342 research outputs found
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 .
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 . We then consider the
generalized trap model with parameter and obtain that the
large scale effective model at low temperature does not depend on in
any dimension, so that the only observables sensitive to 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 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
- …