migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly by the short path, a ligand-induced conformational change regulates opening of the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as a gate. Site-directed mutagenesis and molecular simulations have been used to examine the gating role played by PheE15 in modulating the NOD function of HbN. Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and tryptophan have similar O(2)/CO association kinetics, but display significant reduction in their NOD function. Molecular simulations substantiated that mutation at the PheE15 gate confers significant changes in the long tunnel, and therefore may affect the migration of ligands. These results support the pivotal role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch in the oxygenated protein, and hence the NOD function of HbN.

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation.