In silico before in vivo: How to predict the heating efficiency of magnetic nanoparticles within the intracellular space

This work aims to demonstrate the need for in silico design via numerical simulation to produce optimal Fe 3 O 4 -based magnetic nanoparticles (MNPs) for magnetic hyperthermia by minimizing the impact of intracellular environments on heating efficiency. By including the relevant magnetic parameters, such as magnetic anisotropy and dipolar interactions, into a numerical model, the heating efficiency of as prepared colloids was preserved in the intracellular environment, providing the largest in vitro specific power absorption (SPA) values yet reported. Dipolar interactions due to intracellular agglomeration, which are included in the simulated SPA, were found to be the main cause of changes in the magnetic relaxation dynamics of MNPs under in vitro conditions. These results pave the way for the magnetism-based design of MNPs that can retain their heating efficiency in vivo, thereby improving the outcome of clinical hyperthermia experiments

Low-Dimensional Assemblies of Magnetic MnFe2O4 Nanoparticles and Direct In Vitro Measurements of Enhanced Heating Driven by Dipolar Interactions: Implications for Magnetic Hyperthermia

Magnetic fluid hyperthermia (MFH), the procedure of raising the temperature of tumor cells using magnetic nanoparticles (MNPs) as heating agents, has proven successful in treating some types of cancer. However, the low heating power generated under physiological conditions makes it necessary a high local concentration of MNPs at tumor sites. Here, we report how the in vitro heating power of magnetically soft MnFe2O4 nanoparticles can be enhanced by intracellular low-dimensional clusters through a strategy that includes: (a) the design of the MNPs to retain Neel magnetic relaxation in high-viscosity media, and (b) culturing MNP-loaded cells under magnetic fields to produce elongated intracellular agglomerates. Our direct in vitro measurements demonstrated that the specific loss power (SLP) of elongated agglomerates (SLP = 576 +/- 33 W/g) induced by culturing BV2 cells in situ under a dc magnetic field was increased by a factor of 2 compared to the SLP = 305 +/- 25 W/g measured in aggregates freely formed within cells. A numerical mean-field model that included dipolar interactions quantitatively reproduced the SLPs of these clusters both in phantoms and in vitro, suggesting that it captures the relevant mechanisms behind power losses under high-viscosity conditions. These results indicate that in situ assembling of MNPs into low-dimensional structures is a sound possible way to improve the heating performance in MFH

Carotid artery disease: Novel pathophysiological mechanisms identified by gene-expression profiling of peripheral blood

AbstractObjectThe pathogenesis of carotid artery stenosis (CAS) as well as the mechanisms underlying the different localisation of the atherosclerotic lesions remains poorly understood. We used microarray technology to identify novel systemic mediators that could contribute to CAS pathogenesis.Moreover, we compared gene-expression profile of CAS with that of patients affected by abdominal aortic aneurysm (AAA), previously published by our group.Methods and resultsBy global gene-expression profiling in a pool of 10 CAS patients and 10 matched controls, we found 82 genes differentially expressed. Validation study in pools used for profiling and replication study in larger numbers of CAS patients (n = 40) and controls (n = 40) of 14 genes by real-time polymerase chain reaction (RT-PCR) confirmed microarray results. Fourteen out of 82 genes were similarly expressed in AAA patients. Gene ontology analysis identified a statistically significant enrichment in CAS of differentially expressed transcripts involved in immune response and oxygen transport. Whereas alteration of oxygen transport is a common tract of the two localisations, alteration of immune response in CAS and of lipid metabolic process in AAA represents distinctive tracts of the two atherosclerotic diseases.ConclusionsWe describe the systemic gene-expression profile of CAS, which provides an extensive list of potential molecular markers

Diagnostic work-up of arrhythmogenic right ventricular cardiomyopathy by cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) has become a widespread diagnostic tool. Since its introduction, CMR has been used to image patients with a known or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC). Several abnormalities have been found and described by CMR and at present this diagnostic tool is considered very important for the diagnosis. However, the diagnosis of ARVC relies upon the fulfillment of both clinical and functional criteria and CMR can provide several but not all the information useful for the diagnosis. Furthermore, some findings such as evidence of right ventricular epicardial fat, once considered a peculiar marker of ARVC, have been shown to possess a low specificity. This document was prepared by representatives of the three Italian official Organizations involved in CMR. Its main scope is to highlight the problems encountered when studying patients with suspected ARVC at CMR, to indicate the basic technical equipment needed, to recommend a proper imaging protocol and to offer a consensus on the main features relevant for the diagnosis

Linking and causality in globally hyperbolic spacetimes

The linking number $lk$ is defined if link components are zero homologous. Our affine linking invariant $alk$ generalizes $lk$ to the case of linked submanifolds with arbitrary homology classes. We apply $alk$ to the study of causality in Lorentz manifolds. Let $M^m$ be a spacelike Cauchy surface in a globally hyperbolic spacetime $(X^{m+1}, g)$. The spherical cotangent bundle $ST^*M$ is identified with the space $N$ of all null geodesics in $(X,g).$ Hence the set of null geodesics passing through a point $x\in X$ gives an embedded $(m-1)$-sphere $S_x$ in $N=ST^*M$ called the sky of $x.$ Low observed that if the link $(S_x, S_y)$ is nontrivial, then $x,y\in X$ are causally related. This motivated the problem (communicated by Penrose) on the Arnold's 1998 problem list to apply link theory to the study of causality. The spheres $S_x$ are isotopic to fibers of $(ST^*M)^{2m-1}\to M^m.$ They are nonzero homologous and $lk(S_x,S_y)$ is undefined when $M$ is closed, while $alk(S_x, S_y)$ is well defined. Moreover, $alk(S_x, S_y)\in Z$ if $M$ is not an odd-dimensional rational homology sphere. We give a formula for the increment of \alk under passages through Arnold dangerous tangencies. If $(X,g)$ is such that $alk$ takes values in $\Z$ and $g$ is conformal to $g'$ having all the timelike sectional curvatures nonnegative, then $x, y\in X$ are causally related if and only if $alk(S_x,S_y)\neq 0$. We show that $x,y$ in nonrefocussing $(X, g)$ are causally unrelated iff $(S_x, S_y)$ can be deformed to a pair of $S^{m-1}$-fibers of $ST^*M\to M$ by an isotopy through skies. Low showed that if (\ss, g) is refocussing, then $M$ is compact. We show that the universal cover of $M$ is also compact.Comment: We added: Theorem 11.5 saying that a Cauchy surface in a refocussing space time has finite pi_1; changed Theorem 7.5 to be in terms of conformal classes of Lorentz metrics and did a few more changes. 45 pages, 3 figures. A part of the paper (several results of sections 4,5,6,9,10) is an extension and development of our work math.GT/0207219 in the context of Lorentzian geometry. The results of sections 7,8,11,12 and Appendix B are ne

Technical Note: The air quality modeling system Polyphemus

International audiencePolyphemus is an air quality modeling platform which aims at covering the scope and the abilities of modern air quality systems. It deals with applications from local scale to continental scale, using two Gaussian models and two Eulerian models. It manages passive tracers, radioactive decay, photochemistry and aerosol dynamics. The structure of the system includes four independent levels with data management, physical parameterizations, numerical solvers and high-level methods such as data assimilation. This enables sensitivity and uncertainty analysis, primarily through multimodel approaches. On top of the models, drivers implement advanced methods such as model coupling or data assimilation

On the computation of zone and double zone diagrams

Classical objects in computational geometry are defined by explicit relations. Several years ago the pioneering works of T. Asano, J. Matousek and T. Tokuyama introduced "implicit computational geometry", in which the geometric objects are defined by implicit relations involving sets. An important member in this family is called "a zone diagram". The implicit nature of zone diagrams implies, as already observed in the original works, that their computation is a challenging task. In a continuous setting this task has been addressed (briefly) only by these authors in the Euclidean plane with point sites. We discuss the possibility to compute zone diagrams in a wide class of spaces and also shed new light on their computation in the original setting. The class of spaces, which is introduced here, includes, in particular, Euclidean spheres and finite dimensional strictly convex normed spaces. Sites of a general form are allowed and it is shown that a generalization of the iterative method suggested by Asano, Matousek and Tokuyama converges to a double zone diagram, another implicit geometric object whose existence is known in general. Occasionally a zone diagram can be obtained from this procedure. The actual (approximate) computation of the iterations is based on a simple algorithm which enables the approximate computation of Voronoi diagrams in a general setting. Our analysis also yields a few byproducts of independent interest, such as certain topological properties of Voronoi cells (e.g., that in the considered setting their boundaries cannot be "fat").Comment: Very slight improvements (mainly correction of a few typos); add DOI; Ref [51] points to a freely available computer application which implements the algorithms; to appear in Discrete & Computational Geometry (available online

Magnetoresistance in Fe1−x_{1-x}Gax_x thin films presenting striped magnetic pattern: the role of closure domains and domain walls

In this work we show the existence of closure domains in Fe$_{1-x}$Ga$_x$ thin films featuring a striped magnetic pattern and study the effect of the magnetic domain arrangement on the magnetotransport properties. By means of X-ray resonant magnetic scattering, we experimentally demonstrate the presence of such closure domains and estimate their sizes and relative contribution to surface magnetization. Magnetotransport experiments show that the behavior of the magnetoresistance depends on the measurement geometry as well as on the temperature. When the electric current ows perpendicular to the stripe direction, the resistivity decreases when a magnetic field is applied along the stripe direction (negative magnetoresistance) in all the studied temperature range, and the calculations indicate that the main source is the anisotropic magnetoresistance. In the case of current flowing parallel to the stripe domains, the magnetoresistance changes sign, being positive at room temperature and negative at 100 K. To explain this behavior, the contribution to magnetoresistance from the domain walls must be considered besides the anisotropic one.Comment: 8 pages, 5 figure

Phenolic compounds in young developing kiwifruit in relation to light exposure: Implications for fruit calcium accumulation

The interaction between light availability and the biosynthesis of phenolic compounds in fruit of kiwifruit (Actinidia deliciosa var. deliciosa, C.F. Liang et A. R. Ferguson) was investigated. Fruits were exposed either to natural light or were artificially shaded while growing on mature vines and were analysed weekly during the first 11 weeks of development. Phenols were identified and quantified by using High Performance Liquid Chromatography (HPLC). Results showed that the predominant phenolic compounds were hydroxycinnamic acids (HCAs), flavonols and the flavan 3-ol epicatechin. Calcium (Ca2+), the main mineral nutrient involved in fruit quality was also determined. Light significantly increased the accumulation of both phenols and Ca2+ into the fruit. This work expands the list of known phenolics in kiwifruit and provides a possible explanation for the seasonal pattern of Ca2+ import into the fruit. Results on light–phenol interaction being apparently beneficial for fruit Ca2+ accumulation, suggest that accurate canopy management could enhance fruit quality