Gibbsian theory of power law distributions

It is shown that power law phase space distributions describe marginally stable Gibbsian equilibria far from thermal equilibrium which are expected to occur in collisionless plasmas containing fully developed quasi-stationary turbulence. Gibbsian theory is extended on the fundamental level to statistically dependent subsystems introducing an `ordering parameter' $\kappa$. Particular forms for the entropy and partition functions are derived with super-additive (non-extensive) entropy, and a redefinition of temperature in such systems is given.Comment: Physical Review Letters revised second revision (and shortened because of overlength) co-author adde

Generalised-Lorentzian Thermodynamics

We extend the recently developed non-gaussian thermodynamic formalism \cite{tre98} of a (presumably strongly turbulent) non-Markovian medium to its most general form that allows for the formulation of a consistent thermodynamic theory. All thermodynamic functions, including the definition of the temperature, are shown to be meaningful. The thermodynamic potential from which all relevant physical information in equilibrium can be extracted, is defined consistently. The most important findings are the following two: (1) The temperature is defined exactly in the same way as in classical statistical mechanics as the derivative of the energy with respect to the entropy at constant volume. (2) Observables are defined in the same way as in Boltzmannian statistics as the linear averages of the new equilibrium distribution function. This lets us conclude that the new state is a real thermodynamic equilibrium in systems capable of strong turbulence with the new distribution function replacing the Boltzmann distribution in such systems. We discuss the ideal gas, find the equation of state, and derive the specific heat and adiabatic exponent for such a gas. We also derive the new Gibbsian distribution of states. Finally we discuss the physical reasons for the development of such states and the observable properties of the new distribution function.Comment: 13 pages, 1 figur

Information Theory based on Non-additive Information Content

We generalize the Shannon's information theory in a nonadditive way by focusing on the source coding theorem. The nonadditive information content we adopted is consistent with the concept of the form invariance structure of the nonextensive entropy. Some general properties of the nonadditive information entropy are studied, in addition, the relation between the nonadditivity $q$ and the codeword length is pointed out.Comment: 9 pages, no figures, RevTex, accepted for publication in Phys. Rev. E(an error in proof of theorem 1 was corrected, typos corrected

Scaling exponent of the maximum growth probability in diffusion-limited aggregation

An early (and influential) scaling relation in the multifractal theory of Diffusion Limited Aggregation(DLA) is the Turkevich-Scher conjecture that relates the exponent \alpha_{min} that characterizes the ``hottest'' region of the harmonic measure and the fractal dimension D of the cluster, i.e. D=1+\alpha_{min}. Due to lack of accurate direct measurements of both D and \alpha_{min} this conjecture could never be put to serious test. Using the method of iterated conformal maps D was recently determined as D=1.713+-0.003. In this Letter we determine \alpha_{min} accurately, with the result \alpha_{min}=0.665+-0.004. We thus conclude that the Turkevich-Scher conjecture is incorrect for DLA.Comment: 4 pages, 5 figure

A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis

Maintaining the appropriate complement and content of lipids in cellular membranes is critical for normal neural function. Accumulating evidence suggests that even subtle perturbations in the lipid content of neurons and myelin can disrupt their function and may contribute to myelin and axonal degradation. In this study, we determined the composition and quantified the content of lipids and sterols in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) from control and multiple sclerosis brain tissues by electrospray ionization tandem mass spectrometry. Our results suggest that in active-multiple sclerosis, there is a shift in the lipid composition of NAWM and NAGM to a higher phospholipid and lower sphingolipid content. We found that this disturbance in lipid composition was reduced in NAGM but not in NAWM of inactive-multiple sclerosis. The pattern of disturbance in lipid composition suggests a metabolic defect that causes sphingolipids to be shuttled to phospholipid production. Modelling the biophysical consequence of this change in lipid composition of NAWM indicated an increase in the repulsive force between opposing bilayers that could explain decompaction and disruption of myelin structure

Sphingomimetic multiple sclerosis drug FTY720 activates vesicular synaptobrevin and augments neuroendocrine secretion

Neurotransmission and secretion of hormones involve a sequence of protein/lipid interactions with lipid turnover impacting on vesicle trafficking and ultimately fusion of secretory vesicles with the plasma membrane. We previously demonstrated that sphingosine, a sphingolipid metabolite, promotes formation of the SNARE complex required for membrane fusion and also increases the rate of exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and in hippocampal neurons. Recently a fungi-derived sphingosine homologue, FTY720, has been approved for treatment of multiple sclerosis. In its non-phosphorylated form FTY720 accumulates in the central nervous system, reaching high levels which could affect neuronal function. Considering close structural similarity of sphingosine and FTY720 we investigated whether FTY720 has an effect on regulated exocytosis. Our data demonstrate that FTY720 can activate vesicular synaptobrevin for SNARE complex formation and enhance exocytosis in neuroendocrine cells and neurons

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination

BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model