Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit

The ß subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE ß subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photoreceptors in the superior but not the inferior hemisphere of the retina were rescued. In the latter animals, intermediate stages of degeneration were observed in the transition zone between rescued and diseased photoreceptors. Pathologic changes in the retina ranged from vesiculation of the basalmost outer segment discs in otherwise structurally intact rod cells to photoreceptors with highly disorganized outer segments and intact inner segments. Totally or partially rescued retinas showed a corresponding restoration of cGMP PDE activity, whereas nonrescued retinas had minimal enzyme activity, characteristic of the rd phenotype. These transgenic animals provide models for studying the molecular basis of retinal degenerative disease and conclusively demonstrate that the phenotype of rd mice is produced by a defect in the ß subunit of cGMP PDE

Staying true with the help of others: doxastic self-control through interpersonal commitment

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective

AROUSING FEAR IN DENTAL HEALTH EDUCATION * , †

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65851/1/j.1752-7325.1965.tb00484.x.pd

Goal Difficulty and Openness to Interpersonal Goal Support

When people pursue important goals, they are often surrounded by close others who could provide help and support for the achievement of these goals. The present work investigated whether people are more likely to be open to such interpersonal goal support from a romantic partner when they perceive their goals as being easy versus difficult. Using a multiple methods approach, three studies revealed that, compared with the pursuit of easy goals, when people pursue difficult goals, they are less likely to seek out and be open to support from their romantic partner. Studies 2 and 3 revealed that the effect of goal difficulty on openness to support was partially mediated by loss in self-efficacy. Finally, Study 3 revealed that lack of openness to support can have detrimental long-term consequences for the relationship, as it undermines relationship well-being

Dynamic scaling regimes of collective decision making

We investigate a social system of agents faced with a binary choice. We assume there is a correct, or beneficial, outcome of this choice. Furthermore, we assume agents are influenced by others in making their decision, and that the agents can obtain information that may guide them towards making a correct decision. The dynamic model we propose is of nonequilibrium type, converging to a final decision. We run it on random graphs and scale-free networks. On random graphs, we find two distinct regions in terms of the "finalizing time" -- the time until all agents have finalized their decisions. On scale-free networks on the other hand, there does not seem to be any such distinct scaling regions

Zipf law in the popularity distribution of chess openings

We perform a quantitative analysis of extensive chess databases and show that the frequencies of opening moves are distributed according to a power-law with an exponent that increases linearly with the game depth, whereas the pooled distribution of all opening weights follows Zipf's law with universal exponent. We propose a simple stochastic process that is able to capture the observed playing statistics and show that the Zipf law arises from the self-similar nature of the game tree of chess. Thus, in the case of hierarchical fragmentation the scaling is truly universal and independent of a particular generating mechanism. Our findings are of relevance in general processes with composite decisions.Comment: 5 pages, 4 figure

Interior of a Schwarzschild black hole revisited

The Schwarzschild solution has played a fundamental conceptual role in general relativity, and beyond, for instance, regarding event horizons, spacetime singularities and aspects of quantum field theory in curved spacetimes. However, one still encounters the existence of misconceptions and a certain ambiguity inherent in the Schwarzschild solution in the literature. By taking into account the point of view of an observer in the interior of the event horizon, one verifies that new conceptual difficulties arise. In this work, besides providing a very brief pedagogical review, we further analyze the interior Schwarzschild black hole solution. Firstly, by deducing the interior metric by considering time-dependent metric coefficients, the interior region is analyzed without the prejudices inherited from the exterior geometry. We also pay close attention to several respective cosmological interpretations, and briefly address some of the difficulties associated to spacetime singularities. Secondly, we deduce the conserved quantities of null and timelike geodesics, and discuss several particular cases in some detail. Thirdly, we examine the Eddington-Finkelstein and Kruskal coordinates directly from the interior solution. In concluding, it is important to emphasize that the interior structure of realistic black holes has not been satisfactorily determined, and is still open to considerable debate.Comment: 15 pages, 7 figures, Revtex4. V2: Version to appear in Foundations of Physic

Exact solutions of Einstein and Einstein-scalar equations in 2 + 1 dimensions

A nonstatic and circularly symmetric exact solution of the Einstein equations (with a cosmological constant $\Lambda$ and null fluid) in $2+1$ dimensions is given. This is a nonstatic generalization of the uncharged spinless BTZ metric. For $\Lambda = 0$, the spacetime is though not flat, the Kretschmann invariant vanishes. The energy, momentum, and power output for this metric are obtained. Further a static and circularly symmetric exact solution of the Einstein-massless scalar equations is given, which has a curvature singularity at $r =0$ and the scalar field diverges at $r=0$ as well as at infinity .Comment: 8 pages, Latex, no numbe

Rhodopsin Expression Level Affects Rod Outer Segment Morphology and Photoresponse Kinetics

Background: The retinal rod outer segment is a sensory cilium that is specialized for the conversion of light into an electrical signal. Within the cilium, up to several thousand membranous disks contain as many as a billion copies of rhodopsin for efficient photon capture. Disks are continually turned over, requiring the daily synthesis of a prodigious amount of rhodopsin. To promote axial diffusion in the aqueous cytoplasm, the disks have one or more incisures. Across vertebrates, the range of disk diameters spans an order of magnitude, and the number and length of the incisures vary considerably, but the mechanisms controlling disk architecture are not well understood. The finding that transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure prompted us to test whether lowered rhodopsin levels constrain disk assembly. Methodology/Principal Findings: The structure and function of rods from hemizygous rhodopsin knockout (R+/−) mice with decreased rhodopsin expression were analyzed by transmission electron microscopy and single cell recording. R+/− rods were structurally altered in three ways: disk shape changed from circular to elliptical, disk surface area decreased, and the single incisure lengthened to divide the disk into two sections. Photocurrent responses to flashes recovered more rapidly than normal. A spatially resolved model of phototransduction indicated that changes in the packing densities of rhodopsin and other transduction proteins were responsible. The decrease in aqueous outer segment volume and the lengthened incisure had only minor effects on photon response amplitude and kinetics. Conclusions/Significance: Rhodopsin availability limits disk assembly and outer segment girth in normal rods. The incisure may buffer the supply of structural proteins needed to form larger disks. Decreased rhodopsin level accelerated photoresponse kinetics by increasing the rates of molecular collisions on the membrane. Faster responses, together with fewer rhodopsins, combine to lower overall sensitivity of R+/− rods to light