Experimental determination of the frequency and field dependence of Specific Loss Power in Magnetic Fluid Hyperthermia

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a promising therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different core diameter d= 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity of the applied alternating magnetic field H, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP=cH^x, with 2<x<3 for all samples. The x-value depends on sample size and field frequency/ intensity, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time Teff=19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency

Deglacial landform assemblage records fast ice-flow and retreat, Inner Hebrides, Scotland

High-resolution bathymetric data have been central to recent advances in the understanding of past dynamics of the former British–Irish Ice Sheet (BIIS). As approximately two-thirds of the former BIIS was probably marine-based during the Last Glacial Maximum (LGM) (c. 29–23 ka), geomorphic observations of the seabed are required increasingly to understand the extent, pattern and timing of past glaciation. Until recently, glacial reconstructions for the Inner Hebrides, offshore of western Scotland, have been based primarily on terrestrial observations. Previous workers have proposed generalized reconstructions in which the Inner Hebrides are located within a significant former ice-sheet flow pathway that drained the western Scottish sector of the BIIS, feeding the Barra Fan during the LGM and earlier glaciations (Fig. 1). Results from numerical ice-sheet modelling suggest that former ice-flow velocities within the region were on the order of hundreds to thousands of metres per year, but yield further insight by demonstrating how dynamic binge/purge cycles may have affected ice-sheet mass balance over time (Hubbard et al. 2009). Following the LGM, ice-sheet retreat through the area is estimated to have been in the order of 20 m per year (Clark et al. 2012). Here we present swath-bathymetric data from the Inner Hebrides that provide in situ constraints on ice-sheet flow and subsequent retreat dynamics from within this important sector of the BIIS

NMR and μ+\mu^{+}SR detection of unconventional spin dynamics in Er(trensal) and Dy(trensal) molecular magnets

Measurements of proton Nuclear Magnetic Resonance (1H NMR) spectra and relaxation and of Muon Spin Relaxation ($\mu^{+}$SR) have been performed as a function of temperature and external magnetic field on two isostructural lanthanide complexes, Er(trensal) and Dy(trensal) featuring crystallographically imposed trigonal symmetry. Both the nuclear 1/T1 and muon $\lambda$ longitudinal relaxation rates, LRR, exhibit a peak for temperatures T lower than 30K, associated to the slowing down of the spin dynamics, and the width of the NMR absorption spectra starts to increase significantly at T ca. 50K, a temperature sizably higher than the one of the LRR peaks. The LRR peaks have a field and temperature dependence different from those previously reported for all Molecular Nanomagnets. They do not follow the Bloembergen-Purcell-Pound scaling of the amplitude and position in temperature and field and thus cannot be explained in terms of a single dominating correlation time $\tau$c determined by the spin slowing down at low temperature. Further, for T lower than 50K the spectral width does not follow the temperature behavior of the magnetic susceptibility chi. We suggest, using simple qualitative considerations, that the observed behavior is due to a combination of two different relaxation processes characterized by the correlation times $\tau$LT and $\tau$HT, dominating for T lower than 30K and T higher than 50K, respectively. Finally, the observed flattening of LRR for T lower than 5K is suggested to have a quantum origin

Biophysical approaches for the study of interactions between molecular chaperones and protein aggregates.

Molecular chaperones are key components of the arsenal of cellular defence mechanisms active against protein aggregation. In addition to their established role in assisting protein folding, increasing evidence indicates that molecular chaperones are able to protect against a range of potentially damaging aspects of protein behaviour, including misfolding and aggregation events that can result in the generation of aberrant protein assemblies whose formation is implicated in the onset and progression of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The interactions between molecular chaperones and different amyloidogenic protein species are difficult to study owing to the inherent heterogeneity of the aggregation process as well as the dynamic nature of molecular chaperones under physiological conditions. As a consequence, understanding the detailed microscopic mechanisms underlying the nature and means of inhibition of aggregate formation remains challenging yet is a key objective for protein biophysics. In this review, we discuss recent results from biophysical studies on the interactions between molecular chaperones and protein aggregates. In particular, we focus on the insights gained from current experimental techniques into the dynamics of the oligomerisation process of molecular chaperones, and highlight the opportunities that future biophysical approaches have in advancing our understanding of the great variety of biological functions of this important class of proteins.We acknowledge financial support from the Frances and Augustus Newman Foundation (TPJK), the Biological Sciences Research Council (TPJK), the European Research Council (TPJK and MAW), the Wellcome Trust (CMD, TPJK and MV), and the Marie Curie fellowship scheme (PA).This is the final version of the article. It was first available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5CC03689

The census of nuclear activity of late-type galaxies in the Virgo cluster

The first spectroscopic census of AGNs associated to late-type galaxies in the Virgo cluster is carried on by observing 213 out of a complete set of 237 galaxies more massive than M_dyn>10^{8.5} solar masses. Among them, 77 are classified as AGNs (including 21 transition objects, 47 LINERs and 9 Seyferts), and comprize 32% of the late-type galaxies in Virgo. Due to spectroscopic incompleteness at most 21 AGNs are missed in the survey, so that the fraction would increase up to 41%. Using corollary Near-IR observations, that enable us to estimate galaxies dynamical masses, it is found that AGNs are hosted exclusively in massive galaxies, i.e. M_dyn\gsim 10^{10} solar masses. Their frequency increases steeply with the dynamical mass from zero at M_dyn\approx10^{9.5} solar masses to virtually 1 at M_dyn>10^{11.5} solar masses. These frequencies are consistent with the ones of low luminosity AGNs found in the general field by the SDSS. Massive galaxies that harbor AGNs commonly show conspicuous r-band star-like nuclear enhancements. Conversely they often, but not necessarily contain massive bulges. Few well known AGNs (e.g. M61, M100, NGC4535) are found in massive Sc galaxies with little or no bulge. The AGN fraction seems to be only marginally sensitive to galaxy environment. We infer the black hole masses using the known scaling relations of quiescent black holes. No black holes lighter than $\sim 10^6$ \msol are found active in our sample.Comment: The paper contains 13 figures and 5 tables; accepted for publication in MNRA

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Four domains for concurrency

AbstractWe give four domains for concurrency in a uniform way by means of domain equations. The domains are intended for modelling the four possible combinations of linear time versus branching time, and of interleaving versus noninterleaving concurrency. We use the linear time, noninterleaved domain to give operational and denotational semantics for a simple concurrent language with recursion, and prove that O = D