Perturbative analysis of disordered Ising models close to criticality

We consider a two-dimensional Ising model with random i.i.d. nearest-neighbor ferromagnetic couplings and no external magnetic field. We show that, if the probability of supercritical couplings is small enough, the system admits a convergent cluster expansion with probability one. The associated polymers are defined on a sequence of increasing scales; in particular the convergence of the above expansion implies the infinite differentiability of the free energy but not its analyticity. The basic tools in the proof are a general theory of graded cluster expansions and a stochastic domination of the disorder

Metastability for reversible probabilistic cellular automata with self--interaction

The problem of metastability for a stochastic dynamics with a parallel updating rule is addressed in the Freidlin--Wentzel regime, namely, finite volume, small magnetic field, and small temperature. The model is characterized by the existence of many fixed points and cyclic pairs of the zero temperature dynamics, in which the system can be trapped in its way to the stable phase. %The characterization of the metastable behavior %of a system in the context of parallel dynamics is a very difficult task, %since all the jumps in the configuration space are allowed. Our strategy is based on recent powerful approaches, not needing a complete description of the fixed points of the dynamics, but relying on few model dependent results. We compute the exit time, in the sense of logarithmic equivalence, and characterize the critical droplet that is necessarily visited by the system during its excursion from the metastable to the stable state. We need to supply two model dependent inputs: (1) the communication energy, that is the minimal energy barrier that the system must overcome to reach the stable state starting from the metastable one; (2) a recurrence property stating that for any configuration different from the metastable state there exists a path, starting from such a configuration and reaching a lower energy state, such that its maximal energy is lower than the communication energy

Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ(2). RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients

Relaxation Height in Energy Landscapes: an Application to Multiple Metastable States

The study of systems with multiple (not necessarily degenerate) metastable states presents subtle difficulties from the mathematical point of view related to the variational problem that has to be solved in these cases. We introduce the notion of relaxation height in a general energy landscape and we prove sufficient conditions which are valid even in presence of multiple metastable states. We show how these results can be used to approach the problem of multiple metastable states via the use of the modern theories of metastability. We finally apply these general results to the Blume--Capel model for a particular choice of the parameters ensuring the existence of two multiple, and not degenerate in energy, metastable states

Experimental assessment of a new form of scaling law for near-wall turbulence

Scaling laws and intermittency in the wall region of a turbulent flow are addressed by analyzing moderate Reynolds number data obtained by single component hot wire anemometry in the boundary layer of a flat plate. The paper aims in particular at the experimental validation of a new form of refined similarity recently proposed for the shear dominated range of turbulence, where the classical Kolmogorov-Oboukhov inertial range theory is inappropriate. An approach inspired to the extended self-similarity allows for the extraction of the different power laws for the longitudinal structure functions at several wall normal distances. A double scaling regime is found in the logarithmic region, confirming previous experimental results. Approaching the wall, the scaling range corresponding to the classical cascade-dominated range tends to disappear and, in the buffer layer, a single power law is found to describe the available range of scales. The double scaling is shown to be associated with two different forms of refined similarity. The classical form holds below the shear scale L s . The other, originally introduced on the basis of DNS data for a turbulent channel, is experimentally confirmed to set up above L s . Given the experimental diffulties in the evaluation of the instantaneous dissipation rate, some care is devoted to check that its one-dimensional surrogate does not bias the results. The increased intermittency as the wall is approached is experimentally found entirely consistent with the failure of the refined Kolmogorov-Oboukhov similarity and the establishment of its new form near the wall.Comment: 27 pages, 9 figure

From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs.

Oxidative stress can alter the expression level of many microRNAs (miRNAs), but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress-modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress-modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress-related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress-modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA-based gene regulation, oxidative stress signaling pathways, and autophagy

Assessment of the Effect of the Oral Iron Chelator Deferiprone on Asymptomatic Plasmodium Falciparum Parasitemia in Humans

While the parenteral iron-chelating agent desferrioxamine B has anti- malarial activity in humans, the usefulness of an orally active chelator for this indication has not been investigated previously in vivo. We conducted a prospective, double-blind, placebo-controlled, cross-over trial of deferiprone (L1; CP20; 1,2-dimethyl-3-hydroxypyridin-4-one) in 25 adult Zambians with asymptomatic Plasmodium falciparum parasitemia. Deferiprone was administered daily for three or four days in divided doses of 75 or 100 mg/kg of body weight, dosages that are effective for treating iron overload. No reduction in asexual intra-erythrocytic parasites was observed during or after deferiprone treatment. The mean peak plasma concentration of deferiprone (108.9 ± 24.9 μmol/L) achieved was within the range demonstrated to inhibit the growth of P. falciparum in vitro, but the systemic exposure as determined by the 24-hr plasma concentration-time curve would not be predicted inhibit growth in vivo. No evidence of deferiprone- associated hematological toxicity was noted in this short-term study of these subjects, all of whom had clinical evidence of normal body iron stores. Because of the risk of neutropenia and other adverse effects with higher doses or prolonged use of the chelator, additional trials of deferiprone as a sole anti-malarial agent would not seem to be justified. In contrast, further efforts are needed to develop other orally active iron-chelating agents specifically for their antimalarial action

Metastability and Nucleation for the Blume-Capel Model. Different mechanisms of transition

We study metastability and nucleation for the Blume-Capel model: a ferromagnetic nearest neighbour two-dimensional lattice system with spin variables taking values in -1,0,+1. We consider large but finite volume, small fixed magnetic field h and chemical potential "lambda" in the limit of zero temperature; we analyze the first excursion from the metastable -1 configuration to the stable +1 configuration. We compute the asymptotic behaviour of the transition time and describe the typical tube of trajectories during the transition. We show that, unexpectedly, the mechanism of transition changes abruptly when the line h=2*lambda is crossed.Comment: 96 pages, 44 tex-figures, 7 postscript figure

Critical droplets in Metastable States of Probabilistic Cellular Automata

We consider the problem of metastability in a probabilistic cellular automaton (PCA) with a parallel updating rule which is reversible with respect to a Gibbs measure. The dynamical rules contain two parameters $\beta$ and $h$ which resemble, but are not identical to, the inverse temperature and external magnetic field in a ferromagnetic Ising model; in particular, the phase diagram of the system has two stable phases when $\beta$ is large enough and $h$ is zero, and a unique phase when $h$ is nonzero. When the system evolves, at small positive values of $h$, from an initial state with all spins down, the PCA dynamics give rise to a transition from a metastable to a stable phase when a droplet of the favored $+$ phase inside the metastable $-$ phase reaches a critical size. We give heuristic arguments to estimate the critical size in the limit of zero ``temperature'' ($\beta\to\infty$), as well as estimates of the time required for the formation of such a droplet in a finite system. Monte Carlo simulations give results in good agreement with the theoretical predictions.Comment: 5 LaTeX picture