Análisis del impacto socioeconómico de las zonas económicas de desarrollo especial como régimen aduanero en la ciudad de Esmeraldas.

Las Zonas Francas o ZEDES han sido utilizadas por las empresas que han querido reexportar sus productos, o terminar productos semi elaborados bajo el régimen de maquila, desde estos Regímenes Aduaneros; pero no han sido utilizadas como una herramienta de desarrollo de zonas deprimidas que requieren ser dotadas de plazas de trabajo inmediatas para evitar la migración hacia las grandes ciudades, cuyo resultado es el aumento de la población flotante y pobreza urbana. Las ZEDES, bajo su nuevo concepto de Régimen para el Desarrollo, pueden evitar esto. La Ciudad de Esmeraldas es privilegiada al contar con un puerto marítimo, a pesar de esto, este recurso no se ha explotado al máximo, se necesita fomentar la inversión para elevar las exportaciones y hacer que la balanza comercial sea favorable. Es por ello que se requiere de un estudio que permita visualizar de manera general las ventajas y desventajas que tiene la utilización de las zonas económicas de desarrollo especial como mecanismo de incentivo para la inversión y del crecimiento de las exportaciones. A su vez los efectos en la economía y la sociedad.Or ZEDES Free Trade Zones have been used by companies who wanted to re-export their products or semi-finished products under the maquila system, since these customs procedures; but they have not been used as a tool for development in depressed areas that require immediate equipped work spaces to prevent migration to the cities, resulting in the increase of floating population and urban poverty. The ZEDES, under its new concept of System Development, can prevent this. The Emerald City is privileged to have a seaport, although this resource has not been exploited to the full, we need to encourage investment to boost exports and make the trade balance is favorable. That is why it requires a study to visualize what the general advantages and disadvantages that the use of special economic zones development as an incentive mechanism for investment and export growth. In turn, the effects on the economy and society

Conformational dynamics associated with ligand binding to vertebrate hexa-coordinate hemoglobins

Neuroglobin (Ngb) and cytoglobin (Cygb) are two new additions to the globin family, exhibiting heme iron hexa-coordination, a disulfide bond and large internal cavities. These proteins are implicated in cytoprotection under hypoxic-ischemic conditions, but the molecular basis of their cytoprotective function is unclear. Herein, a photothermal and spectroscopic study of the interactions of diatomic ligands with Ngb, Cygb, myoglobin and hemoglobin is presented. The impact of the disulfide bond in Ngb and Cygb and role of conserved residues in Ngb His64, Val68, Cys55, Cys120 and Tyr44 on conformational dynamics associated with ligand binding/dissociation were investigated. Transient absorption and photoacoustic calorimetry studies indicate that CO photo-dissociation from Ngb leads to a volume expansion (13.4±0.9 mL mol-1), whereas a smaller volume change was determined for Ngb with reduced Cys (ΔV=4.6±0.3 mL mol-1). Furthermore, Val68 side chain regulates ligand migration between the distal pocket and internal hydrophobic cavities since Val68Phe geminate quantum yield is ∼2.7 times larger than that of WT Ngb. His64Gln and Tyr44Phe mutations alter the thermodynamic parameters associated with CO photo-release indicating that electrostatic/hydrogen binding network that includes heme propionate groups, Lys 67, His64, and Tyr 44 in Ngb modulates the energetics of CO photo-dissociation. In Cygb, CO escape from the protein matrix is fast (\u3c 40 ns) with a ΔH of 18±2 kcal mol-1 in Cygbred, whereas disulfide bridge formation promotes a biphasic ligand escape associated with an overall enthalpy change of 9±4 kcal mol-1. Therefore, the disulfide bond modulates conformational dynamics in Ngb and Cygb. I propose that in Cygb with reduced Cys the photo-dissociated ligand escapes through the hydrophobic tunnel as occurs in Ngb, whereas the CO preferentially migrates through the His64 gate in Cygbox. To characterize Cygb surface 1,8-ANS interactions with Cygb were investigated employing fluorescence spectroscopy, ITC and docking simulations. Two 1,8-ANS binding sites were identified. One binding site is located close to the extended N-terminus of Cygb and was also identified as a binding site for oleate. Furthermore, guanidinium hydrochloride-induced unfolding studies of Cygb reveal that the disulfide bond does not impact Cygb stability, whereas binding of cyanide slightly increases the protein stability

Abstract 196: Identification of small molecule inhibitors of the notch transcriptional activation complex

