2,539 research outputs found
Precision nanomedicines for prostate cancer
No full textEditorial. Published online: 27 February 2018Anna Cifuentes-Rius, Lisa M Butler and Nicolas H Voelcke
Energy Transfer Photoreactivity of Alkyl Azide Derivatives in Crystals
No full textBy Justin Cifuentes, Chemistry
Advisor: Anna Gudmundsdottir
Abstract: Upon irradiation, _, _, _, and _-alkyl azides form triplet ketone excited states which undergo further energy transfers to form triplet nitrenes as the intermediates. Laser flash photolysis studies show that the lifetimes of these triplet ketones and triplet nitrenes are longer in crystals than in solution. Nanocrystal suspension studies using water as the solvent were used to study the solid state. Solid state laser flash photolysis shows that the lifetimes of these triplet ketone azides and triplet nitrenes have increased in solid state. Through these explorations, it has been proposed that the crystal lattices function to control the stability of these intermediates
Maximizing RNA loading for gene silencing using porous silicon nanoparticles
No full textGene silencing by RNA interference is a powerful technology with broad applications. However, this technology has been hampered by the instability of small interfering RNA (siRNA) molecules in physiological conditions and their inefficient delivery into the cytoplasm of target cells. Porous silicon nanoparticles have emerged as a potential delivery vehicle to overcome these limitations-being able to encapsulate RNA molecules within the porous matrix and protect them from degradation. Here, key variables were investigated that influence siRNA loading into porous silicon nanoparticles. The effect of modifying the surface of porous silicon nanoparticles with various amino-functional molecules as well as the effects of salt and chaotropic agents in facilitating siRNA loading was examined. Maximum siRNA loading of 413 μg/(mg of porous silicon nanoparticles) was found when the nanoparticles were modified by a fourth generation polyamidoamine dendrimer. Low concentrations of urea or salt increased loading capacity: an increase in RNA loading by 19% at a concentration of 0.05 M NaCl or 21% at a concentration of 0.25 M urea was observed when compared to loading in water. Lastly, it was demonstrated that dendrimer-functionalized nanocarriers are able to deliver siRNA against ELOVL5, a target for the treatment of advanced prostate cancer.Terence Tieu, Sameer Dhawan, V. Haridas, Lisa M. Butler, Helmut Thissen, Anna Cifuentes-Rius, Nicolas H. Voelcke
El crepuscle de la filosofia
No full textEn el número 70 de la revista L'Espill trobaràs un dossier monogràfic sobre "El poder de les idees", amb contribucions de Blanca Garcés, Anna I. López, Marc Borràs, María José Murgui, José R. Ruiz Tamarit, Antonio Cubel, Mercè Rius, Rosa Mascarell, Antoni Martí Monterde i Adéla Kotátková, així com Cartes de Joan Fuster a Joan Sales, Josep M. Castellet, Santiago Albertí, Jordi Pujol i Montserrat Roig i una conversa amb Xavier Antich, per Francesc Viadel
El curs dels rius: La Tordera
No full textGrup de Recerca Medi Ambient i Tecnologies de la Informació GeogràficaLa Tordera és un dels rius més oblidats i maltractats de Catalunya, malgrat ésser-ne un dels més important
La promesa traicionada de la Europa social: del pleno empleo a la empleabilidad. Una mirada desde los paises del Sur Europa
No full textAnna Giulia Ingellis y Domenico Maddaloni reflexionan sobre la traición que el desmantelamiento de la Europa social ha supuesto para sus ciudadanos/as. Los autores identifican la base del creciente descontento hacia el proyecto europeo en la transformación de sus horizontes en términos de empleo. La gestión neoliberal predominante de la Gran Recesión que hemos vivido en la última década ha evaporado la vieja promesa europea de fortalecer los derechos sociales de sus ciudadanos/as teniendo como principal síntoma la defensa de la empleabilidad ante la garantía del pleno empleo. Según los autores, la responsabilización del individuo para su posición en el mercado laboral, en estos tiempos particularmente turbulentos, ha contribuido firmemente al crecimiento de una profunda desconfianza entre los ciudadanos/as hacia el papel beneficioso que Europa puede desempeñar en sus condiciones de vida
The general equation of δ direct methods and the novel SMAR algorithm residuals using the absolute value of ρ and the zero conversion of negative ripples
No full text"This paper is dedicated to the memory of Professor Carles Miravitlles".The general equation δM(r) = ρ(r) + g(r) of the δ direct methods (δ-GEQ) is established which, when expressed in the form δM(r) - ρ(r) = g(r), is used in the SMAR phasing algorithm [Rius (2020). Acta Cryst A76, 489-493]. It is shown that SMAR is based on the alternating minimization of the two residuals Rρ(χ) = ∫V [ρ(χ) - ρ(Φ)sρ]2 dV and Rδ(Φ) = ∫V mρ[δM(χ) - ρ(Φ)sρ]2 dV in each iteration of the algorithm by maximizing the respective Sρ(Φ) and Sδ(Φ) sum functions. While Rρ(χ) converges to zero, Rδ(Φ) converges, as predicted by the theory, to a positive quantity. These two independent residuals combine δM and ρ each with |ρ| while keeping the same unknowns, leading to overdetermination for diffraction data extending to atomic resolution. At the beginning of a SMAR phase refinement, the zero part of the mρ mask [resulting from the zero conversion of the slightly negative ρ(Φ) values] occupies ∼50% of the unit-cell volume and increases by ∼5% when convergence is reached. The effects on the residuals of the two SMAR phase refinement modes, i.e. only using density functions (slow mode) supplemented by atomic constraints (fast mode), are discussed in detail. Due to its architecture, the SMAR algorithm is particularly well suited for Deep Learning. Another way of using δ-GEQ is by solving it in the form ρ(r) = δM(r) - g(r), which provides a simple new derivation of the already known δM tangent formula, the core of the δ recycling phasing algorithm [Rius (2012). Acta Cryst. A68, 399-400]. The nomenclature used here is: (i) Φ is the set of φ structure factor phases of ρ to be refined; (ii) δM(χ) = FT-1{c(|E| - 〈|E|〉)×exp(iα)} with χ = {α}, the set of phases of |ρ| and c = scaling constant; (iii) mρ = mask, being either 0 or 1; sρ is 1 or -1 depending on whether ρ(Φ) is positive or negative.The following funding is acknowledged: Agencia Estatal de Investigación (grant Nos. PID2021-124734OB-C22 and CEX2023-001263-S). The author acknowledges the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2023-001263-S).Peer reviewe
Increasing data completeness in synchrotron tts-microdiffraction experiments for δ-recycling phasing of low-symmetry compounds
No full textSuccessful phasing of synchrotron through-the-substrate microdiffraction data by δ-recycling direct-methods largely depends on the number of missing intensities caused by the limited sample rotation range [J. Rius, Direct phasing from Patterson syntheses by δ recycling. Acta Cryst. A 2012, 68, 77–81]. Particularly, for the unfavorable triclinic system, dataset completeness resulting from a single series of consecutive ϕ-scans covering a total ϕ interval of ±35° is around 41%. This value is not enough for the routinary solution of a crystal structure by δ-recycling but can be increased by ~29% by applying the orthogonal χ strategy consisting of merging the information of two series of orthogonal ϕ-scans collected at the same microvolume of the polished thin section. Test calculations using simulated and experimental tts-data of the triclinic mineral axinite confirm that, with the help of the orthogonal χ strategy, crystal structures can be solved routinely. Since data in the ±35 ϕ-interval are normally accessible even for relatively thick glass-substrates (1–1.5 mm), a crystal structure can be determined from a single microvolume. For high-symmetry phases, due to the Laue symmetry redundancy, a single series of ϕ-scans normally suffices for the application of δ-recycling. However, when for experimental causes this series is incomplete, the orthogonal χ strategy also provides a simple way to increase the completeness which besides allowing solving the structure, is also beneficial for the subsequent refinement.Fil: Rius, Jordi. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia de los Materiales de Barcelona; EspañaFil: Vallcorba, Oriol. ALBA Synchrotron Light Source; EspañaFil: Crespi, Anna. Consejo Superior de Investigaciones Científicas. Instituto de Ciencia de los Materiales de Barcelona; EspañaFil: Colombo, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; Argentin
Tres buscadores de la chilenidad: Lenz, Laval y Vicuña Cifuentes
No full textThis collaboration is a synthesis of the contribution from the scholars Ramón Laval, Rodolfo Lenz and Julio Vicuña Cifuentes, to the knowledge of the chilean folk culture and his respective disciplinary development, with the support of the social sciences and the humanities. The author detachs that the work of this three investigators deliver a large and very important presentation of traditional goods, as basis to search ways for the comprehension of the chilean condition.Esta elaboración es una síntesis de las contribuciones de los eruditos Ramón Laval, Rodolfo Lenz y Julio Vicuña Cifuentes, al reconocimiento de la cultura folclórica y a su respectivo desarrollo disciplinario, con el apoyo de las ciencias sociales y de las humanidades. El autor destaca que la obra de estos tres investigadores entrega una amplia y muy importante presentación de bienes tradicionales, como base para buscar caminos de comprensión de la chilenidad
Tailoring Carbon Nanotubes Properties for Gene Delivery Applications
No full textLa teràpia gènica s’està convertit en una tècnica innovadora per tal de curar una malaltia mitjançant la inserció de gens dins les cèl•lules i òrgans d’un individu. El repte recau en l’alliberació eficient I segura de l’àcid nucleic terapèutic a les cèl•lules i òrgans objectiu. De tots els vectors sintètics desenvolupats recentment, els nanotubs de carboni són una elecció interessant que ja ha demostrat prometre considerablement com a sistema alliberació, gràcies a la seva proporció amplada-alçada i la seva capacitat de traspassar la membrana cel•lular. El problema que sorgeix és la seva limitada solubilització i l’agregació espontània in vivo.
