Genetic modifiers of cognitive maintenance among older adults.

ObjectiveIdentify genetic factors associated with cognitive maintenance in late life and assess their association with gray matter (GM) volume in brain networks affected in aging.MethodsWe conducted a genome-wide association study of ∼2.4 M markers to identify modifiers of cognitive trajectories in Caucasian participants (N = 7,328) from two population-based cohorts of non-demented elderly. Standardized measures of global cognitive function (z-scores) over 10 and 6 years were calculated among participants and mixed model regression was used to determine subject-specific cognitive slopes. "Cognitive maintenance" was defined as a change in slope of ≥ 0 and was compared with all cognitive decliners (slope < 0). In an independent cohort of cognitively normal older Caucasians adults (N = 122), top association findings were then used to create genetic scores to assess whether carrying more cognitive maintenance alleles was associated with greater GM volume in specific brain networks using voxel-based morphometry.ResultsThe most significant association was on chromosome 11 (rs7109806, P = 7.8 × 10(-8)) near RIC3. RIC3 modulates activity of α7 nicotinic acetylcholine receptors, which have been implicated in synaptic plasticity and beta-amyloid binding. In the neuroimaging cohort, carrying more cognitive maintenance alleles was associated with greater volume in the right executive control network (RECN; PFWE  = 0.01).ConclusionsThese findings suggest that there may be genetic loci that promote healthy cognitive aging and that they may do so by conferring robustness to GM in the RECN. Future work is required to validate top candidate genes such as RIC3 for involvement in cognitive maintenance

Use of a New Spirophosphine To Achieve Catalytic Enantioselective [4 + 1] Annulations of Amines with Allenes To Generate Dihydropyrroles

Due in part to the common occurrence of five-membered nitrogen heterocycles in bioactive molecules, the discovery of methods for the enantioselective synthesis of such structures is a useful endeavor. Building on a single example by Tong of a phosphine-catalyzed [4 + 1] annulation of an amine with an allene that furnished an achiral dihydropyrrole in 22% yield, we have developed, with the aid of a new chiral spirophosphine catalyst, a method with increased utility, specifically, improved yield, enhanced scope (the use of γ-substituted allenes), and good ee. The enantioenriched dihydropyrrole products can be transformed into other interesting families of compounds with very good stereoselectivity

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Precision timing of PSR J1012+5307 and strong-field GR tests

We report on the high precision timing analysis of the pulsar-white dwarf binary PSR J1012+5307. Using 15 years of multi-telescope data from the European Pulsar Timing Array (EPTA) network, a significant measurement of the variation of the orbital period is obtained. Using this ideal strong-field gravity laboratory we derive theory independent limits for both the dipole radiation and the variation of the gravitational constant.Comment: 3 pages, Proceedings of the 12th Marcel Grossmann Meeting on General Relativity (MG 12

Instantaneous interaction in massive gravity

In general relativity, the instantaneous contributions to the gravitational potentials cancel each other in observable, leaving the theory free of physical instantaneous interactions. In models where these subtle cancellations are spoiled by the presence of fields that break Lorentz invariance, physical instantaneous interactions are possible. Such interactions are studied for a model of Lorentz- violating massive gravity

Investigating Perceptual Congruence Between Data and Display Dimensions in Sonification

The relationships between sounds and their perceived meaning and connotations are complex, making auditory perception an important factor to consider when designing sonification systems. Listeners often have a mental model of how a data variable should sound during sonification and this model is not considered in most data:sound mappings. This can lead to mappings that are difficult to use and can cause confusion. To investigate this issue, we conducted a magnitude estimation experiment to map how roughness, noise and pitch relate to the perceived magnitude of stress, error and danger. These parameters were chosen due to previous findings which suggest perceptual congruency between these auditory sensations and conceptual variables. Results from this experiment show that polarity and scaling preference are dependent on the data:sound mapping. This work provides polarity and scaling values that may be directly utilised by sonification designers to improve auditory displays in areas such as accessible and mobile computing, process-monitoring and biofeedback

Static Ricci-flat 5-manifolds admitting the 2-sphere

We examine, in a purely geometrical way, static Ricci-flat 5-manifolds admitting the 2-sphere and an additional hypersurface-orthogonal Killing vector. These are widely studied in the literature, from different physical approaches, and known variously as the Kramer - Gross - Perry - Davidson - Owen solutions. The 2-fold infinity of cases that result are studied by way of new coordinates (which are in most cases global) and the cases likely to be of interest in any physical approach are distinguished on the basis of the nakedness and geometrical mass of their associated singularities. It is argued that the entire class of solutions has to be considered unstable about the exceptional solutions: the black string and soliton cases. Any physical theory which admits the non-exceptional solutions as the external vacuua of a collapsing object has to accept the possibility of collapse to zero volume leaving behind the weakest possible, albeit naked, geometrical singularities at the origin.Finally, it is pointed out that these types of solutions generalize, in a straightforward way, to higher dimensions.Comment: Generalize, in a straightforward way, to higher dimension

Phase space barriers and dividing surfaces in the absence of critical points of the potential energy: Application to roaming in ozone

We examine the phase space structures that govern reactiondynamics in the absence of critical points on the potential energy surface. We show that in the vicinity of hyperbolic invariant tori, it is possible to define phase space dividing surfaces that are analogous to the dividing surfaces governing transition from reactants to products near a critical point of the potential energy surface. We investigate the problem of capture of an atom by a diatomic molecule and show that a normally hyperbolic invariant manifold exists at large atom-diatom distances, away from any critical points on the potential. This normally hyperbolic invariant manifold is the anchor for the construction of a dividing surface in phase space, which defines the outer or loose transition state governing capture dynamics. We present an algorithm for sampling an approximate capture dividing surface, and apply our methods to the recombination of the ozone molecule. We treat both 2 and 3 degrees of freedom models with zero total angular momentum. We have located the normally hyperbolic invariant manifold from which the orbiting (outer) transition state is constructed. This forms the basis for our analysis of trajectories for ozone in general, but with particular emphasis on the roaming trajectories