Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Asymptotically false-positive-maximizing attack on non-binary Tardos codes

We use a method recently introduced by Simone and Skoric to study accusation probabilities for non-binary Tardos fingerprinting codes. We generalize the pre-computation steps in this approach to include a broad class of collusion attack strategies. We analytically derive properties of a special attack that asymptotically maximizes false accusation probabilities. We present numerical results on sufficient code lengths for this attack, and explain the abrupt transitions that occur in these results

Emergence of stability in a stochastically driven pendulum: beyond the Kapitsa effect

We consider a prototypical nonlinear system which can be stabilized by multiplicative noise: an underdamped non-linear pendulum with a stochastically vibrating pivot. A numerical solution of the pertinent Fokker-Planck equation shows that the upper equilibrium point of the pendulum can become stable even when the noise is white, and the "Kapitsa pendulum" effect is not at work. The stabilization occurs in a strong-noise regime where WKB approximation does not hold.Comment: 4 pages, 7 figure

Thermal collapse of a granular gas under gravity

Free cooling of a gas of inelastically colliding hard spheres represents a central paradigm of kinetic theory of granular gases. At zero gravity the temperature of a freely cooling homogeneous granular gas follows a power law in time. How does gravity, which brings inhomogeneity, affect the cooling? We combine molecular dynamics simulations, a numerical solution of hydrodynamic equations and an analytic theory to show that a granular gas cooling under gravity undergoes thermal collapse: it cools down to zero temperature and condenses on the bottom of the container in a finite time.Comment: 4 pages, 12 eps figures, to appear in PR

Solution of a statistical mechanics model for pulse formation in lasers

We present a rigorous statistical-mechanics theory of nonlinear many mode laser systems. An important example is the passively mode-locked laser that promotes pulse operation when a saturable absorber is placed in the cavity. It was shown by Gordon and Fischer [1] that pulse formation is a first-order phase transition of spontaneous ordering of modes in an effective "thermodynamic" system, in which intracavity noise level is the effective temperature. In this paper we present a rigorous solution of a model of passive mode locking. We show that the thermodynamics depends on a single parameter, and calculate exactly the mode-locking point. We find the phase diagram and calculate statistical quantities, including the dependence of the intracavity power on the gain saturation function, and finite size corrections near the transition point. We show that the thermodynamics is independent of the gain saturation mechanism and that it is correctly reproduced by a mean field calculation. The outcome is a new solvable statistical mechanics system with an unstable self-interaction accompanied by a natural global power constraint, and an exact description of an important many mode laser system.Comment: 10 pages, 3 figures, RevTe

Velocity fluctuations of noisy reaction fronts propagating into a metastable state: testing theory in stochastic simulations

The position of a reaction front, propagating into a metastable state, fluctuates because of the shot noise of reactions and diffusion. A recent theory [B. Meerson, P.V. Sasorov, and Y. Kaplan, Phys. Rev. E 84, 011147 (2011)] gave a closed analytic expression for the front diffusion coefficient in the weak noise limit. Here we test this theory in stochastic simulations involving reacting and diffusing particles on a one-dimensional lattice. We also investigate a small noise-induced systematic shift of the front velocity compared to the prediction from the spatially continuous deterministic reaction-diffusion equation.Comment: 5 pages, 5 figure

Theory of the vortex matter transformations in high Tc superconductor YBCO

Flux line lattice in type II superconductors undergoes a transition into a "disordered" phase like vortex liquid or vortex glass, due to thermal fluctuations and random quenched disorder. We quantitatively describe the competition between the thermal fluctuations and the disorder using the Ginzburg -- Landau approach. The following T-H phase diagram of YBCO emerges. There are just two distinct thermodynamical phases, the homogeneous and the crystalline one, separated by a single first order transitions line. The line however makes a wiggle near the experimentally claimed critical point at 12T. The "critical point" is reinterpreted as a (noncritical) Kauzmann point in which the latent heat vanishes and the line is parallel to the T axis. The magnetization, the entropy and the specific heat discontinuities at melting compare well with experiments.Comment: 4 pages 3 figure

Extinction rates of established spatial populations

This paper deals with extinction of an isolated population caused by intrinsic noise. We model the population dynamics in a "refuge" as a Markov process which involves births and deaths on discrete lattice sites and random migrations between neighboring sites. In extinction scenario I the zero population size is a repelling fixed point of the on-site deterministic dynamics. In extinction scenario II the zero population size is an attracting fixed point, corresponding to what is known in ecology as Allee effect. Assuming a large population size, we develop WKB (Wentzel-Kramers-Brillouin) approximation to the master equation. The resulting Hamilton's equations encode the most probable path of the population toward extinction and the mean time to extinction. In the fast-migration limit these equations coincide, up to a canonical transformation, with those obtained, in a different way, by Elgart and Kamenev (2004). We classify possible regimes of population extinction with and without an Allee effect and for different types of refuge and solve several examples analytically and numerically. For a very strong Allee effect the extinction problem can be mapped into the over-damped limit of theory of homogeneous nucleation due to Langer (1969). In this regime, and for very long systems, we predict an optimal refuge size that maximizes the mean time to extinction.Comment: 26 pages including 3 appendices, 16 figure

On population extinction risk in the aftermath of a catastrophic event

We investigate how a catastrophic event (modeled as a temporary fall of the reproduction rate) increases the extinction probability of an isolated self-regulated stochastic population. Using a variant of the Verhulst logistic model as an example, we combine the probability generating function technique with an eikonal approximation to evaluate the exponentially large increase in the extinction probability caused by the catastrophe. This quantity is given by the eikonal action computed over "the optimal path" (instanton) of an effective classical Hamiltonian system with a time-dependent Hamiltonian. For a general catastrophe the eikonal equations can be solved numerically. For simple models of catastrophic events analytic solutions can be obtained. One such solution becomes quite simple close to the bifurcation point of the Verhulst model. The eikonal results for the increase in the extinction probability caused by a catastrophe agree well with numerical solutions of the master equation.Comment: 11 pages, 11 figure