Mechanism of transport of saquinavir-loaded nanostructured lipid carriers across the intestinal barrier

[EN] The aims of this work were (i) to evaluate the potential of nanostructured lipid carriers (NLCs) as a tool to 24 enhance the oral bioavailability of poorly soluble compounds using saquinavir (SQV), a BCS class IV drug 25 and P-gp substrate as a model drug, and (ii) to study NLC transport mechanisms across the intestinal barrier. 26 Three different NLC formulations were evaluated. SQV transport across Caco-2 monolayers was enhanced up 27 to 3.5-fold by NLCs compared to SQV suspension. M cells did not enhance the transport of NLCs loaded with 28 SQV. The size and amount of surfactant in the NLCs influenced SQV's permeability, the transcytosis pathway 29 and the efflux of SQV by P-gp. An NLC of size 247 nm and 1.5% (w/v) surfactant content circumvented P-gp 30 efflux and used both caveolae- and clathrin-mediated transcytosis, in contrast to the other NLC formulations, 31 which used only caveolae-mediated transcytosis. By modifying critical physicochemical parameters of the 32 NLC formulation, we were thus able to overcome the P-gp drug efflux and alter the transcytosis mechanism 33 of the nanoparticles. These findings support the use of NLCs approaches for oral delivery of poorly 34 water-soluble P-gp substrates.

Trends in Income and Price Elasticities of Transport Demand (1850-2010)

40 p.

Dieta de la nutria (Lutra lutra) en un tramo fluvial : variación estacional.

Se estudió la dieta de la nutria (Lutra lutra Linnaeus 1758) mediante análisis de restos fecales, en un tramo del río Nela (Burgos), un afluente del Ebro, durante tres distintas épocas de un año (Octubre, Diciembre y Abril). La presencia de cada presa se expresó en porcentaje de peso seco con respecto al total. Se comprobó que la dieta de la nutria se compone principalmente de cangrejo señal Pacifastacus leniusculus Dana, 1852 (88,99 ± 21,52%), seguida por peces (8,23 ± 21,15%), siendo las demás presas (insectos, anfibios, moluscos y materia vegetal) poco importantes, por lo que la mayor parte de la investigación se centró en estos dos tipos de presas. Se encontraron diferencias significativas en la composición de la dieta en octubre (Cangrejo: 97,2 ± 3,72%; Pez: 0,94 ± 2,88%), diciembre (Cangrejo: 67,68 ± 32,13%; Pez: 27,03 ± 33,77%) y abril (Cangrejo: 97,25 ± 3,62%; Pez: 1,06 ± 1,38%), siendo diciembre la época en la que mayor diversidad presentó su dieta. Las estimaciones de número de cangrejos ingeridos fueron apoyadas por un análisis de las piezas reconocibles de los mismos, para estimar el número mínimo de individuos presentes en un excremento. Por otro lado, se estimaron, a partir de medidas de arcos faríngeos, cleitros y opérculos encontrados en los excrementos, la longitud y el peso estimados de los peces que componían su dieta, como Parachondrostoma miegii (Steindachner, 1866), Gobio gobio Linnaeus, 1758 y Luciobarbus graellsii (Steindachner, 1866), Phoxinus phoxinus Linnaeus, 1758 y Alburnus alburnus Linnaeus, 1758, siendo estos dos últimos las especies dominantes en las muestras de peces (P. phoxinus: 52,3%, N= 45; A. alburnus: 32,5%).

Charge and spin transport in graphene devices

170 p.

Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport

Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.

Análisis de viabilidad de un proyecto empresarial vinculado al transporte fluvial

En este informe se analiza y comprueba la viabilidad económico-financiera de un proyecto empresarial para la prestación de un servicio de transporte fluvial de personas por la ría de Bilbao. Este proyecto consiste en el transporte de personas a lo largo de la ría del Nervión utilizando dos buques. El recorrido abarca desde el Casco Viejo de Bilbao hasta la terminal de cruceros de Las Arenas.

Quantum Simulator for Transport Phenomena in Fluid Flows

Transport phenomena still stand as one of the most challenging problems in computational physics. By exploiting the analogies between Dirac and lattice Boltzmann equations, we develop a quantum simulator based on pseudospin-boson quantum systems, which is suitable for encoding fluid dynamics transport phenomena within a lattice kinetic formalism. It is shown that both the streaming and collision processes of lattice Boltzmann dynamics can be implemented with controlled quantum operations, using a heralded quantum protocol to encode non-unitary scattering processes. The proposed simulator is amenable to realization in controlled quantum platforms, such as ion-trap quantum computers or circuit quantum electrodynamics processors.

Charge and spin transport in nanoscale devices

137 p.