Hyperpolarized Long-T1 Silicon Nanoparticles for Magnetic Resonance Imaging

Silicon nanoparticles are experimentally investigated as a potential hyperpolarized, targetable MRI imaging agent. Nuclear T_1 times at room temperature for a variety of Si nanoparticles are found to be remarkably long (10^2 to 10^4 s) - roughly consistent with predictions of a core-shell diffusion model - allowing them to be transported, administered and imaged on practical time scales without significant loss of polarization. We also report surface functionalization of Si nanoparticles, comparable to approaches used in other biologically targeted nanoparticle systems.Comment: supporting material here: http://marcuslab.harvard.edu/Aptekar_hyper1_sup.pd

Science competitions using technology: a study of the behavior of the participating schools in the CNC in Portugal

Neste trabalho investiga-se a dinâmica de escolas do 3º ciclo do Ensino Básico em Portugal, na preparação e participação em uma competição desenvolvida em ambiente computacional sobre conteúdos curriculares de Matemática, Português, Físico-Química e Geologia. Foi realizada uma análise fatorial exploratória de dados empíricos relativos às 143 escolas participantes nas competições realizadas em 2015, analisando-se as suas caraterísticas de atuação. Foram identificados quatro fatores latentes descrevendo o comportamento das escolas: Treino quantitativo, Treino qualitativo, Prestação e Utilizadores, constatando-se que: (i) a participação na competição de Matemática é predominante; (ii) escolas participantes em duas ou três competições apresentam diferentes dinâmicas de preparação; (iii) escolas que participam apenas em Matemática e Físico-Química parecem adotar estratégias pedagógicas mais articuladas e eficientes. Reconhece-se que, embora as escolas participantes desenvolvam trabalhos de preparação, existe uma tendência para as escolas apresentarem estratégias distintas de atuação consoante a combinação de grupos disciplinares presentes nas competições oficiais.In this work we investigate the dynamics of 143 schools of the 3rd cycle of Basic Education in Portugal, regarding the preparation and participation in online science competitions on curricular contents of Mathematics, Portuguese, Physics and Chemistry and Geology. An exploratory factorial analysis of empirical data concerning the competitions in 2015 was carried out, to analyze the characteristics inherent to schools’ performance. Four latent factors describing the schools’ behavior were identified: Quantitative Training, Qualitative Training, Proficiency and Users, which allowed us to verify that: (i) participation in mathematics competition is predominant; (ii) schools participating in two or three competitions present different preparation dynamics; (iii) schools involved only in Mathematics and Physics and Chemistry competitions seem to adopt a more articulated and efficient pedagogical strategy. Although all schools develop a preparatory work before competitions, the strategies used seem to be related to the combination of distinct disciplinary groups participating in the competitions.Trabalho subsidiado por fundos portugueses através do Centro de Investigação e Desenvolvimento em Matemática e Aplicações (CIDMA) da Universidade de Aveiro, e da Fundação para a Ciência e a Tecnologia (FCT), dentro do projeto UID/MAT/04106/2013.publishe

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca(2+), suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens

Controlled Aggregation of Ferritin to Modulate MRI Relaxivity

Ferritin is an iron storage protein expressed in varying concentrations in mammalian cells. The deposition of ferric iron in the core of ferritin makes it a magnetic resonance imaging contrast agent, and ferritin has recently been proposed as a gene expression reporter protein for magnetic resonance imaging. To date, ferritin has been overexpressed in vivo and has been coexpressed with transferrin receptor to increase iron loading in cells. However, ferritin has a relatively low T2 relaxivity (R2 ≈ 1 mM−1s−1) at typical magnetic field strengths and so requires high levels of expression to be detected. One way to modulate the transverse relaxivity of a superparamagnetic agent is to cause it to aggregate, thereby manipulating the magnetic field gradients through which water diffuses. In this work, it is demonstrated by computer simulation and in vitro that aggregation of ferritin can alter relaxivity. The effects of aggregate size and intraaggregate perturber spacing on R2 are studied. Computer modeling indicates that the optimal spacing of the ferritin molecules in aggregate for increasing R2 is 100–200 nm for a typical range of water diffusion rates. Chemical cross-linking of ferritin at 12 Å spacing led to a 70% increase in R2 compared to uncross-linked ferritin controls. To modulate ferritin aggregation in a potentially biologically relevant manner, ferritin was attached to actin and polymerized in vitro. The polymerization of ferritin-F-actin caused a 20% increase in R2 compared to unpolymerized ferritin-G-actin. The R2-value was increased by another 10% by spacing the ferritin farther apart on the actin filaments. The modulation of ferritin aggregation by binding to cytoskeletal elements may be a useful strategy to make a functional reporter gene for magnetic resonance imaging