Abstract basins of attraction

Abstract basins appear naturally in different areas of several complex variables. In this survey we want to describe three different topics in which they play an important role, leading to interesting open problems

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

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

Particle-Based Monte-Carlo Simulations of Steady-State Mass Transport at Intermediate Péclet Numbers

Conventional approaches for simulating steady-state distributions of dilute particles under diffusive and advective transport involve solving the diffusion and advection equations in at least two dimensions. Here, we present an alternative computational strategy by combining a particle-based rather than a field-based approach with the initialisation of particles in proportion to their flux. This method allows accurate prediction of the steady state and is applicable even at intermediate and high Péclet numbers (Pe>1) swhere traditional particle-based Monte-Carlo methods starting from randomly initialised particle distributions fail. We demonstrate that generating a flux of particles according to a predetermined density and velocity distribution at a single fixed time and initial location allows for accurate simulation of mass transport under flow. Specifically, upon initialisation in proportion to their flux, these particles are propagated individually and detected by summing up their Monte-Carlo trajectories in predefined detection regions. We demonstrate quantitative agreement of the predicted concentration profiles with the results of experiments performed with fluorescent particles in microfluidic channels under continuous flow. This approach is computationally advantageous and readily allows non-trivial initial distributions to be considered. In particular, this method is highly suitable for simulating advective and diffusive transport in microfluidic devices, for instance in the context of diffusive sizing.Financial support from the Biotechnology and Biological Sciences Research Council (BBSRC), the European Research Council (ERC), the Frances and Augustus Newman Foundation as well as the Swiss National Science Foundation is gratefully acknowledged

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

Synthesis and Biological Evaluation (in Vitro and in Vivo) of Cyclic RGD Peptidomimetic - Paclitaxel Conjugates Targeting Integrin alphaVbeta3

A small library of integrin ligand - Paclitaxel conjugates 10-13 was synthesized with the aim of using the tumor-homing cyclo[DKP-RGD] peptidomimetics for site-directed delivery of the cytotoxic drug. All the Paclitaxel-RGD constructs 10-13 inhibited biotinylated vitronectin binding to the purified alphaVbeta3 integrin receptor at low nanomolar concentration and showed in vitro cytotoxic activity against a panel of human tumor cell lines similar to that of Paclitaxel. Among the cell lines, the cisplatin-resistant IGROV-1/Pt1 cells expressed high levels of integrin alphaVbeta3, making them attractive to be tested in in vivo models. Cyclo[DKP-f3-RGD]-PTX 11 displayed sufficient stability in physiological solution and in both human and murine plasma to be a good candidate for in vivo testing. In tumor-targeting experiments against the IGROV-1/Pt1 human ovarian carcinoma xenotransplanted in nude mice, compound 11 exhibited a superior activity than Paclitaxel, despite the lower (ca. half) molar dosage used

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

Cyclic RGD peptidomimetics containing bifunctional diketopiperazine scaffolds as new potent integrin ligands

The synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3-diaminopropionic acid and aspartic acid (DKP-1-DKP-7) or glutamic acid (DKP-8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifunctional diketopiperazines were introduced into eight cyclic peptidomimetics containing the Arg-Gly-Asp (RGD) sequence. The resulting RGD peptidomimetics were screened for their ability to inhibit biotinylated vitronectin binding to the purified integrins \u3b1 v\u3b2 3 and \u3b1 v\u3b2 5, which are involved in tumor angiogenesis. Nanomolar IC 50 values were obtained for the RGD peptidomimetics derived from trans DKP scaffolds (DKP-2-DKP-8). Conformational studies of the cyclic RGD peptidomimetics by 1H NMR spectroscopy experiments (VT-NMR and NOESY spectroscopy) in aqueous solution and Monte Carlo/Stochastic Dynamics (MC/SD) simulations revealed that the highest affinity ligands display well-defined preferred conformations featuring intramolecular hydrogen-bonded turn motifs and an extended arrangement of the RGD sequence [C\u3b2(Arg)-C\u3b2(Asp) average distance 658.8 \uc5]. Docking studies were performed, starting from the representative conformations obtained from the MC/SD simulations and taking as a reference model the crystal structure of the extracellular segment of integrin \u3b1 v\u3b2 3 complexed with the cyclic pentapeptide, Cilengitide. The highest affinity ligands produced top-ranked poses conserving all the important interactions of the X-ray complex. Copyright \ua9 2012 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

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