625 research outputs found

    Near optimal configurations in mean field disordered systems

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    We present a general technique to compute how the energy of a configuration varies as a function of its overlap with the ground state in the case of optimization problems. Our approach is based on a generalization of the cavity method to a system interacting with its ground state. With this technique we study the random matching problem as well as the mean field diluted spin glass. As a byproduct of this approach we calculate the de Almeida-Thouless transition line of the spin glass on a fixed connectivity random graph.Comment: 13 pages, 7 figure

    Diminished Superoxide Generation Is Associated With Respiratory Chain Dysfunction and Changes in the Mitochondrial Proteome of Sensory Neurons From Diabetic Rats

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    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.OBJECTIVE Impairments in mitochondrial function have been proposed to play a role in the etiology of diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in axons of sensory neurons in type 1 diabetes is due to abnormal activity of the respiratory chain and an altered mitochondrial proteome. RESEARCH DESIGN AND METHODS Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in mitochondria from dorsal root ganglia (DRG) of control, 22-week-old streptozotocin (STZ)-diabetic rats, and diabetic rats treated with insulin. Rates of oxygen consumption and complex activities in mitochondria from DRG were measured. Fluorescence imaging of axons of cultured sensory neurons determined the effect of diabetes on mitochondrial polarization status, oxidative stress, and mitochondrial matrix-specific reactive oxygen species (ROS). RESULTS Proteins associated with mitochondrial dysfunction, oxidative phosphorylation, ubiquinone biosynthesis, and the citric acid cycle were downregulated in diabetic samples. For example, cytochrome c oxidase subunit IV (COX IV; a complex IV protein) and NADH dehydrogenase Fe-S protein 3 (NDUFS3; a complex I protein) were reduced by 29 and 36% (P < 0.05), respectively, in diabetes and confirmed previous Western blot studies. Respiration and mitochondrial complex activity was significantly decreased by 15 to 32% compared with control. The axons of diabetic neurons exhibited oxidative stress and depolarized mitochondria, an aberrant adaption to oligomycin-induced mitochondrial membrane hyperpolarization, but reduced levels of intramitochondrial superoxide compared with control. CONCLUSIONS Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.This work was supported by grants from the Juvenile Diabetes Research Foundation (#1-2008-280) and the National Institutes of Health to R.T.D. (grants NS-054847 and DK-073594). E.A. was supported by a grant from the National Science and Engineering Research Council (#3311686-06) to P.F. and subsequently by a postgraduate scholarship from the Manitoba Health Research Council. S.K.R.C. and E.Z. were supported by grants to P.F. from the Canadian Institutes for Health Research (#MOP-84214) and the Juvenile Diabetes Research Foundation (#1-2008-193). D.R.S. was supported by a grant to P.F. from the Manitoba Health Research Council. This work was also funded by the St. Boniface General Hospital and Research Foundation

    The mean field Ising model trough interpolating techniques

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    Aim of this work is not trying to explore a macroscopic behavior of some recent model in statistical mechanics but showing how some recent techniques developed within the framework of spin glasses do work on simpler model, focusing on the method and not on the analyzed system. To fulfil our will the candidate model turns out to be the paradigmatic mean field Ising model. The model is introduced and investigated with the interpolation techniques. We show the existence of the thermodynamic limit, bounds for the free energy density, the explicit expression for the free energy with its suitable expansion via the order parameter, the self-consistency relation, the phase transition, the critical behavior and the self-averaging properties. At the end a bridge to a Parisi-like theory is tried and discussed.Comment: 35 pages, no figur
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