Estimating Lyapunov exponents in billiards

Dynamical billiards are paradigmatic examples of chaotic Hamiltonian dynamical systems with widespread applications in physics. We study how well their Lyapunov exponent, characterizing the chaotic dynamics, and its dependence on external parameters can be estimated from phase space volume arguments, with emphasis on billiards with mixed regular and chaotic phase spaces. We show that in the very diverse billiards considered here the leading contribution to the Lyapunov exponent is inversely proportional to the chaotic phase space volume, and subsequently discuss the generality of this relationship. We also extend the well established formalism by Dellago, Posch, and Hoover to calculate the Lyapunov exponents of billiards to include external magnetic fields and provide a software implementation of it

Distinctive Single-Channel Properties Of α4β2-Nicotinic Acetylcholine Receptor Isoforms

Central nervous system nicotinic acetylcholine receptors (nAChR) are predominantly of the α4β2 subtype. Two isoforms exist, with high or low agonist sensitivity (HS-(α4β2) 2 β2- and LS-(α4β2) 2 α4-nAChR). Both isoforms exhibit similar macroscopic potency and efficacy values at low acetylcholine (ACh) concentrations, mediated by a common pair of high-affinity α4(+)/(-)β2 subunit binding interfaces. However LS-(α4β2) 2 α4-nAChR also respond to higher concentrations of ACh, acting at a third α4(+)/(-)α4 subunit interface. To probe isoform functional differences further, HS- and LS-α4β2-nAChR were expressed in Xenopus laevis oocytes and single-channel responses were assessed using cell-attached patch-clamp. In the presence of a low ACh concentration, both isoforms produce low-bursting function. HS-(α4β2) 2 β2-nAChR exhibit a single conductance state, whereas LS-(α4β2) 2 α4-nAChR display two distinctive conductance states. A higher ACh concentration did not preferentially recruit either conductance state, but did result in increased LS-(α4β2) 2 α4-nAChR bursting and reduced closed times. Introduction of an α4(+)/(-)α4-interface loss-of-function α4W182A mutation abolished these changes, confirming this site’s role in mediating LS-(α4β2) 2 α4-nAChR responses. Small or large amplitude openings are highly-correlated within individual LS-(α4β2) 2 α4-nAChR bursts, suggesting that they arise from distinct intermediate states, each of which is stabilized by α4(+)/(-)α4 site ACh binding. These findings are consistent with α4(+)/(-)α4 subunit interface occupation resulting in allosteric potentiation of agonist actions at α4(+)/(-)β2 subunit interfaces, rather than independent induction of high conductance channel openings

Brain Phosphorus Magnetic Resonance Spectroscopy Imaging of Sleep Homeostasis and Restoration in Drug Dependence

Numerous reports have documented a high occurrence of sleep difficulties in drug-dependent populations, prompting researchers to characterize sleep profiles and physiology in drug abusing populations. This mini-review examines studies indicating that drug-dependent populations exhibit alterations in sleep homeostatic and restoration processes in response to sleep deprivation. Sleep deprivation is a principal sleep research tool that results in marked physiological challenge, which provides a means to examine sleep homeostatic processes in response to extended wakefulness. A report from our laboratory demonstrated that following recovery sleep from sleep deprivation, brain high-energy phosphates particularly beta–nucleoside triphosphate (beta-NTP) are markedly increased as measured with phosphorus magnetic resonance spectroscopy (MRS). A more recent study examined the effects of sleep deprivation in opiate-dependent methadone-maintained (MM) subjects. The study demonstrated increases in brain beta-NTP following recovery sleep. Interestingly, these increases were of a markedly greater magnitude in MM subjects compared to control subjects. A similar study examined sleep deprivation in cocaine-dependent subjects demonstrating that cocaine-dependent subjects exhibit greater increases in brain beta-NTP following recovery sleep when compared to control subjects. The studies suggest that sleep deprivation in both MM subjects and cocaine-dependent subjects is characterized by greater changes in brain ATP levels than control subjects. Greater enhancements in brain ATP following recovery sleep may reflect a greater disruption to or impact of sleep deprivation in drug dependent subjects, whereby sleep restoration processes may be unable to properly regulate brain ATP and maintain brain high-energy equilibrium. These studies support the notion of a greater susceptibility to sleep loss in drug dependent populations. Additional sleep studies in drug abusing populations are needed, particularly those that examine potential differential effects of sleep deprivation

Libertà ed equità nei processi di scelta. Il capability approach nell'orientamento

I processi di scelta che indirizzano la vita di un individuo, quelli che orientano i suoi percorsi formativi e professionali, determinano la qualità del suo benessere personale, del suo star bene esistenziale. Il raggiungimento e il perseguimento di questo star bene, e la valorizzazione della qualità della vita per lo sviluppo umano, sono al centro delle riflessioni del capability approach di Amartya Sen. Nell'articolo si presentano i concetti fondamentali per i processi di scelta: - Functionings come stati “di essere e di fare” (being e doing) costitutivi dell'esistenza personale; - Capability come libertà / opportunità di una persona di acquisire i funzionamenti che reputa rilevanti per la propria esistenza; - Well-being (star-bene) come benessere soggettivo dato dai funzionamenti acquisiti; - Agency (agentività) come possibilità e abilità d’azione della persona nel voler raggiungere qualunque cosa essa decida, in quanto agente responsabile

β-Amyloid Directly Inhibits Human α4β3-Nicotinic Acetylcholine Receptors Heterologously Expressed In Human Sh-Ep1 Cells

Amyloid-β (Aβ) accumulation and aggregation are thought to contribute to the pathogenesis of Alzheimer\u27s disease (AD). In AD, there is a selective decrease in the numbers of radioligand binding sites corresponding to the most abundant nicotinic acetylcholine receptor (nAChR) subtype, which contains human α4 and β2 subunits (hα4β2-nAChR). However, the relationships between these phenomena are uncertain, and effects of Aβ on hα4β2-nAChR function have not been investigated in detail. We first confirmed expression of hα4 and hβ2 subunits as messenger RNA in transfected, human SH-EP1 cells by reverse transcription-polymerase chain reaction and mRNA fluorescence in situ, hybridization analyses. Immunoprecipitation Western analyses confirmed α4 and β2 subunit protein expression and coassembly. Whole cell current recording demonstrated heterologous expression in SH-EP1-hα4β2 cells of functional hα4β2-nAChRs with characteristic responses to nicotinic agonists or antagonists. Nicotine-induced whole cell currents were suppressed by Aβ1-42 in a dose-dependent manner. Functional inhibition was selective for Aβ1-42compared with the functionally inactive, control peptide Aβ40-1. Aβ1-42-mediated inhibition of hα4β2-nAChR function was non-competitive, voltage-independent, and use-independent. Pre-loading of cells with guanyl-5′-yl thiophosphate failed to prevent Aβ1-42- induced inhibition, suggesting that down-regulation of hα4β2-nAChR function by Aβ1-42 is not mediated by nAChR intemalization. Sensitivity to Aβj_42 antagonism at 1 nM was evident for hα4β2-nAChRs, but not for heterologously expressed human α7-nAChRs, although both nAChR subtypes were functionally inhibited by 100 nM Aβ1-42, with the magnitude of functional block being higher for 100 nM Aβ1-42 acting on hα7-nAChRs. These findings suggest that hα4β2-nAChRs are sensitive and perhaps pathophysiologically relevant targets for Aβ neurotoxicity in AD

Function Of Human α3β4α5 Nicotinic Acetylcholine Receptors Is Reduced By The β5(D398N) Variant

Genome-wide studies have strongly associated a non-synonymous polymorphism (rs16969968) that changes the 398th amino acid in the nAChR α5 subunit from aspartic acid to asparagine (D398N), with greater risk for increased nicotine consumption. We have used a pentameric concatemer approach to express defined and consistent populations of α3β4α5 nAChR in Xenopus oocytes. α5(Asn-398; risk) variant incorporation reduces ACh-evoked function compared with inclusion of the common α5(Asp-398) variant without altering agonist or antagonist potencies. Unlinked α3, β4, and α5 subunits assemble to form a uniform nAChR population with pharmacological properties matching those of concatemeric α3β4* nAChRs. α5 subunit incorporation reduces α3β4* nAChR function after coinjection with unlinked α3 and β4 subunits but increases that of α3β4α5 versus α3β4-only concatemers. α5 subunit incorporation into α3β4* nAChR also alters the relative efficacies of competitive agonists and changes the potency of the non-competitive antagonist mecamylamine. Additional observations indicated that in the absence of α5 subunits, free α3 and β4 subunits form at least two further subtypes. The pharmacological profiles of these free subunit α3β4-only subtypes are dissimilar both to each other and to those of α3β4α5 nAChR. The α5 variant-induced change in α3β4α5 nAChR function may underlie some of the phenotypic changes associated with this polymorphism. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

The effect of the phenylene linkage in poly(fluorene-alt-phenylene)s on the thermodynamics and kinetics of nitroaromatic and nitroaliphatic sensing

The preparation, photophysical characterization and sensing of a series of highly luminescent poly(fluorene-alt-phenylene)s (PFP) were studied. These PFP polymers varied the phenylene linkage in the 1,4 (PFP-p), 1,3 (PFP-m) and 1,2 (PFP-o) positions. The photoluminescence of these polymers ranged from ultraviolet to blue in color in both solution and film states by simply varying the linkage of the phenylene moiety. Photon Electron Spectroscopy in Air (PESA) revealed that the change in the emission was primarily attributed to the difference of the electron affinity of the polymer. Stern-Volmer quenching studies indicated that these poly(fluorene-alt-phenylene) polymers are highly sensitive towards nitroaromatic materials in solution, particularly in comparison to the reference poly(9,9-di-n-hexylflourene) (PDHF). These PFP polymers were found to be four to ten times more sensitive towards dinitrobenzene as compared to PDHF. In addition, PFP-o displayed the highest polymer-based Stern-Volmer quenching towards the taggant DMNB. The solid-state fluorescence quenching of the PFP-p and PFP-m films using DMNB was enhanced (up to 71.5%) compared to the reference PDHF (59.6%) and was attributed to both thermodynamic and diffusion kinetic factors