The cosmic gravitational wave background in a cyclic universe

Inflation predicts a primordial gravitational wave spectrum that is slightly ``red,'' i.e., nearly scale-invariant with slowly increasing power at longer wavelengths. In this paper, we compute both the amplitude and spectral form of the primordial tensor spectrum predicted by cyclic/ekpyrotic models. The spectrum is blue and exponentially suppressed compared to inflation on long wavelengths. The strongest observational constraint emerges from the requirement that the energy density in gravitational waves should not exceed around 10 per cent of the energy density at the time of nucleosynthesis.Comment: 4 pages, 3 figuer

Quantum Fields in a Big Crunch/Big Bang Spacetime

We consider quantum field theory on a spacetime representing the Big Crunch/Big Bang transition postulated in the ekpyrotic or cyclic cosmologies. We show via several independent methods that an essentially unique matching rule holds connecting the incoming state, in which a single extra dimension shrinks to zero, to the outgoing state in which it re-expands at the same rate. For free fields in our construction there is no particle production from the incoming adiabatic vacuum. When interactions are included the total particle production for fixed external momentum is finite at tree level. We discuss a formal correspondence between our construction and quantum field theory on de Sitter spacetime.Comment: 30 pages, RevTex file, five postscript figure file

Cosmological Perturbations in a Big Crunch/Big Bang Space-time

A prescription is developed for matching general relativistic perturbations across singularities of the type encountered in the ekpyrotic and cyclic scenarios i.e. a collision between orbifold planes. We show that there exists a gauge in which the evolution of perturbations is locally identical to that in a model space-time (compactified Milne mod Z_2) where the matching of modes across the singularity can be treated using a prescription previously introduced by two of us. Using this approach, we show that long wavelength, scale-invariant, growing-mode perturbations in the incoming state pass through the collision and become scale-invariant growing-mode perturbations in the expanding hot big bang phase.Comment: 47 pages, 4 figure

Conditions for Generating Scale-Invariant Density Perturbations

We analyze the general conditions on the equation of state $w$ required for quantum fluctuations of a scalar field to produce a scale-invariant spectrum of density perturbations, including models which (in the four dimensional effective description) bounce from a contracting to an expanding phase. We show that there are only two robust cases: $w\approx -1$ (inflation) and $w \gg 1$ (the ekpyrotic/cyclic scenario). All other cases, including the $w \approx 0$ case considered by some authors, require extreme fine-tuning of initial conditions and/or the effective potential. For the ekpyrotic/cyclic ($w \gg 1$) case, we also analyze the small deviations from scale invariance.Comment: 6 pages, no figure

Long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: a modelling study

BACKGROUND: Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity.METHODS AND FINDINGS: We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus.CONCLUSIONS: Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.</p

Cosmological Perturbations Through a General Relativistic Bounce

The ekpyrotic and cyclic universe scenarios have revived the idea that the density perturbations apparent in today's universe could have been generated in a `pre-singularity' epoch before the big bang. These scenarios provide explicit mechanisms whereby a scale invariant spectrum of adiabatic perturbations may be generated without the need for cosmic inflation, albeit in a phase preceding the hot big bang singularity. A key question they face is whether there exists a unique prescription for following perturbations through the bounce, an issue which is not yet definitively settled. This goal of this paper is more modest, namely to study a bouncing Universe model in which neither General Relativity nor the Weak Energy Condition is violated. We show that a perturbation which is pure growing mode before the bounce does not match to a pure decaying mode perturbation after the bounce. Analytical estimates of when the comoving curvature perturbation varies around the bounce are given. It is found that in general it is necessary to evaluate the evolution of the perturbation through the bounce in detail rather than using matching conditions.Comment: 15 pages, 6 figures. Added more details showing how and when the comoving curvature perturbation varies on large scales during the bounc

The Ekpyrotic Universe: Colliding Branes and the Origin of the Hot Big Bang

We propose a cosmological scenario in which the hot big bang universe is produced by the collision of a brane in the bulk space with a bounding orbifold plane, beginning from an otherwise cold, vacuous, static universe. The model addresses the cosmological horizon, flatness and monopole problems and generates a nearly scale-invariant spectrum of density perturbations without invoking superluminal expansion (inflation). The scenario relies, instead, on physical phenomena that arise naturally in theories based on extra dimensions and branes. As an example, we present our scenario predominantly within the context of heterotic M-theory. A prediction that distinguishes this scenario from standard inflationary cosmology is a strongly blue gravitational wave spectrum, which has consequences for microwave background polarization experiments and gravitational wave detectors.Comment: 67 pages, 4 figures. v2,v3: minor corrections, references adde

Cosmological parameters from CMB and other data: a Monte-Carlo approach

We present a fast Markov Chain Monte-Carlo exploration of cosmological parameter space. We perform a joint analysis of results from recent CMB experiments and provide parameter constraints, including sigma_8, from the CMB independent of other data. We next combine data from the CMB, HST Key Project, 2dF galaxy redshift survey, supernovae Ia and big-bang nucleosynthesis. The Monte Carlo method allows the rapid investigation of a large number of parameters, and we present results from 6 and 9 parameter analyses of flat models, and an 11 parameter analysis of non-flat models. Our results include constraints on the neutrino mass (m_nu < 0.3eV), equation of state of the dark energy, and the tensor amplitude, as well as demonstrating the effect of additional parameters on the base parameter constraints. In a series of appendices we describe the many uses of importance sampling, including computing results from new data and accuracy correction of results generated from an approximate method. We also discuss the different ways of converting parameter samples to parameter constraints, the effect of the prior, assess the goodness of fit and consistency, and describe the use of analytic marginalization over normalization parameters.Comment: Quintessence results now include perturbations. Changes to match version accepted by PRD. MCMC code and data are available at http://cosmologist.info/cosmomc/ along with a B&W printer-friendly version of the pape

HIV-1 Vpu Protein Mediates the Transport of Potassium in Saccharomyces cerevisiae

Human immunodeficiency virus type 1 (HIV-1) Vpu is an integral membrane protein that belongs to the viroporin family. Viroporins interact with cell membranes, triggering membrane permeabilization and promoting release of viral particles. In vitro electrophysiological methods have revealed changes in membrane ion currents when Vpu is present; however, in vivo the molecular mechanism of Vpu at the plasma membrane is still uncertain. We used the yeast Saccharomyces cerevisiae as a genetic model system to analyze how Vpu ion channel impacts cellular homeostasis. Inducible expression of Vpu impaired cell growth, suggesting that this viral protein is toxic to yeast cultures. This toxicity decreased with extracellular acidic pH. Also, Vpu toxicity diminished as the extracellular K(+) concentration was increased. However, expression of the Vpu protein suppresses the growth defect of K(+) uptake-deficient yeast (Δtrk1,2). The phenotype rescue of these highly hyperpolarized cells was almost total when they were grown in medium supplemented with high concentrations of KCl (100 mM) at pH 7.0 but was significantly reduced when the extracellular K(+) concentration or pH was decreased. These results indicate that Vpu has the ability to modify K(+) transport in both yeast strains. Here, we show also that Vpu confers tolerance to the aminoglycoside antibiotic hygromycin B in Δtrk1,2 yeast. Our results suggest that Vpu interferes with cell growth of wild-type yeast but improves proliferation of the hyperpolarized trk1,2 mutant by inducing plasma membrane depolarization. Furthermore, evaluation of the ion channel activity of the Vpu protein in Δtrk1,2 yeast could aid in the development of a high-throughput screening assay for molecules that target the retroviral protein.This study was supported by Grants PI PI05/00013 and PI08/0912 from Fondo de Investigación Sanitaria. L.H. and N.M. were holders of Predoctoral Fellowships from Instituto de Salud Carlos III.S

The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer

Three-dimensional (3D) epigenome remodeling is an important mechanism of gene deregulation in cancer. However, its potential as a target to counteract therapy resistance remains largely unaddressed. Here, we show that epigenetic therapy with decitabine (5-Aza-mC) suppresses tumor growth in xenograft models of pre-clinical metastatic estrogen receptor positive (ER+) breast tumor. Decitabine-induced genome-wide DNA hypomethylation results in large-scale 3D epigenome deregulation, including de-compaction of higher-order chromatin structure and loss of boundary insulation of topologically associated domains. Significant DNA hypomethylation associates with ectopic activation of ER-enhancers, gain in ER binding, creation of new 3D enhancer–promoter interactions and concordant up-regulation of ER-mediated transcription pathways. Importantly, long-term withdrawal of epigenetic therapy partially restores methylation at ER-enhancer elements, resulting in a loss of ectopic 3D enhancer–promoter interactions and associated gene repression. Our study illustrates the potential of epigenetic therapy to target ER+ endocrine-resistant breast cancer by DNA methylation-dependent rewiring of 3D chromatin interactions, which are associated with the suppression of tumor growth