A novel proviral clone of HIV-2: Biological and phylogenetic relationship to other primate immunodeficiency viruses.

Infectious molecular clones of the human immunodeficiency virus type 2 (HIV-2) will be valuable tools for the study of regulatory gene functions and the development of an animal model for the human acquired immunodeficiency syndrome (AIDS). To this end, we have cloned and sequenced a novel HIV-2 isolate, HIV-2BEN. One clone, designated MK6, is infectious for various human T-cell lines and for human and macaque peripheral blood lymphocytes (PBL), allowing molecular studies of HIV-2 infection and replication. Since MK6 is highly cytopathic in MT-2 and Molt-4 clone 8 cells, antiviral agents and neutralizing sera may be tested. Cluster analysis of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) env and gag genes revealed that HIV-2BEN yielded the earliest node of phylogenetic divergence for all reported HIV-2 sequences. Noise analysis showed that, with the current data, no specification of any branching order can be made among the four groups of primate lentiviruses, HIV-1, HIV-2/SIVSMM/MAC, SIVAGM, and SIVMND

Stochastics theory of log-periodic patterns

We introduce an analytical model based on birth-death clustering processes to help understanding the empirical log-periodic corrections to power-law scaling and the finite-time singularity as reported in several domains including rupture, earthquakes, world population and financial systems. In our stochastics theory log-periodicities are a consequence of transient clusters induced by an entropy-like term that may reflect the amount of cooperative information carried by the state of a large system of different species. The clustering completion rates for the system are assumed to be given by a simple linear death process. The singularity at t_{o} is derived in terms of birth-death clustering coefficients.Comment: LaTeX, 1 ps figure - To appear J. Phys. A: Math & Ge

Anomalous diffusion, Localization, Aging and Sub-aging effects in trap models at very low temperature

We study in details the dynamics of the one dimensional symmetric trap model, via a real-space renormalization procedure which becomes exact in the limit of zero temperature. In this limit, the diffusion front in each sample consists in two delta peaks, which are completely out of equilibrium with each other. The statistics of the positions and weights of these delta peaks over the samples allows to obtain explicit results for all observables in the limit $T \to 0$. We first compute disorder averages of one-time observables, such as the diffusion front, the thermal width, the localization parameters, the two-particle correlation function, and the generating function of thermal cumulants of the position. We then study aging and sub-aging effects : our approach reproduces very simply the two different aging exponents and yields explicit forms for scaling functions of the various two-time correlations. We also extend the RSRG method to include systematic corrections to the previous zero temperature procedure via a series expansion in $T$. We then consider the generalized trap model with parameter $\alpha \in [0,1]$ and obtain that the large scale effective model at low temperature does not depend on $\alpha$ in any dimension, so that the only observables sensitive to $\alpha$ are those that measure the `local persistence', such as the probability to remain exactly in the same trap during a time interval. Finally, we extend our approach at a scaling level for the trap model in $d=2$ and obtain the two relevant time scales for aging properties.Comment: 33 pages, 3 eps figure

POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism

Objective: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome. Methods: Clinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome-wide sequencing were conducted. Results: Hallmarks of mitochondrial dysfunction were present in patients' tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970-1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells. Interpretation: This work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult-onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal-dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders

On the distribution of the Wigner time delay in one-dimensional disordered systems

We consider the scattering by a one-dimensional random potential and derive the probability distribution of the corresponding Wigner time delay. It is shown that the limiting distribution is the same for two different models and coincides with the one predicted by random matrix theory. It is also shown that the corresponding stochastic process is given by an exponential functional of the potential.Comment: 11 pages, four references adde

Continuous cerebroventricular administration of dopamine: A new treatment for severe dyskinesia in Parkinson’s disease?

In Parkinson’s disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7 days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30 days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia

Accelerating universe emergent from the landscape

We propose that the existence of the string landscape suggests the universe can be in a quantum glass state, where an extremely large viscosity is generated, and long distance dynamics slows down. At the same time, the short distance dynamics is not altered due to the separation of time scales. This scenario can help to understand some controversies in cosmology, for example the natural existence of slow roll inflation and dark energy in the landscape, the apparent smallness of the cosmological constant. We see also that moduli stabilization is no longer necessary. We further identify the glass transition point, where the viscosity diverges, as the location of the cosmic horizon. We try to reconstruct the geometry of the accelerating universe from the structure of the landscape, and find that the metric should have an infinite jump when crossing the horizon. We predict that the static coordinate metric for dS space breaks down outside the horizon.Comment: 20 pages, no figures, harvma

Accounting for risk of non linear portfolios: a novel Fourier approach

The presence of non linear instruments is responsible for the emergence of non Gaussian features in the price changes distribution of realistic portfolios, even for Normally distributed risk factors. This is especially true for the benchmark Delta Gamma Normal model, which in general exhibits exponentially damped power law tails. We show how the knowledge of the model characteristic function leads to Fourier representations for two standard risk measures, the Value at Risk and the Expected Shortfall, and for their sensitivities with respect to the model parameters. We detail the numerical implementation of our formulae and we emphasizes the reliability and efficiency of our results in comparison with Monte Carlo simulation.Comment: 10 pages, 12 figures. Final version accepted for publication on Eur. Phys. J.

Large Scale Cross-Correlations in Internet Traffic

The Internet is a complex network of interconnected routers and the existence of collective behavior such as congestion suggests that the correlations between different connections play a crucial role. It is thus critical to measure and quantify these correlations. We use methods of random matrix theory (RMT) to analyze the cross-correlation matrix C of information flow changes of 650 connections between 26 routers of the French scientific network `Renater'. We find that C has the universal properties of the Gaussian orthogonal ensemble of random matrices: The distribution of eigenvalues--up to a rescaling which exhibits a typical correlation time of the order 10 minutes--and the spacing distribution follow the predictions of RMT. There are some deviations for large eigenvalues which contain network-specific information and which identify genuine correlations between connections. The study of the most correlated connections reveals the existence of `active centers' which are exchanging information with a large number of routers thereby inducing correlations between the corresponding connections. These strong correlations could be a reason for the observed self-similarity in the WWW traffic.Comment: 7 pages, 6 figures, final versio