Discrete quantum gravity in the framework of Regge calculus formalism

An approach to the discrete quantum gravity based on the Regge calculus is discussed which was developed in a number of our papers. Regge calculus is general relativity for the subclass of general Riemannian manifolds called piecewise flat ones. Regge calculus deals with the discrete set of variables, triangulation lengths, and contains continuous general relativity as a particular limiting case when the lengths tend to zero. In our approach the quantum length expectations are nonzero and of the order of Plank scale $10^{-33}cm$. This means the discrete spacetime structure on these scales.Comment: LaTeX, 16 pages, to appear in JET

Regge calculus in the canonical form

(3+1) (continuous time) Regge calculus is reduced to Hamiltonian form. The constraints are classified, classical and quantum consequences are discussed. As basic variables connection matrices and antisymmetric area tensors are used supplemented with appropriate bilinear constraints. In these variables the action can be made quasipolinomial with $\arcsin$ as the only deviation from polinomiality. In comparison with analogous formalism in the continuum theory classification of constraints changes: some of them disappear, the part of I class constraints including Hamiltonian one become II class (and vice versa, some new constraints arise and some II class constraints become I class). As a result, the number of the degrees of freedom coincides with the number of links in 3-dimensional leaf of foliation. Moreover, in empty space classical dynamics is trivial: the scale of timelike links become zero and spacelike links are constant.Comment: 24 pages,Plain LaTeX,BINP 93-4

A fully (3+1)-D Regge calculus model of the Kasner cosmology

We describe the first discrete-time 4-dimensional numerical application of Regge calculus. The spacetime is represented as a complex of 4-dimensional simplices, and the geometry interior to each 4-simplex is flat Minkowski spacetime. This simplicial spacetime is constructed so as to be foliated with a one parameter family of spacelike hypersurfaces built of tetrahedra. We implement a novel two-surface initial-data prescription for Regge calculus, and provide the first fully 4-dimensional application of an implicit decoupled evolution scheme (the ``Sorkin evolution scheme''). We benchmark this code on the Kasner cosmology --- a cosmology which embodies generic features of the collapse of many cosmological models. We (1) reproduce the continuum solution with a fractional error in the 3-volume of 10^{-5} after 10000 evolution steps, (2) demonstrate stable evolution, (3) preserve the standard deviation of spatial homogeneity to less than 10^{-10} and (4) explicitly display the existence of diffeomorphism freedom in Regge calculus. We also present the second-order convergence properties of the solution to the continuum.Comment: 22 pages, 5 eps figures, LaTeX. Updated and expanded versio

From covariant to canonical formulations of discrete gravity

Starting from an action for discretized gravity we derive a canonical formalism that exactly reproduces the dynamics and (broken) symmetries of the covariant formalism. For linearized Regge calculus on a flat background -- which exhibits exact gauge symmetries -- we derive local and first class constraints for arbitrary triangulated Cauchy surfaces. These constraints have a clear geometric interpretation and are a first step towards obtaining anomaly--free constraint algebras for canonical lattice gravity. Taking higher order dynamics into account the symmetries of the action are broken. This results in consistency conditions on the background gauge parameters arising from the lowest non--linear equations of motion. In the canonical framework the constraints to quadratic order turn out to depend on the background gauge parameters and are therefore pseudo constraints. These considerations are important for connecting path integral and canonical quantizations of gravity, in particular if one attempts a perturbative expansion.Comment: 37 pages, 5 figures (minor modifications, matches published version + updated references

Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased" agonists on VDR and inverse agonists on RORα and RORγ

