Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity

The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.

External and internal dynamics in the EU's counter-terrorism policy: a political and legal analysis

Tese de Doutoramento em Ciência Política e Relações Internacionais

Using mouse dynamics to assess stress during online exams

"Lecture notes in computer science series", ISSN 0302-9743, vol. 9121

Highly robust hydrogels via a fast, simple and cytocompatible dual crosslinking-based process

A highly robust hydrogel device made from a single biopolymer formulation is reported. Owing to the presence of covalent and non-covalent crosslinks, these engineered systems were able to (i) sustain a compressive strength of ca. 20 MPa, (ii) quickly recover upon unloading, and (iii) encapsulate cells with high viability rates.

Highly robust chitosan hydrogels via a fast, simple and biocompatible dual crosslinking-based process

Load-bearing soft tissues such as cartilage, blood vessels and muscles are able to withstand a remarkable compressive stress of several MPa without fracturing. Interestingly, most of these structural tissues are mainly composed of water and in this regard, hydrogels, as highly hydrated 3D-crosslinked polymeric networks, constitute a promising class of materials to repair lesions on these tissues. Although several approaches can be employed to shape the mechanical properties of artificial hydrogels to mimic the ones found on biotissues, critical issues regarding, for instance, their biocompatibility and recoverability after loading are often neglected. Therefore, an innovative hydrogel device made only of chitosan (CHI) was developed for the repair of robust biological tissues. These systems were fabricated through a dual-crosslinking process, comprising a photo- and an ionic-crosslinking step. The obtained CHIbased hydrogels exhibited an outstanding compressive strength of ca. 20 MPa at 95% of strain, which is several orders of magnitude higher than those of the individual components and close to the ones found in native soft tissues. Additionally, both crosslinking processes occur rapidly and under physiological conditions, enabling cellsâ encapsulation as confirmed by high cell survival rates (ca. 80%). Furthermore, in contrast with conventional hydrogels, these networks quickly recover upon unloading and are able to keep their mechanical properties under physiological conditions as result of their non-swell nature.

Fundamental concepts in multibody dynamics

In this chapter, the fundamental ingredients related to formulation of the equations of motion for multibody systems are described. In particular, aspects such as degrees of freedom, types of coordinates, basic kinematics joints and types of analysis in multibody systems are briefly characterized. Illustrative examples of application are also presented to better clarify the fundamental issues for spatial rigid multibody systems, which are of crucial importance in the formulation development of mathematical models of mechanical systems, as well as its computational implementation.

Introduction [to Contact force models for multibody dynamics]

"Series: Solid mechanics and its applications, vol. 226"

Numerical methods in multibody system dynamics

"Series: Solid mechanics and its applications, vol. 226"

Contact force models for multibody dynamics

"Series: Solid mechanics and its applications, vol. 226"

On the frictional contacts in multibody system dynamics

"Series title: Computational methods in applied sciences, ISSN1871-3033, vol. 42"

The electoral dynamics of human development

This paper analyses the impact of elections on the dynamics of human development in a panel of 82 countries over the period 1980-2013. The incidence of partisan and political support effects is also taken into account. A GMM estimator is employed in the empirical analysis and the results point out to the presence of an electoral cycle in the growth rate of human development. Majority governments also influence it, but no clear evidence is found regarding partisan effects. The electoral cycles have proved to be stronger in non-OECD countries, in countries with less frequent elections, with lower levels of income and human development, in presidential and non-plurality systems and in proportional representation regimes. They have also become more intense in this millennium.

Role of sirtuin 3 on mitochondrial dynamics in Huntington's disease striatal cells

Dissertação de mestrado em Genética Molecular

Development of a subject-specific musculoskeletal shoulder model : inverse and forward dynamics applications

A prevalência de pessoas que referem dor no complexo articular do ombro, com concomitante limitação na capacidade para realizar atividades da vida diária, é elevada. Estes níveis de prevalência sobrecarregam quer os utentes, como a própria sociedade. A evidência científica atual indicia a existência de uma relação entre as alterações da articulação escápulo-torácica e as patologias associadas à articulação gleno-umeral. A capacidade de quantificar, cinemática e cineticamente, as disfunções ao nível das articulações escápulo-torácica e gleno-umeral, é algo de enorme importância, quer para a comunidade biomecânica, como para a clínica. No decorrer dos trabalhos desta tese foi desenvolvido, através do software OpenSim, um modelo tridimensional músculo-esquelético do complexo articular do ombro que inclui a representação do tórax/coluna, clavícula, omoplata, úmero, rádio, cúbito e articulações que permitem os movimentos relativos desses segmentos, assim como, 16 músculos e 4 ligamentos. Com um total de 11 graus de liberdade, incluindo um novo modelo articular escápulo-torácico, os resultados demonstram que este é capaz de reconstruir de forma precisa e rápida os movimentos escápulo-torácicos e glenoumerais, recorrendo para tal, à cinemática inversa, e à dinâmica inversa e direta. Conta ainda com um método de transformação inovador para determinar, com base nas especificidades dos sujeitos, os locais de inserção muscular. As principais motivações subjacentes ao desenvolvimento desta tese foram contribuir para o aprofundar do atual conhecimento sobre as disfunções do complexo articular do ombro e, simultaneamente, proporcionar à comunidade clínica uma ferramenta biomecânica de livre acesso com o intuito de melhor suportar as decisões clínicas e dessa forma concorrer para uma prática mais efetiva.

Manipulación acustica del orden y dinámica molecular en estructuras mesomorficas de organización lamelar. Acoustic manipulation of molecular order and dynamics in mesomorphic structures of lamellar organization.

El control de propiedades hidrodinámicas capaces de influir en la mecánica de ruptura y poración de sistemas lamelares o membranas es de fundamental interés para diferentes aplicaciones biotecnológicas. Resulta de particular interés la conexión entre los procesos microscópicos relacionados al tipo de moléculas o unidades básicas, el orden determinado en el auto-ensamblado de las mismas y la dinámica local del sistema, con las propiedades físicas que determinan el comportamiento macroscópico bajo estimulación acústica. Resultados logrados recientemente sugieren la existencia de resonancias hidrodinámicas que podrian ser utilizadas para lograr la inestabilidad del sistema a baja potencia acústica. Se realizaran estudios experimentales utilizando principalmente técnicas que combinan resonancia magnética nuclear (RMN) y la sonicación de la muestra. También se realizarán estudios teóricos y simulaciones numéricas que permitan modelar los sistemas bajo estudio. Se propone dar continuidad al desarrollo de una técnica de relaxometría magnética nuclear en la cual se estimula acústicamente a la muestra durante el proceso de relajación magnética nuclear, y continuar la implementación de técnicas de RMN con resolución espacial que permitan complementar los estudios mencionados. Se espera comprender los mecanismos físicos que determinan la estabilidad de fases lamelares, logrando un modelo verificable y consistente que permita relacionar las propiedades mecánicas e hidrodinámicas con las propiedades de orden y dinámica molecular. Asimismo, se espera lograr avances en el desarrollo de las técnicas experimentales involucradas. La importancia del proyecto radica en el enfoque del problema. A diferencia de casi la totalidad de los estudios reportados, nuestro interés se enfoca en mecanismos de interacción entre la membrana y el campo acústico que sean eficientes a baja potencia acústica, en un régimen donde los gradientes térmicos y la cavitación sean despreciables.