Amb l’objectiu de desenvolupar nous dissenys basats en nanotubs de carboni per a la formació de complexos capaços de transfectar ADN a les cèl•lules, amb un a bon registre de biocompatibilitat i viabilitat cel•lular, s’han desenvolupat diferents estratègies. En primer lloc, s’ha optimitzat la funcionalització covalent dels nanotubs per mitjà de tècniques de plasma. Aquest tipus de modificació permet aconseguir tan superfícies altament reactives capaces d’unir ADN a través d’una molècula enllaçant, com superfícies carregades positivament que permeten l’envolcall de l’àcid nucleic per interacció electrostàtica. En segon lloc, s’ha avaluat la dispersió de nanotubs de diferents mides per mitjà d’un agent estabilitzant incloent un surfactant, un polímer amfifílic i proteïnes. Aquesta naturalesa química de la superfície del nanotub, juntament amb altres propietats físiques com ara l’allargada o el diàmetre, té un efecte directe en la dispersibilitat, citotoxicitat i biodistribució d’aquest sistemes.
L’ús de proteïnes per functionalitzar nanopartícules és encoratjador ja que forma la corona de proteïna a la seva superfície. Tals conjugats mostren una elevada capacitat de carregar ADN i permeten la regulació de la seva alliberació mitjançant la manipulació de la composició de la corona.La terapia génica se está convirtiendo en una técnica innovadora para curar enfermedades mediante la inserción de genes dentro de las células y órganos de un individuo. El reto recae en la liberación eficiente y segura de un acido nucleico terapéutico a los órganos objectivo. De todos los vectores sintéticos desarrollados recientemente, los nanotubos de carbono son una elección interesante que ya ha demostrado prometer considerablemente como sistema de liberación gracias a su proporción anchura-altura y su capacidad de traspasar la membrana celular. El problema que surge es su limitada solubilización i la agregación espontanea in vivo.
Con el objetivo de desarrollar nuevos diseños basados en nanotubos de carbono para la formación de complejos capaces te transfectar ADN a las células, con un buen registro de biocompatibilidad y viabilidad celular, se han desarrollado diferentes estrategias. En primer lugar, se ha optimizado la funcionalización covalente de los nanotubos por medio de técnicas de plasma. Este tipo de modificación permite conseguir tanto superficies altamente reactivas capaces de unir ADN a traves de una molécula enlazante, como cargadas positivamente que permiten el envoltorio del acido nucleico por interacción electrostática. En segundo lugar, se han evaluado la dispersión de nanotubos de medidas diferentes por mediado de un agente estabilizante que incluye un surfactante un polímero amfifílico y proteínas. Esta naturaleza química de la superficie del nanotubo, junto con otras propiedades físicas como su longitud o diámetro, tiene un efecto directo en la dispersibilidad, citotoxicidad y biodistribución de estos sitemas.
El uso de proteínas para funcionalizar nanopartículas es alentador ya que forma la corona de proteínas en su superficie. Dichos compuestos muestran una elevada capacidad de cargar ADN y permiten la regulación de su liberación mediante la manipulación de la composición de la corona.Gene therapy has become an increasing innovative technique to treat disease by the insertion of genes into individual’s cells and tissues. The challenge is to efficiently and safely deliver the therapeutic nucleic acid into the target cells and organs. Among the synthetic vectors recently developed, carbon nanotubes are an interesting choice as they have already demonstrated considerable promise as delivery systems due to their high aspect ratio and their capacity to translocate the cell membrane. The problem that arises is their limited solubilization and spontaneous aggregation in vivo.
Aiming to engineer new carbon nanotube-based designs for the formation of complexes able to transfect DNA/RNA to cells with a good track of biocompatibility and cell viability, different strategies have been developed. Firstly, the covalent functionalization of carbon nanotubes by plasma techniques has been optimized. This type of modification allows to either achieving highly reactive surfaces able to covalently bind DNA towards a chemical linker or a positively charged nanotube surface enabling the wrapping of the nucleic acid by electrostatic interaction. Secondly, the dispersion of the differently-sized carbon nanotubes by means of a stabilizing agent including a surfactant, an amphiphilic polymer and proteins has been assessed. The chemical nature of the modifying moieties on the carbon nanotube, alongside to other physical properties such as length or diameter, has a direct effect on the dispersibility, cytotoxicity and biodistribution of these systems.
The use of proteins in the nanoparticle functionalization is encouraging due to the formation of the protein corona on its surface. Such complex exhibits high DNA load capacities and allows a tunable payload release by manipulating the corona compositio
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