The classical pathway of vitamin D activation follows the sequence D3→25(OH)D3→1,25(OH)(2)D3 with the final product acting on the receptor for vitamin D (VDR). An alternative pathway can be started by the action of CYP11A1 on the side chain of D3, primarily producing 20(OH)D3, 22(OH)D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3 and 17,20,23(OH)(3)D3. Some of these metabolites are hydroxylated by CYP27B1 at C1α, by CYP24A1 at C24 and C25, and by CYP27A1 at C25 and C26. The products of these pathways are biologically active. In the epidermis and/or serum or adrenals we detected 20(OH)D3, 22(OH)D3, 20,22(OH)(2)D3, 20,23(OH)(2)D3, 17,20,23(OH)(3)D3, 1,20(OH)(2)D3, 1,20,23(OH)(3)D3, 1,20,22(OH)(3)D3, 20,24(OH)(2)D3, 1,20,24(OH)(3)D3, 20,25(OH)(2)D3, 1,20,25(OH)(3)D3, 20,26(OH)(2)D3 and 1,20,26(OH)(3)D3. 20(OH)D3 and 20,23(OH)(2)D3 are non-calcemic, while the addition of an OH at C1α confers some calcemic activity. Molecular modeling and functional assays show that the major products of the pathway can act as “biased” agonists for the VDR with high docking scores to the ligand binding domain (LBD), but lower than that of 1,25(OH)(2)D3. Importantly, cell based functional receptor studies and molecular modeling have identified the novel secosteroids as inverse agonists of both RORα and RORγ receptors. Specifically, they have high docking scores using crystal structures of RORα and RORγ LBDs. Furthermore, 20(OH)D3 and 20,23(OH)(2)D3 have been tested in cell model that expresses a Tet-on RORα or RORγ vector and a RORE-LUC reporter (ROR-responsive element), and in a mammalian 2-hybrid model that test interactions between an LBD-interacting LXXLL-peptide and the LBD of RORα/γ. These assays demonstrated that the novel secosteroids have ROR-antagonist activities that were further confirmed by the inhibition of IL17 promoter activity in cells overexpressing RORα/γ. In conclusion, endogenously produced novel D3 hydroxy-derivatives can act both as “biased” agonists of the VDR and/or inverse agonists of RORα/γ. We suggest that the identification of large number of endogenously produced alternative hydroxy-metabolites of D3 that are biologically active, and of possible alternative receptors, may offer an explanation for the pleiotropic and diverse activities of vitamin D, previously assigned solely to 1,25(OH)(2)D3 and VDR

Characterization of a new pathway that activates lumisterol <i>in vivo</i> to biologically active hydroxylumisterols

Abstract Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others including RORA and RORC. Molecular modeling and studies on VDRE-transcriptional activity excludes action through the genomic site of the VDR. However, their favorable interactions with the A-pocket in conjunction with VDR translocation studies suggest they may act on this non-genomic VDR site. Inhibition of RORα and RORγ transactivation activities in a Tet-on CHO cell reporter system, RORα co-activator assays and inhibition of (RORE)-LUC reporter activity in skin cells, in conjunction with molecular modeling, identified RORα and RORγ as excellent receptor candidates for the hydroxylumisterols. Thus, we have discovered a new biologically relevant, lumisterogenic pathway, the metabolites of which display biological activity. This opens a new area of endocrine research on the effects of the hydroxylumisterols on different pathways in different cells and the mechanisms involved

Effect of telehealth on glycaemic control: analysis of patients with type 2 diabetes in the Whole Systems Demonstrator cluster randomised trial

Background: The Whole Systems Demonstrator was a large, pragmatic, cluster randomised trial that compared telehealth with usual care among 3,230 patients with long-term conditions in three areas of England. Telehealth involved the regular transmission of physiological information such as blood glucose to health professionals working remotely. We examined whether telehealth led to changes in glycosylated haemoglobin (HbA1c) among the subset of patients with type 2 diabetes. Methods: The general practice electronic medical record was used as the source of information on HbA1c. Effects on HbA1c were assessed using a repeated measures model that included all HbA1c readings recorded during the 12-month trial period, and adjusted for differences in HbA1c readings recorded before recruitment. Secondary analysis averaged multiple HbA1c readings recorded for each individual during the trial period. Results: 513 of the 3,230 participants were identified as having type 2 diabetes and thus were included in the study. Telehealth was associated with lower HbA1c than usual care during the trial period (difference 0.21% or 2.3 mmol/mol, 95% CI, 0.04% to 0.38%, p = 0.013). Among the 457 patients in the secondary analysis, mean HbA1c showed little change for controls following recruitment, but fell for intervention patients from 8.38% to 8.15% (68 to 66 mmol/mol). A higher proportion of intervention patients than controls had HbA1c below the 7.5% (58 mmol/mol) threshold that was targeted by general practices (30.4% vs. 38.0%). This difference, however, did not quite reach statistical significance (adjusted odds ratio 1.63, 95% CI, 0.99 to 2.68, p = 0.053). Conclusions: Telehealth modestly improved glycaemic control in patients with type 2 diabetes over 12 months. The scale of the improvements is consistent with previous meta-analyses, but was relatively modest and seems unlikely to produce significant patient benefit

Discrete approaches to quantum gravity in four dimensions

The construction of a consistent theory of quantum gravity is a problem in theoretical physics that has so far defied all attempts at resolution. One ansatz to try to obtain a non-trivial quantum theory proceeds via a discretization of space-time and the Einstein action. I review here three major areas of research: gauge-theoretic approaches, both in a path-integral and a Hamiltonian formulation, quantum Regge calculus, and the method of dynamical triangulations, confining attention to work that is strictly four-dimensional, strictly discrete, and strictly quantum in nature.Comment: 33 pages, invited contribution to Living Reviews in Relativity; the author welcomes any comments and suggestion

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies