Fluctuation theorems for harmonic oscillators

We study experimentally the thermal fluctuations of energy input and dissipation in a harmonic oscillator driven out of equilibrium, and search for Fluctuation Relations. We study transient evolution from the equilibrium state, together with non equilibrium steady states. Fluctuations Relations are obtained experimentally for both the work and the heat, for the stationary and transient evolutions. A Stationary State Fluctuation Theorem is verified for the two time prescriptions of the torque. But a Transient Fluctuation Theorem is satisfied for the work given to the system but not for the heat dissipated by the system in the case of linear forcing. Experimental observations on the statistical and dynamical properties of the fluctuation of the angle, we derive analytical expressions for the probability density function of the work and the heat. We obtain for the first time an analytic expression of the probability density function of the heat. Agreement between experiments and our modeling is excellent

La fauna asociada a Tubularia crocea (Agassiz, 1862) (anthomedusae; tubulariidae) y la aplicación de un método de cartificación

A systematic list of the organisms found on the polyps of T. crocea is presented. Monthly samples from the coast of Mar del Plata (38°03'S ; 57°31'W) allowed the analysis of the dynamic of the associations, specially with picnogonids, amphipods, annelids and nematodes, which varied in composition and abundance along of year. We present a modification of a mapping model of Marfenin (1980) and its use to present the different stages of the polyps and the localization of the associated organisms.Se presenta un listado sistemático de los organismos hallados sobre los pólipos de T. creocea. Muestras mensuales obtenidas en la costa de Mar del Plata (38°O8'S ; 57°31'W) permitieron el análisis de la dinámica de las asociaciones, especialmente con picnogónidos, anfípodos, anélidos y nemátodos, las cuales variaron en composición y abundancia a través del año. Nosotros presentamos una modificación del modelo de cartificación de Marfenin (1980) y su uso para representar distintos estados de los pólipos y la localización de los organismos asociados

Fluctuation relations and coarse-graining

We consider the application of fluctuation relations to the dynamics of coarse-grained systems, as might arise in a hypothetical experiment in which a system is monitored with a low-resolution measuring apparatus. We analyze a stochastic, Markovian jump process with a specific structure that lends itself naturally to coarse-graining. A perturbative analysis yields a reduced stochastic jump process that approximates the coarse-grained dynamics of the original system. This leads to a non-trivial fluctuation relation that is approximately satisfied by the coarse-grained dynamics. We illustrate our results by computing the large deviations of a particular stochastic jump process. Our results highlight the possibility that observed deviations from fluctuation relations might be due to the presence of unobserved degrees of freedom.Comment: 19 pages, 6 figures, very minor change

Replica analysis of the generalized p-spin interaction glass model

We investigate stability of replica symmetry breaking solutions in generalized $p$-spin models. It is shown that the kind of the transition to the one-step replica symmetry breaking state depends not only on the presence or absence of the reflection symmetry of the generalized "spin"-operators $\hat{U}$ but on the number of interacting operators and their individual characteristics.Comment: 14 pages, 1 figur

Analgesic Effect of a Mixed T-Type Channel Inhibitor/CB2 Receptor Agonist

Background: Cannabinoid receptors and T-type calcium channels are potential targets for treating pain. Here we report on the design, synthesis and analgesic properties of a new mixed cannabinoid/T-type channel ligand, NMP-181. Results: NMP-181 action on CB1 and CB2 receptors was characterized in radioligand binding and in vitro GTP gamma[S-35] functional assays, and block of transiently expressed human Cav3.2 T-type channels by NMP-181 was analyzed by patch clamp. The analgesic effects and in vivo mechanism of action of NMP-181 delivered spinally or systemically were analyzed in formalin and CFA mouse models of pain. NMP-181 inhibited peak Ca(V)3.2 currents with IC50 values in the low micromolar range and acted as a CB2 agonist. Inactivated state dependence further augmented the inhibitory action of NMP-181. NMP-181 produced a dose-dependent antinociceptive effect when administered either spinally or systemically in both phases of the formalin test. Both i.t. and i.p. treatment of mice with NMP-181 reversed the mechanical hyperalgesia induced by CFA injection. NMP-181 showed no antinocieptive effect in Ca(V)3.2 null mice. The antinociceptive effect of intrathecally delivered NMP-181 in the formalin test was reversed by i.t. treatment of mice with AM-630 (CB2 antagonist). In contrast, the NMP-181-induced antinociception was not affected by treatment of mice with AM-281 (CB1 antagonist). Conclusions: Our work shows that both T-type channels as well as CB2 receptors play a role in the antinociceptive action of NMP-181, and also provides a novel avenue for suppressing chronic pain through novel mixed T-type/cannabinoid receptor ligands

NMP-7 inhibits chronic inflammatory and neuropathic pain via block of Cab3.2 T-type calcium channels and activation of CB2 receptors

Background: T-type calcium channels and cannabinoid receptors are known to play important roles in chronic pain, making them attractive therapeutic targets. We recently reported on the design, synthesis and analgesic properties of a novel T-type channel inhibitor (NMP-7), which also shows mixed agonist activity on CB1 and CB2 receptors in vitro. Here, we analyzed the analgesic effect of systemically delivered NMP-7 (intraperitoneal (i.p.) or intragstric (i.g.) routes) on mechanical hypersensitivity in inflammatory pain induced by Complete Freund’s Adjuvant (CFA) and neuropathic pain induced by sciatic nerve injury. Results: NMP-7 delivered by either i.p. or i.g. routes produced dose-dependent inhibition of mechanical hyperalgesia in mouse models of inflammatory and neuropathic pain, without altering spontaneous locomotor activity in the open-field test at the highest active dose. Neither i.p. nor i.g. treatment reduced peripheral inflammation per se, as evaluated by examining paw edema and myeloperoxidase activity. The antinociception produced by NMP-7 in the CFA test was completely abolished in CaV3.2-null mice, confirming CaV3.2 as a key target. The analgesic action of intraperitoneally delivered NMP-7 was not affected by pretreatment of mice with the CB1 antagonist AM281, but was significantly attenuated by pretreatment with the CB2 antagonist AM630, suggesting that CB2 receptors, but not CB1 receptors are involved in the action of NMP-7 in vivo. Conclusions: Overall, our work shows that NMP-7 mediates a significant analgesic effect in a model of persistent inflammatory and chronic neuropathic pain by way of T-type channel modulation and CB2 receptor activation. Thus, this study provides a novel therapeutic avenue for managing chronic pain conditions via mixed CB ligands/ T-type channel blockers

Chaotic Hypothesis, Fluctuation Theorem and singularities

The chaotic hypothesis has several implications which have generated interest in the literature because of their generality and because a few exact predictions are among them. However its application to Physics problems requires attention and can lead to apparent inconsistencies. In particular there are several cases that have been considered in the literature in which singularities are built in the models: for instance when among the forces there are Lennard-Jones potentials (which are infinite in the origin) and the constraints imposed on the system do not forbid arbitrarily close approach to the singularity even though the average kinetic energy is bounded. The situation is well understood in certain special cases in which the system is subject to Gaussian noise; here the treatment of rather general singular systems is considered and the predictions of the chaotic hypothesis for such situations are derived. The main conclusion is that the chaotic hypothesis is perfectly adequate to describe the singular physical systems we consider, i.e. deterministic systems with thermostat forces acting according to Gauss' principle for the constraint of constant total kinetic energy (``isokinetic Gaussian thermostats''), close and far from equilibrium. Near equilibrium it even predicts a fluctuation relation which, in deterministic cases with more general thermostat forces (i.e. not necessarily of Gaussian isokinetic nature), extends recent relations obtained in situations in which the thermostatting forces satisfy Gauss' principle. This relation agrees, where expected, with the fluctuation theorem for perfectly chaotic systems. The results are compared with some recent works in the literature.Comment: 7 pages, 1 figure; updated to take into account comments received on the first versio

Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy

SummaryThe aim of this multicentric, retrospective, and uncontrolled study was to evaluate the efficacy and safety of levetiracetam (LEV) in 81 children younger than 4 years with refractory epilepsy. At an average follow-up period of 9 months, LEV administration was found to be effective in 30% of patients (responders showing more than a 50% decrease in seizure frequency) of whom 10 (12%) became seizure free. This efficacy was observed for focal (46%) as well as for generalized seizures (42%). In addition, in a group of 48 patients, we compared the initial efficacy (evaluated at an average of 3 months of follow-up) and the retention at a mean of 12 months of LEV, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-two patients (46%) were initial responders. After a minimum of 12 months of follow-up, 9 of 48 patients (19%) maintained the improvement, 4 (8%) of whom remained seizure free. A loss of efficacy was observed in 13 of the initial responders (59%). Maintained LEV efficacy was noted in patients with focal epilepsy and West syndrome. LEV was well tolerated. Adverse events were seen in 18 (34%) patients. The main side effects were drowsiness and nervousness. Adverse events were either tolerable or resolved in time with dosage reduction or discontinuation of the drug.We conclude that LEV is safe and effective for a wide range of epileptic seizures and epilepsy syndromes and, therefore, represents a valid therapeutic option in infants and young children affected by epilepsy

Tuning the Correlation Decay in the Resistance Fluctuations of Multi-Species Networks

A new network model is proposed to describe the $1/f^\alpha$ resistance noise in disordered materials for a wide range of $\alpha$ values ($0< \alpha < 2$). More precisely, we have considered the resistance fluctuations of a thin resistor with granular structure in different stationary states: from nearly equilibrium up to far from equilibrium conditions. This system has been modelled as a network made by different species of resistors, distinguished by their resistances, temperature coefficients and by the energies associated with thermally activated processes of breaking and recovery. The correlation behavior of the resistance fluctuations is analyzed as a function of the temperature and applied current, in both the frequency and time domains. For the noise frequency exponent, the model provides $0< \alpha < 1$ at low currents, in the Ohmic regime, with $\alpha$ decreasing inversely with the temperature, and $1< \alpha <2$ at high currents, in the non-Ohmic regime. Since the threshold current associated with the onset of nonlinearity also depends on the temperature, the proposed model qualitatively accounts for the complicate behavior of $\alpha$ versus temperature and current observed in many experiments. Correspondingly, in the time domain, the auto-correlation function of the resistance fluctuations displays a variety of behaviors which are tuned by the external conditions.Comment: 26 pages, 16 figures, Submitted to JSTAT - Special issue SigmaPhi200

Is it possible to experimentally verify the fluctuation relation? A review of theoretical motivations and numerical evidence

The theoretical motivations to perform experimental tests of the stationary state fluctuation relation are reviewed. The difficulties involved in such tests, evidenced by numerical simulations, are also discussed.Comment: 36 pages, 4 figures. Extended version of a presentation to the discussion "Is it possible to experimentally verify the fluctuation theorem?", IHP, Paris, December 1, 2006. Comments are very welcom