Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects.

Activation of nicotinic acetylcholine receptors (nAChRs) is associated with the binding of agonists such as acetylcholine to an extracellular site that is located at the interface between two adjacent receptor subunits. More recently, there has been considerable interest in compounds, such as positive and negative allosteric modulators (PAMs and NAMs), that are able to modulate nAChR function by binding to distinct allosteric sites. Here we examined a series of compounds differing only in methyl substitution of a single aromatic ring. This series of compounds includes a previously described α7-selective allosteric agonist, cis-cis-4-p-tolyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4MP-TQS), together with all other possible combinations of methyl substitution at a phenyl ring (18 additional compounds). Studies conducted with this series of compounds have revealed five distinct pharmacological effects on α7 nAChRs. These five effects can be summarized as: 1) nondesensitizing activation (allosteric agonists), 2) potentiation associated with minimal effects on receptor desensitization (type I PAMs), 3) potentiation associated with reduced desensitization (type II PAMs), 4) noncompetitive antagonism (NAMs), and 5) compounds that have no effect on orthosteric agonist responses but block allosteric modulation (silent allosteric modulators (SAMs)). Several lines of experimental evidence are consistent with all of these compounds acting at a common, transmembrane allosteric site. Notably, all of these chemically similar compounds that have been classified as nondesensitizing allosteric agonists or as nondesensitizing (type II) PAMs are cis-cis-diastereoisomers, whereas all of the NAMs, SAMs, and type I PAMs are cis-trans-diastereoisomers. Our data illustrate the remarkable pharmacological diversity of allosteric modulators acting on nAChRs

Oxytocin and social pretreatment have similar effects on processing of negative emotional faces in healthy adult males

Oxytocin has been shown to affect several aspects of human social cognition, including facial emotion processing. There is also evidence that social stimuli (such as eye-contact) can effectively modulate endogenous oxytocin levels. In the present study we directly tested whether intranasal oxytocin administration and pre-treatment with social stimuli had similar effects on face processing at the behavioral level. Subjects (N = 52 healthy adult males) were presented with a set of faces with expressions of different valence (negative, neutral, positive) following different types of pretreatment (oxytocin—OT or placebo—PL and social interaction—Soc or no social interaction—NSoc, N = 13 in each) and were asked to rate all faces for perceived emotion and trustworthiness. On the next day subjects' recognition memory was tested on a set of neutral faces and additionally they had to again rate each face for trustworthiness and emotion. Subjects in both the OT and the Soc pretreatment group (as compared to the PL and to the NSoc groups) gave higher emotion and trustworthiness scores for faces with negative emotional expression. Moreover, 24 h later, subjects in the OT and Soc groups (unlike in control groups) gave lower trustworthiness scores for previously negative faces, than for faces previously seen as emotionally neutral or positive. In sum these results provide the first direct evidence of the similar effects of intranasal oxytocin administration and social stimulation on the perception of negative facial emotions as well as on the delayed recall of negative emotional information

Do Spatially Targeted Redevelopment Programs Spillover?

This paper estimates spillover effects from a spatially-targeted redevelopment program, the Federal Empowerment Zone (EZ), on neighboring and economically similar areas. EZs are a set of generous tax incentives and grants aimed at small, economically depressed areas of large U.S. cities. We find areas that border or are economically similar to EZ locations experience a decline in the number of establishments and employment compared to areas that border or are similar to rejected EZ applicants. We also demonstrate that using spillover prone areas to estimate program effects causes upward bias when the spillover is negative. We find that for many of our estimates, spillovers more than offset positive program effects, although there are instances when the net effect is small and positive

Volatility return intervals analysis of the Japanese market

We investigate scaling and memory effects in return intervals between price volatilities above a certain threshold $q$ for the Japanese stock market using daily and intraday data sets. We find that the distribution of return intervals can be approximated by a scaling function that depends only on the ratio between the return interval $\tau$ and its mean $$. We also find memory effects such that a large (or small) return interval follows a large (or small) interval by investigating the conditional distribution and mean return interval. The results are similar to previous studies of other markets and indicate that similar statistical features appear in different financial markets. We also compare our results between the period before and after the big crash at the end of 1989. We find that scaling and memory effects of the return intervals show similar features although the statistical properties of the returns are different.Comment: 11 page

