York Friends 1939-1945

This article deals with the experiences of York Quakers during the Second World War (1939-1945). It points out that in York as elsewhere Quakers had to make difficult choices during these years and tries to explain the reasons for these choices, particularly whether to support the war and, in many cases, whether to serve in the armed forces. The choices made by individuals and the consequences are elaborated. The article sets developments in York against the national background and points out that the national Quaker yearly meeting was held in York in 1941 and 1942

Dysfunctional Light-Evoked Regulation of cAMP in Photoreceptors and Abnormal Retinal Adaptation in Mice Lacking Dopamine D4 Receptors

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/ D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photoreceptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist L-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.Fil: Nir, Izhak. The University of Texas Health Science Center; Estados UnidosFil: Harrison, Joseph M.. The University of Texas Health Science Center; Estados UnidosFil: Haque, Rashidul. Emory University School of Medicine; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Grandy, David K.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Iuvone, P. Michael. Emory University School of Medicine; Estados Unido

Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.Fil: Thanos, P. K.. NIAAA Intramural Program; Estados Unidos. Brookhaven National Laboratory; Estados Unidos. Universidad de Buenos Aires; ArgentinaFil: Bermeo, C.. Brookhaven National Laboratory; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires; ArgentinaFil: Suchland, K. L.. Oregon Health & Science University; Estados UnidosFil: Wang, G. J.. Brookhaven National Laboratory; Estados UnidosFil: Grandy, David K.. Oregon Health & Science University; Estados UnidosFil: Volkow, N. D.. NIAAA Intramural Program; Estados Unido

Sweepouts of amalgamated 3-manifolds

We show that if two 3-manifolds with toroidal boundary are glued via a `sufficiently complicated' map then every Heegaard splitting of the resulting 3-manifold is weakly reducible. Additionally, if Z is a manifold obtained by gluing X and Y, two connected small manifolds with incompressible boundary, along a closed surface F. Then the genus g(Z) of Z is greater than or equal to 1/2(g(X)+g(Y)-2g(F)). Both results follow from a new technique to simplify the intersection between an incompressible surface and a strongly irreducible Heegaard splitting.Comment: This is the version published by Algebraic & Geometric Topology on 24 February 200

On the Propagation of Slip Fronts at Frictional Interfaces

The dynamic initiation of sliding at planar interfaces between deformable and rigid solids is studied with particular focus on the speed of the slip front. Recent experimental results showed a close relation between this speed and the local ratio of shear to normal stress measured before slip occurs (static stress ratio). Using a two-dimensional finite element model, we demonstrate, however, that fronts propagating in different directions do not have the same dynamics under similar stress conditions. A lack of correlation is also observed between accelerating and decelerating slip fronts. These effects cannot be entirely associated with static local stresses but call for a dynamic description. Considering a dynamic stress ratio (measured in front of the slip tip) instead of a static one reduces the above-mentioned inconsistencies. However, the effects of the direction and acceleration are still present. To overcome this we propose an energetic criterion that uniquely associates, independently on the direction of propagation and its acceleration, the slip front velocity with the relative rise of the energy density at the slip tip.Comment: 15 pages, 6 figure

Skating on a Film of Air: Drops Impacting on a Surface

Drops impacting on a surface are ubiquitous in our everyday experience. This impact is understood within a commonly accepted hydrodynamic picture: it is initiated by a rapid shock and a subsequent ejection of a sheet leading to beautiful splashing patterns. However, this picture ignores the essential role of the air that is trapped between the impacting drop and the surface. Here we describe a new imaging modality that is sensitive to the behavior right at the surface. We show that a very thin film of air, only a few tens of nanometers thick, remains trapped between the falling drop and the surface as the drop spreads. The thin film of air serves to lubricate the drop enabling the fluid to skate on the air film laterally outward at surprisingly high velocities, consistent with theoretical predictions. Eventually this thin film of air must break down as the fluid wets the surface. We suggest that this occurs in a spinodal-like fashion, and causes a very rapid spreading of a wetting front outwards; simultaneously the wetting fluid spreads inward much more slowly, trapping a bubble of air within the drop. Our results show that the dynamics of impacting drops are much more complex than previously thought and exhibit a rich array of unexpected phenomena that require rethinking classical paradigms.Comment: 4 pages, 4 figure

Failure of Intravenous Morphine to Serve as an Effective Instrumental Reinforcer in Dopamine D2 Receptor Knock-Out Mice

The rewarding effects of opiates are thought to be mediated through dopaminergic mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the nucleus accumbens, or both. The purpose of the present study was to explore the contribution of dopamine to opiate-reinforced behavior using D2 receptor knock-out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to lever press for water reinforcement and then implanted with intravenous catheters. The ability of intravenously delivered morphine to maintain lever pressing in these mice was studied under two schedules of reinforcement: a fixed ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and heterozygous mice, FR4 behavior maintained by morphine injections was significantly greater than behavior maintained by vehicle injections. Response rate was inversely related to injection dose and increased significantly in the wild-type and heterozygous mice when the animals were placed on the PR schedule. In contrast, the knock-out mice did not respond more for morphine than for saline and did not respond more when increased ratios were required by the PR schedule. Thus, morphine served as a positive reinforcer in the wild-type and heterozygous mice but failed to do so in the knock-out mice. Under this range of doses and response requirements, the rewarding effects of morphine appear to depend critically on an intact D2 receptor systemFil: Elmer, Greg I.. University of Maryland; Estados UnidosFil: Pieper, Jeanne O.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Low, Malcolm J.. Oregon Health and Sciences University; Estados UnidosFil: Grandy, David K.. Oregon Health and Sciences University; Estados UnidosFil: Wise, Roy A.. National Institutes of Health; Estados Unido