Wave Function of a Brane-like Universe

Within the mini-superspace model, brane-like cosmology means performing the variation with respect to the embedding (Minkowski) time $\tau$ before fixing the cosmic (Einstein) time $t$. The departure from Einstein limit is parameterized by the 'energy' conjugate to $\tau$, and characterized by a classically disconnected Embryonic epoch. In contrast with canonical quantum gravity, the wave-function of the brane-like Universe is (i) $\tau$-dependent, and (ii) vanishes at the Big Bang. Hartle-Hawking and Linde proposals dictate discrete 'energy' levels, whereas Vilenkin proposal resembles $\alpha$-particle disintegration.Comment: Revtex, 4 twocolumn pages, 3 eps figures (accepted for publication in Class. Quan. Grav.

Geodetic Brane Gravity

Within the framework of geodetic brane gravity, the Universe is described as a 4-dimensional extended object evolving geodetically in a higher dimensional flat background. In this paper, by introducing a new pair of canonical fields {lambda, P_{lambda}}, we derive the quadratic Hamiltonian for such a brane Universe; the inclusion of matter then resembles minimal coupling. Second class constraints enter the game, invoking the Dirac bracket formalism. The algebra of the first class constraints is calculated, and the BRST generator of the brane Universe turns out to be rank-1. At the quantum level, the road is open for canonical and/or functional integral quantization. The main advantages of geodetic brane gravity are: (i) It introduces an intrinsic, geometrically originated, 'dark matter' component, (ii) It offers, owing to the Lorentzian bulk time coordinate, a novel solution to the 'problem of time', and (iii) It enables calculation of meaningful probabilities within quantum cosmology without any auxiliary scalar field. Intriguingly, the general relativity limit is associated with lambda being a vanishing (degenerate) eigenvalue.Comment: 23 pages, 1 figure, minor change

Nucleation of (4)R^{(4)}R Brane Universes

The creation of brane universes induced by a totally antisymmetric tensor living in a fixed background spacetime is presented, where a term involving the intrinsic curvature of the brane is considered. A canonical quantum mechanical approach employing Wheeler-DeWitt equation is done. The probability nucleation for the brane is calculated taking into account both an instanton method and a WKB approximation. Some cosmological implications arose from the model are presented.Comment: 19 pages, 2 figure

An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p = 3.6×10−8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p = 2.6×10−13; SOX6, p = 6.4×10−10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation