A simple probabilistic construction yielding generalized entropies and divergences, escort distributions and q-Gaussians

We give a simple probabilistic description of a transition between two states which leads to a generalized escort distribution. When the parameter of the distribution varies, it defines a parametric curve that we call an escort-path. The R\'enyi divergence appears as a natural by-product of the setting. We study the dynamics of the Fisher information on this path, and show in particular that the thermodynamic divergence is proportional to Jeffreys' divergence. Next, we consider the problem of inferring a distribution on the escort-path, subject to generalized moments constraints. We show that our setting naturally induces a rationale for the minimization of the R\'enyi information divergence. Then, we derive the optimum distribution as a generalized q-Gaussian distribution

Flat Information Geometries in Black Hole Thermodynamics

The Hessian of either the entropy or the energy function can be regarded as a metric on a Gibbs surface. For two parameter families of asymptotically flat black holes in arbitrary dimension one or the other of these metrics are flat, and the state space is a flat wedge. The mathematical reason for this is traced back to the scale invariance of the Einstein-Maxwell equations. The picture of state space that we obtain makes some properties such as the occurence of divergent specific heats transparent.Comment: 14 pages, one figure. Dedicated to Rafael Sorkin's birthda

The Effect of Antioxidant Supplementation on Fatigue during Exercise: Potential Role for NAD+(H)

This study compared serum pyridine levels (NAD+ /NADH) in trained (n = 6) and untrained (n = 7) subjects after continuous progressive exercise at 50%, 70% then 95% of physical work capacity until fatigue (TTF) after consuming a placebo or antioxidant (AO) cocktail (Lactaway©). An increase of 17% in TTF was observed in AO as compared to placebo (p = 0.032). This was accompanied by a significant increase in serum NAD+ levels (p = 0.037) in the AO supplemented group post exercise. The increases in NAD+ and improved endurance reflect lower oxidative stress-induced suppression of aerobic respiration

Thermodynamic curvature and black holes

I give a relatively broad survey of thermodynamic curvature $R$, one spanning results in fluids and solids, spin systems, and black hole thermodynamics. $R$ results from the thermodynamic information metric giving thermodynamic fluctuations. $R$ has a unique status in thermodynamics as being a geometric invariant, the same for any given thermodynamic state. In fluid and solid systems, the sign of $R$ indicates the character of microscopic interactions, repulsive or attractive. $|R|$ gives the average size of organized mesoscopic fluctuating structures. The broad generality of thermodynamic principles might lead one to believe the same for black hole thermodynamics. This paper explores this issue with a systematic tabulation of results in a number of cases.Comment: 27 pages, 10 figures, 7 tables, 78 references. Talk presented at the conference Breaking of Supersymmetry and Ultraviolet Divergences in extended Supergravity, in Frascati, Italy, March 27, 2013. v2 corrects some small problem

Maximum-Entropy Weighting of Multi-Component Earth Climate Models

A maximum entropy-based framework is presented for the synthesis of projections from multiple Earth climate models. This identifies the most representative (most probable) model from a set of climate models -- as defined by specified constraints -- eliminating the need to calculate the entire set. Two approaches are developed, based on individual climate models or ensembles of models, subject to a single cost (energy) constraint or competing cost-benefit constraints. A finite-time limit on the minimum cost of modifying a model synthesis framework, at finite rates of change, is also reported.Comment: Inspired by discussions at the Mathematical and Statistical Approaches to Climate Modelling and Prediction workshop, Isaac Newton Institute for Mathematical Sciences, Cambridge, UK, 11 Aug. to 22 Dec. 2010. Accepted for publication in Climate Dynamics, 8 August 201

Geometro-thermodynamics of tidal charged black holes

Tidal charged spherically symmetric vacuum brane black holes are characterized by their mass m and tidal charge q, an imprint of the 5-dimensional Weyl curvature. For q>0 they are formally identical to the Reissner-Nordstr\"om black hole of general relativity. We study the thermodynamics and thermodynamic geometries of tidal charged black holes and discuss similarities and differences as compared to the Reissner-Nordstr\"om black hole. As a similarity, we show that (for q>0) the heat capacity of the tidal charged black hole diverges on a set of measure zero of the parameter space, nevertheless both the regularity of the Ruppeiner metric and a Poincar\'e stability analysis shows no phase transition at those points. The thermodynamic state spaces being different indicates that the underlying statistical models could be different. We find that the q<0 parameter range, which enhances the localization of gravity on the brane, is thermodynamically preferred. Finally we constrain for the first time the possible range of the tidal charge from the thermodynamic limit on gravitational radiation efficiency at black hole mergers.Comment: v3: 23 pages, 8 figures, 1 table, published versio