Constant tension device for gravity simulation

Mechanical device for simulating lunar gravitation is described. Details of construction are illustrated and example of application is provided. Device works opposite to effects of earth gravity and produces effects similar to lunar conditions by providing mechanical lifting forces

MODERATE SEVERITY DISTURBANCE HAS SIMILAR EFFECTS ON THE PRODUCTION OF THREE FORESTS NESTED WITHIN THE UPPER GREAT LAKES LANDSCAPE

Moderate severity disturbances, which only kill a subset of canopy trees (e.g., via insects, pathogens, and windthrow), are increasingly widespread, and can alter forest structure and production. Whether moderate severity disturbance similarly affects the net primary production (NPP) of different forest stands within inherently heterogeneous landscapes, however, is unknown. We experimentally disturbed three, 2-ha stands varying in forest structure and primary production, reducing stand basal area 38 to 66 % by stem girdling all mature early successional aspen (Populus) and birch (Betula). For nearly a decade, we examined how the forest stands restructured and recovered, and linked post-recovery physical and biological structure with light absorption and wood NPP. Disturbance significantly altered the structure of all stands and prompted a similar decade-long pattern of primary production decline and recovery. All stands exhibited an initial reduction in wood NPP, recovering to, or exceeded pre-disturbance levels within eight years. Following the recovery of wood NPP, more biologically diverse forest canopies with higher leaf area indexes captured more light, and, subsequently, had higher rates of wood NPP. We provide limited support that disturbance may enhance long-term primary production through its effects on canopy structural reorganization. We conclude that, while the forests examined responded similarly to disturbance, improved understanding of different forest ecosystems’ response to disturbance remains critical to informing carbon management decisions across diverse landscape mosaics

Color Transparency at COMPASS energies

Pionic quasielastic knockout of protons from nuclei at 200 GeV show very large effects of color transparency as -t increases from 0 to several GeV^2. Similar effects are expected for quasielastic photoproduction of vector mesons.Comment: 9 pages, 4 figure

Evidence of aging in mean-field spin glass models

We study numerically the out of equilibrium dynamics of the hypercubic cell spin glass in high dimensionalities. We obtain evidence of aging effects qualitatively similar both to experiments and to simulations of low dimensional models. This suggests that the Sherrington-Kirkpatrick model as well as other mean-field finite connectivity lattices can be used to study these effects analytically.Comment: 13 pages + 5 figures (upon request

Quantum Dissipation and Decoherence via Interaction with Low-Dimensional Chaos: a Feynman-Vernon Approach

We study the effects of dissipation and decoherence induced on a harmonic oscillator by the coupling to a chaotic system with two degrees of freedom. Using the Feynman-Vernon approach and treating the chaotic system semiclassically we show that the effects of the low dimensional chaotic environment are in many ways similar to those produced by thermal baths. The classical correlation and response functions play important roles in both classical and quantum formulations. Our results are qualitatively similar to the high temperature regime of the Caldeira-Leggett model.Comment: 31 pages, 4 figure

Holographic Non-Fermi Liquid in a Background Magnetic Field

We study the effects of a non-zero magnetic field on a class of 2+1 dim non-Fermi liquids, recently found in 0903.2477 by considering properties of a fermionic probe in an extremal AdS^4 black hole background. Introducing a similar fermionic probe in a dyonic AdS^4 black hole geometry, we find that the effect of a magnetic field could be incorporated in a rescaling of the probe fermion's charge. From this simple fact, we observe interesting effects like gradual disappearance of the Fermi surface and quasi particle peaks at large magnetic fields and changes in other properties of the system. We also find Landau level like structures and oscillatory phenomena similar to the de Haas-van Alphen effect.Comment: 20 pages, latex, 6 figure