Cell bystander effect induced by radiofrequency electromagnetic fields and magnetic nanoparticles

Induced effects by direct exposure to ionizing radiation (IR) are a central issue in many fields like radiation protection, clinic diagnosis and oncological therapies. Direct irradiation at certain doses induce cell death, but similar effects can also occur in cells no directly exposed to IR, a mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce the death of cells loaded with MNPs in a focused oncological therapy known as magnetic hyperthermia. Indirect mechanisms are also able to induce the death of unloaded MNPs cells. Using in vitro cell models, we found that colocalization of the MNPs at the lysosomes and the non-increase of the temperature induces bystander effect under non-IR. Our results provide a landscape in which bystander effects are a more general mechanism, up to now only observed and clinically used in the field of radiotherapy.Comment: 16 pages, 4 figures, submitted to International Journal of Radiation Biolog

Probing the stability of superheavy dark matter particles with high-energy neutrinos

Two of the most fundamental properties of the dark matter particle, the mass and the lifetime, are only weakly constrained by the astronomical and cosmological evidence of dark matter. We derive in this paper lower limits on the lifetime of dark matter particles with masses in the range 10 TeV-10^15 TeV from the non-observation of ultrahigh energy neutrinos in the AMANDA, IceCube, Auger and ANITA experiments. For dark matter particles which produce neutrinos in a two body or a three body decay, we find that the dark matter lifetime must be longer than O(10^26-10^28) s for masses between 10 TeV and the Grand Unification scale. Finally, we also calculate, for concrete particle physics scenarios, the limits on the strength of the interactions that induce the dark matter decay.Comment: 17 pages, 6 figures; v2: references added, discussion improved, matches the version published at JCA

Application of magnetically induced hyperthermia on the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections

Magnetic hyperthermia is currently an EU-approved clinical therapy against tumor cells that uses magnetic nanoparticles under a time varying magnetic field (TVMF). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, since therapeutic drugs available display severe side effects and drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotely provoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nm were synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPs were added to Crithidia fasciculata choanomastigotes in exponential phase and incubated overnight. The amount of uploaded MNPs per cell was determined by magnetic measurements. Cell viability using the MTT colorimetric assay and flow cytometry showed that the MNPs were incorporated by the cells with no noticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) was applied to MNP-bearing cells, massive cell death was induced via a non-apoptotic mechanism. No effects were observed by applying a TVMF on control (without loaded MNPs) cells. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. Scanning Electron Microscopy showed morphological changes after TVMF experiments. These data indicate (as a proof of principle) that intracellular hyperthermia is a suitable technology to induce the specific death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies that combat parasitic infections.Comment: 9 pages, four supplementary video file

Uncertainties in gas kinematics arising from stellar continuum modelling in integral field spectroscopy data: the case of NGC2906 observed with MUSE/VLT

We study how the use of several stellar subtraction methods and line fitting approaches can affect the derivation of the main kinematic parameters (velocity and velocity dispersion fields) of the ionized gas component. The target of this work is the nearby galaxy NGC 2906, observed with the MUSE instrument at Very Large Telescope. A sample of twelve spectra is selected from the inner (nucleus) and outer (spiral arms) regions, characterized by different ionization mechanisms. We compare three different methods to subtract the stellar continuum (FIT3D, STARLIGHT and pPXF), combined with one of the following stellar libraries: MILES, STELIB and GRANADA+MILES. The choice of the stellar subtraction method is the most important ingredient affecting the derivation of the gas kinematics, followed by the choice of the stellar library and by the line fitting approach. In our data, typical uncertainties in the observed wavelength and width of the H\alpha and [NII] lines are of the order of _rms \sim 0.1\AA\ and _rms \sim 0.2\AA\ (\sim 5 and 10km/s, respectively). The results obtained from the [NII] line seem to be slightly more robust, as it is less affected by stellar absorption than H\alpha. All methods considered yield statistically consistent measurements once a mean systemic contribution \Delta\bar\lambda=\Delta\bar\sigma=0.2xDelta_{MUSE} is added in quadrature to the line fitting errors, where \Delta_{MUSE} = 1.1\AA\ \sim 50 km/s denotes the instrumental resolution of the MUSE spectra. Although the subtraction of the stellar continuum is critical in order to recover line fluxes, any method (including none) can be used in order to measure the gas kinematics, as long as an additional component of 0.2 x Delta_MUSE is added to the error budget.Comment: 20 pages, 14 figure

Constraints on the rare tau decays from mu --> e gamma in the supersymmetric see-saw model

It is now a firmly established fact that all family lepton numbers are violated in Nature. In this paper we discuss the implications of this observation for future searches for rare tau decays in the supersymmetric see-saw model. Using the two loop renormalization group evolution of the soft terms and the Yukawa couplings we show that there exists a lower bound on the rate of the rare process mu --> e gamma of the form BR(mu --> e gamma) > C BR(tau --> mu gamma) BR(tau --> e gamma), where C is a constant that depends on supersymmetric parameters. Our only assumption is the absence of cancellations among the high-energy see-saw parameters. We also discuss the implications of this bound for future searches for rare tau decays. In particular, for large regions of the mSUGRA parameter space, we show that present B-factories could discover either tau --> mu gamma or tau --> e gamma, but not both.Comment: 39 pages, 7 figures. Typos corrected, references adde

Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2+) or negative (COOH-) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.Comment: In Press. 33 pages, 11 figure

Computing with cells: membrane systems - some complexity issues.

Membrane computing is a branch of natural computing which abstracts computing models from the structure and the functioning of the living cell. The main ingredients of membrane systems, called P systems, are (i) the membrane structure, which consists of a hierarchical arrangements of membranes which delimit compartments where (ii) multisets of symbols, called objects, evolve according to (iii) sets of rules which are localised and associated with compartments. By using the rules in a nondeterministic/deterministic maximally parallel manner, transitions between the system configurations can be obtained. A sequence of transitions is a computation of how the system is evolving. Various ways of controlling the transfer of objects from one membrane to another and applying the rules, as well as possibilities to dissolve, divide or create membranes have been studied. Membrane systems have a great potential for implementing massively concurrent systems in an efficient way that would allow us to solve currently intractable problems once future biotechnology gives way to a practical bio-realization. In this paper we survey some interesting and fundamental complexity issues such as universality vs. nonuniversality, determinism vs. nondeterminism, membrane and alphabet size hierarchies, characterizations of context-sensitive languages and other language classes and various notions of parallelism