1,571 research outputs found
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
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