43 research outputs found
Applications of a New Proposal for Solving the "Problem of Time" to Some Simple Quantum Cosmological Models
We apply a recent proposal for defining states and observables in quantum
gravity to simple models. First, we consider a Klein-Gordon particle in an ex-
ternal potential in Minkowski space and compare our proposal to the theory ob-
tained by deparametrizing with respect to a time slicing prior to quantiza-
tion. We show explicitly that the dynamics of the deparametrization approach
depends on the time slicing. Our proposal yields a dynamics independent of the
choice of time slicing at intermediate times but after the potential is turned
off, the dynamics does not return to the free particle dynamics. Next we apply
our proposal to the closed Robertson-Walker quantum cosmology with a massless
scalar field with the size of the universe as our time variable, so the only
dynamical variable is the scalar field. We show that the resulting theory has
the semi-classical behavior up to the classical turning point from expansion to
contraction, i.e., given a classical solution which expands for much longer
than the Planck time, there is a quantum state whose dynamical evolution
closely approximates this classical solution during the expansion. However,
when the "time" gets larger than the classical maximum, the scalar field be-
comes "frozen" at its value at the maximum expansion. We also obtain similar
results in the Taub model. In an Appendix we derive the form of the Wheeler-
DeWitt equation for the Bianchi models by performing a proper quantum reduc-
tion of the momentum constraints; this equation differs from the usual one ob-
tained by solving the momentum constraints classically, prior to quantization.Comment: 30 pages, LaTeX 3 figures (postscript file or hard copy) available
upon request, BUTP-94/1
Generalized Quantum Theory of Recollapsing Homogeneous Cosmologies
A sum-over-histories generalized quantum theory is developed for homogeneous
minisuperspace type A Bianchi cosmological models, focussing on the particular
example of the classically recollapsing Bianchi IX universe. The decoherence
functional for such universes is exhibited. We show how the probabilities of
decoherent sets of alternative, coarse-grained histories of these model
universes can be calculated. We consider in particular the probabilities for
classical evolution defined by a suitable coarse-graining. For a restricted
class of initial conditions and coarse grainings we exhibit the approximate
decoherence of alternative histories in which the universe behaves classically
and those in which it does not. For these situations we show that the
probability is near unity for the universe to recontract classically if it
expands classically. We also determine the relative probabilities of
quasi-classical trajectories for initial states of WKB form, recovering for
such states a precise form of the familiar heuristic "J d\Sigma" rule of
quantum cosmology, as well as a generalization of this rule to generic initial
states.Comment: 41 pages, 4 eps figures, revtex 4. Modest revisions throughout.
Physics unchanged. To appear in Phys. Rev.
Whole-genome sequencing reveals host factors underlying critical COVID-19
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease