Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

Lamellarin D bioconjugates II: synthesis and cellular internalization of dendrimer and nuclear location signal derivatives

The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines(MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.

Lamellarin D bioconjugates I: synthesis and cellular internalization of PEG-derivatives

Herein is reported the design and synthesis of poly(ethylene glycol) derivatives of Lamellarin D with the aim of modulating their physicochemical properties, and improving the biological activity. Mono-, di- and tri-PEG conjugates with improved solubility were obtained in 18-57% overall yields from the corresponding partially protected phenolic derivatives of Lamellarin D. Conjugates 1-9 were tested in a panel of three human tumor cell lines (MDA-MB-231 breast, A-549 lung and HT-29 colon) to evaluate their cytotoxicity. Several compounds exhibited enhanced cellular internalization, and more than 85% of the derivatives showed a lower GI50 than Lam-D. Furthermore, cell cycle arrest at G2 phase, and apoptotic cell-death pathways were determined for Lamellarin D and these derivatives.

Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.

Estudo ab-initio da a-alanina em meio aquoso

Ab initio Hartree-Fock (HF), Density Functional (B3LYP) and electron correlation (MP2) methods have been used to caracterize the aqueous medium intramolecular hydrogen bond in a-alanine. The 6-31G* and 6-31++G** were taken from Gaussian94 library. We were concerned on the structure of three conformers of a-alanine, in their neutral form plus on the structure of the zwitterionic form (Z). The Z structure is a stationary point at the HF/6-31G* level but it is not when diffuse functions and electron correlation are included. This results shows that the Z form does not exist in the gas phase. The inclusion of solvent effects changed significantly the results obtained in gas phase, therefore this inclusion make the Z form a stationary point within all level of theory, and the relative energy depends dramatically on the level of calculation.

Estudio de mejora de la demanda energética de un edificio plurifamiliar de dos viviendas en Binéfar

El objetivo de este trabajo es realizar un estudio de mejora de la demanda energética de un edificio plurifamiliar de dos viviendas en Binéfar. Para ello, en este estudio pretende se analiza la demanda actual del edificio y se proponen una serie soluciones encaminadas a reducir y mejorar los valores de esta demanda poniendo en práctica los conocimientos adquiridos en las asignaturas de Construcción Sostenible de la titulación de Grado en Arquitectura Técnica.

TAPADÚ un lanzador de aplicaciones Android por voz

El objetivo final es construir una aplicación en Android que a través de un comando de voz inicie una aplicación. Por consiguiente es necesario crear una aplicación con una fuerte base en usabilidad y accesibilidad que permita configurar estos comandos de voz, que en adelante serán llamados rutina, y un widget que se encargue de escuchar al usuario para que inicie la aplicación tras escuchar el comando de voz. Además se añade la opción de guardar el catálogo de rutinas configuradas en un servidor externo, permitiendo descargar todas las rutinas configuradas en un nuevo dispositivo tras haberse logueado.

Usos retóricos del espacio público: la organización discursiva de un espacio en conflicto

En este artículo exploro la utilización discursiva del espacio público, entendido como un recurso retórico para la acción social localizada. A partir de extractos de documentos escritos y de entrevistas en profundidad, el análisis se centra en el uso retórico de formulaciones espaciales y construcciones de relaciones persona-lugar por parte de diversos agentes sociales e institucionales confrontados por la definición urbanística de un espacio en conflicto. La labor discursiva detectada incluye el manejo retórico de construcciones cultural e ideológicamente organizadas de la territorialidad urbana, usos argumentativos de categorías sociales localizadas y de guiones comportamentales para la elaboración de modos normativos de convivencia en el espacio público, y el empleo retórico de procesos simbólicos espacialmente arraigados. El propósito es contribuir a un examen crítico de los fenómenos socioespaciales conflictivos desde un enfoque discursivo, buscando visibilizar las tensiones sociales implicadas en el intento deliberado de controlar y ordenar el espacio urbano.

Estudio de errores en la localización en espacios interiores, de dispositivos móviles por medio de tecnologías WiFi

La localización en ambientes de interiores basada en dispositivos modernos de uso masivo, como los dispositivos móviles, es un área actual de investigación y desarrollo que ha empezado a generar productos para diferentes aplicaciones. Sin embargo, la estimación del error en estas mediciones, sus fuentes y la forma como se propaga, que evita tener mayor exactitud en la localización, aún presenta un área pendiente de estudio. Esta investigación toma una de las técnicas comunes de estudio de localización de dispositivos por redes inalámbricas WiFi para estudiar los diferentes errores que ella conlleva, sus fuentes y su propagación. Este trabajo también propone un nuevo enfoque y nueva metodología, que permite reducir el error en la localización de dispositivos WiFi, con base a la clasificación de las redes inalámbricas presentes en un escaneo, la identificación de muestras y datos fortuitos, la estabilización de muestreos de potencias de redes WiFi, y la implementación de un filtro de Kalman, para la predicción de medidas estables de estas potencias.

Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues

The autophagic process is a lysosomal degradation pathway, which is activated during stress conditions, such as starvation or exercise. Regular exercise has beneficial effects on human health, including neuroprotection. However, the cellular mechanisms underlying these effects are incompletely understood. Endurance and a single bout of exercise induce autophagy not only in brain but also in peripheral tissues. However, little is known whether autophagy could be modulated in brain and peripheral tissues by long-term moderate exercise. Here, we examined the effects on macroautophagy process of long-term moderate treadmill training (36 weeks) in adult rats both in brain (hippocampus and cerebral cortex) and peripheral tissues (skeletal muscle, liver and heart). We assessed mTOR activation and the autophagic proteins Beclin 1, p62, LC3B (LC3B-II/LC3B-I ratio) and the lysosomal protein LAMP1, as well as the ubiquitinated proteins. Our results showed in the cortex of exercised rats an inactivation of mTOR, greater autophagy flux (increased LC3-II/LC3-I ratio and reduced p62) besides increased LAMP1. Related with these effects a reduction in the ubiquitinated proteins was observed. No significant changes in the autophagic pathway were found either in hippocampus or in skeletal and cardiac muscle by exercise. Only in the liver of exercised rats mTOR phosphorylation and p62 levels increased, which could be related with beneficial metabolic effects in this organ induced by exercise. Thus, our findings suggest that long-term moderate exercise induces autophagy specifically in the cortex

Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues

The autophagic process is a lysosomal degradation pathway, which is activated during stress conditions, such as starvation or exercise. Regular exercise has beneficial effects on human health, including neuroprotection. However, the cellular mechanisms underlying these effects are incompletely understood. Endurance and a single bout of exercise induce autophagy not only in brain but also in peripheral tissues. However, little is known whether autophagy could be modulated in brain and peripheral tissues by long-term moderate exercise. Here, we examined the effects on macroautophagy process of long-term moderate treadmill training (36 weeks) in adult rats both in brain (hippocampus and cerebral cortex) and peripheral tissues (skeletal muscle, liver and heart). We assessed mTOR activation and the autophagic proteins Beclin 1, p62, LC3B (LC3B-II/LC3B-I ratio) and the lysosomal protein LAMP1, as well as the ubiquitinated proteins. Our results showed in the cortex of exercised rats an inactivation of mTOR, greater autophagy flux (increased LC3-II/LC3-I ratio and reduced p62) besides increased LAMP1. Related with these effects a reduction in the ubiquitinated proteins was observed. No significant changes in the autophagic pathway were found either in hippocampus or in skeletal and cardiac muscle by exercise. Only in the liver of exercised rats mTOR phosphorylation and p62 levels increased, which could be related with beneficial metabolic effects in this organ induced by exercise. Thus, our findings suggest that long-term moderate exercise induces autophagy specifically in the cortex

Monte Carlo simulation of x-ray emission by kilovolt electron bombardment

A physical model for the simulation of x-ray emission spectra from samples irradiated with kilovolt electron beams is proposed. Inner shell ionization by electron impact is described by means of total cross sections evaluated from an optical-data model. A double differential cross section is proposed for bremsstrahlung emission, which reproduces the radiative stopping powers derived from the partial wave calculations of Kissel, Quarles and Pratt [At. Data Nucl. Data Tables 28, 381 (1983)]. These ionization and radiative cross sections have been introduced into a general-purpose Monte Carlo code, which performs simulation of coupled electron and photon transport for arbitrary materials. To improve the efficiency of the simulation, interaction forcing, a variance reduction technique, has been applied for both ionizing collisions and radiative events. The reliability of simulated x-ray spectra is analyzed by comparing simulation results with electron probe measurements.

Introducción a las infraestructuras de datos espaciales

Este libro «Introducción a las Infraestructuras de Datos Espaciales» se plantea con esta finalidad, eminentemente didáctica, para explicar qué es una infraestructura de datos espaciales, qué aporta sobre, y como complementa a, los sistemas de información geográfica y, sobre todo, las bases tecnológicas, normativas y de especificaciones en las que se asienta. ...

L'efecte del canvi climàtic sobre els precursos de les aromes minoritàries del raïm

Aquest treball forma part d'un macroprojecte que pretén centrar-se en l'estudi de l'evolució dels precursos de les aromes minoritàries a la zona de la Rioja. Neix d'una inquietud que intenta esbrinar quins efectes globals té el canvi climàtic sobre les propietats químiques del raïm. Per tal de que es desenvolupi aquest projecte, prèviament es disposa d’un seguit de dades històriques i analítiques que permetran analitzar diferents paràmetres dels anys considerats com a anys d'estudi, que són 2009, 2010 i 2011. Els principals paràmetres que s'estudiaran són el GDD (Growing Degree Day) i la pluviometria, analitzant-los en tres collites diferents pels tres anys d’estudi , primer per separat i després junts per veure el seu efecte. Posteriorment, es farà un estudi més acurat de les diferents famílies químiques que hi ha, quina és la seva evolució així com, quines són les propietats químiques dels seus precursors minoritaris.

AulaCEP : experiencia de un entorno virtual de aprendizaje en un centro educativo presencial

En este trabajo se presenta un conjunto dereflexiones y conclusiones alrededor del proceso de formación del profesorado y personal no docente en el uso de un LMS (Learning Management System)en un centro educativo, y el proceso de implantación de dicho sistema. En el entorno presencial de aprendizaje del Centre d'Estudis Politècnics, en adelante CEP, es necesario facilitar la comunicación y el acceso a los recursos entre los miembros de la comunidad, no sólo por parte de los estudiantes para localizar recursos docentes y facilitar la comunicación con sus profesores, sino también para facilitar la reusabilidad e intercambio de los materiales, la comunicación entre docentes y el resto del personal del centro educativo, secretaria,administración, departamento de calidad y bolsa detrabajo, así como la interacción entre profesores y estudiantes y de éstos entre sí.