Metabolic Control Analysis in a Cellular Model of Elevated MAO-B: Relevance to Parkinson’s Disease

We previously demonstrated that spare respiratory capacity of the TCA cycle enzyme alpha-ketoglutarate dehydrogenase (KGDH) was completely abolished upon increasing levels of MAO-B activity in a dopaminergic cell model system (Kumar et al., J Biol Chem 278:46432–46439, 2003). MAO-B mediated increases in H2O2 also appeared to result in direct oxidative inhibition of both mitochondrial complex I and aconitase. In order to elucidate the contribution that each of these components exerts over metabolic respiratory control as well as the impact of MAO-B elevation on their spare respiratory capacities, we performed metabolic respiratory control analysis. In addition to KGDH, we assessed the activities and substrate-mediated respiration of complex I, pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and mitochondrial aconitase in the absence and presence of complex-specific inhibitors in specific and mixed substrate conditions in mitochondria from our MAO-B elevated cells versus controls. Data from this study indicates that Complex I and KGDH are the most sensitive to inhibition by MAO-B mediated H2O2 generation, and could be instrumental in determining the fate of mitochondrial metabolism in this cellular PD model system

The Effect of a ΔK280 Mutation on the Unfolded State of a Microtubule-Binding Repeat in Tau

Tau is a natively unfolded protein that forms intracellular aggregates in the brains of patients with Alzheimer's disease. To decipher the mechanism underlying the formation of tau aggregates, we developed a novel approach for constructing models of natively unfolded proteins. The method, energy-minima mapping and weighting (EMW), samples local energy minima of subsequences within a natively unfolded protein and then constructs ensembles from these energetically favorable conformations that are consistent with a given set of experimental data. A unique feature of the method is that it does not strive to generate a single ensemble that represents the unfolded state. Instead we construct a number of candidate ensembles, each of which agrees with a given set of experimental constraints, and focus our analysis on local structural features that are present in all of the independently generated ensembles. Using EMW we generated ensembles that are consistent with chemical shift measurements obtained on tau constructs. Thirty models were constructed for the second microtubule binding repeat (MTBR2) in wild-type (WT) tau and a ΔK280 mutant, which is found in some forms of frontotemporal dementia. By focusing on structural features that are preserved across all ensembles, we find that the aggregation-initiating sequence, PHF6*, prefers an extended conformation in both the WT and ΔK280 sequences. In addition, we find that residue K280 can adopt a loop/turn conformation in WT MTBR2 and that deletion of this residue, which can adopt nonextended states, leads to an increase in locally extended conformations near the C-terminus of PHF6*. As an increased preference for extended states near the C-terminus of PHF6* may facilitate the propagation of β-structure downstream from PHF6*, these results explain how a deletion at position 280 can promote the formation of tau aggregates

Aconitase Regulation of Erythropoiesis Correlates with a Novel Licensing Function in Erythropoietin-Induced ERK Signaling

Erythroid development requires the action of erythropoietin (EPO) on committed progenitors to match red cell output to demand. In this process, iron acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of erythroid progenitors. Aconitase enzymes have recently been identified as possible signal integration elements that couple erythropoiesis with iron availability. In the current study, a regulatory role for aconitase during erythropoiesis was ascertained using a direct inhibitory strategy.In C57BL/6 mice, infusion of an aconitase active-site inhibitor caused a hypoplastic anemia and suppressed responsiveness to hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition rapidly normalized red cell counts, but did not perturb other lineages. In primary erythroid progenitor cultures, aconitase inhibition impaired proliferation and maturation but had no effect on viability or ATP levels. This inhibition correlated with a blockade in EPO signal transmission specifically via ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a physical interaction between ERK and mitochondrial aconitase was identified and found to be sensitive to aconitase inhibition.Direct aconitase inhibition interferes with erythropoiesis in vivo and in vitro, confirming a lineage-selective regulatory role involving its enzymatic activity. This inhibition spares metabolic function but impedes EPO-induced ERK signaling and disturbs a newly identified ERK-aconitase physical interaction. We propose a model in which aconitase functions as a licensing factor in ERK-dependent proliferation and differentiation, thereby providing a regulatory input for iron in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an alternative to phlebotomy in the treatment of polycythemia vera

The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity

Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell’s change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cells. In this review, we will discuss the manifold roles that this TCA enzyme and its substrate play in cancer