Abstract Deregulation of the Notch pathway underlies many aspects of cancer physiology depending on cell type and context. In many human cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of the neoplastic phenotype. Notch also plays a central role in cancer stem cells, which may underlie a role in metastasis and resistance to therapy. The important and diverse role played by Notch in cancer makes it an exceedingly attractive target for anti-neoplastic therapeutics. However, the full range of potential targets in the pathway have been under-explored. Through computer-aided drug design we explored potential ligand binding sites and screened for compounds that could disrupt the assembly of the Notch transcriptional activation complex. An in vitro assay that quantitatively measures the assembly of the Notch transcriptional complex on DNA was used for screening. We have recently reported the identification and characterization of a small molecule inhibitor of the Notch transcriptional activation complex, termed Inhibitor of Mastermind Recruitment-1 (IMR-1). Herein we report the characterization of small molecule inhibitors of Notch derived from IMR-1 that were identified through a combination of structure-activity relationship studies and molecular docking simulations. We demonstrate that these compounds inhibit the growth of Notch dependent cell lines and decrease Notch target gene transcription. Citation Format: Luisana Astudillo, Anthony Capobianco. Identification of small molecule inhibitors of the notch transcriptional activation complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 196. doi:10.1158/1538-7445.AM2017-19

Abstract A39: A small molecule inhibitor of the Notch transcriptional activation complex

Abstract Deregulation of the Notch pathway underlies many aspects of cancer physiology depending on cell type and context. In many human cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of the neoplastic phenotype. Notch also plays a central role in cancer stem cells, which may underlie a role in metastasis and resistance to therapy. The important and diverse role played by Notch in cancer makes it an exceedingly attractive target for anti-neoplastic therapeutics. However, the full range of potential targets in the pathway have been under-explored. To date, there are no small molecule inhibitors that directly target the intracellular Notch pathway or the assembly of the transcriptional activation complex. We have developed an in vitro assay that quantitatively measures the assembly of the Notch transcriptional complex on DNA. Through computer-aided drug design we explored potential ligand binding sites and screened for compounds that could disrupt the assembly of the Notch transcriptional activation complex. Herein we report the identification and characterization of a small molecule inhibitor of the Notch transcriptional activation complex, termed Inhibitor of Mastermind Recruitment-1 (IMR-1). We demonstrate that IMR-1 disrupts the recruitment of Mastermind-like 1 (Maml1) to the Notch transcriptional activation complex on chromatin and thereby causes a decrease in Notch target gene transcription. Furthermore, IMR-1 inhibits the growth of Notch-dependent cell lines and significantly abrogates the growth of patient-derived tumor xenografts. Therefore, our data suggest that a novel class of Notch inhibitors targeting the transcriptional activation complex may represent a new paradigm for Notch-based anticancer therapeutics. Citation Format: Luisana Astudillo, Anthony J. Capobianco. A small molecule inhibitor of the Notch transcriptional activation complex. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A39

Incidencia del desarrollo motriz en el aprendizaje de la escritura en niños de primer año de educación general básica del Jardín Rita Chávez de M.

En vista de que en los últimos tiempos, han proliferado los centros de desarrollo infantil, los cuales son instituciones previas al primero de básica; se encuentra la necesidad de averiguar cómo influyen en el desarrollo de la escritura de los niños de primero de básica del jardín Rita Chávez de M., enfocándose particularmente en el desarrollo motriz que tienen los niños y niñas al ingresar, y cómo su estancia en estos centros, los han ayudado para mejorar el nivel de desarrollo de sus habilidades grafo-motoras, que en un inicio se reflejan en el proceso de la escritura; también se considera que el desarrollo y el aprendizaje motriz deben seguir un orden facultativo secuencial, dentro del cual no se pueden saltar etapas ya que modificarían el desarrollo normal de los niños.Licenciado en Psicología Educativa, Especialización en Educación BásicaCuenc

Abstract A33: Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway

Abstract The Notch signaling pathway has been found to play an important role in multiple human cancers by regulating transcriptional programs. However, the mechanism by which Notch drives target gene transcription is still elusive. In our previous study, we have identified and characterized a novel Notch activation complex kinase, NACK, which acts as a Notch transcriptional co-activator and an essential regulator of Notch-mediated tumorigenesis and development. In this regard, NACK could become a putative drug target in anti-cancer therapies. The lack of three-dimensional (3D) structure of NACK hinders the designing of potential drug inhibitors. Therefore, computational methods are adopted to elucidate the structural and functional features of NACK, which further aid in designing new NACK inhibitors. Molecule docking (Glide) is utilized to obtain potential hit inhibitors for NACK, which will be validated using in-vitro and in-vivo assays. This will open avenues for the development of new therapies for Notch-dependent cancers. Citation Format: Xiaoxia Zhu, Zhiqiang Wang, Ke Jin, Luisana Astudillo, Wen Zhou, Jinshui Chen, Peter Buchwald, Stephan C. Schürer, Anthony J. Capobianco. Discovery of novel anti-cancer therapeutic agents for Notch activation complex kinase (NACK) targeting the Notch pathway. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A33