Towards a formal description of the collapse approach to the inflationary origin of the seeds of cosmic structure

Inflation plays a central role in our current understanding of the universe. According to the standard viewpoint, the homogeneous and isotropic mode of the inflaton field drove an early phase of nearly exponential expansion of the universe, while the quantum fluctuations (uncertainties) of the other modes gave rise to the seeds of cosmic structure. However, if we accept that the accelerated expansion led the universe into an essentially homogeneous and isotropic space-time, with the state of all the matter fields in their vacuum (except for the zero mode of the inflaton field), we can not escape the conclusion that the state of the universe as a whole would remain always homogeneous and isotropic. It was recently proposed in [A. Perez, H. Sahlmann and D. Sudarsky, "On the quantum origin of the seeds of cosmic structure," Class. Quant. Grav. 23, 2317-2354 (2006)] that a collapse (representing physics beyond the established paradigm, and presumably associated with a quantum-gravity effect a la Penrose) of the state function of the inflaton field might be the missing element, and thus would be responsible for the emergence of the primordial inhomogeneities. Here we will discuss a formalism that relies strongly on quantum field theory on curved space-times, and within which we can implement a detailed description of such a process. The picture that emerges clarifies many aspects of the problem, and is conceptually quite transparent. Nonetheless, we will find that the results lead us to argue that the resulting picture is not fully compatible with a purely geometric description of space-time.Comment: 53 pages, no figures. Revision to match the published versio

Relativistic hydrodynamics with sources for cosmological K-fluids

We consider hydrodynamics with non conserved number of particles and show that it can be modeled with effective fluid Lagrangians which explicitly depend on the velocity potentials. For such theories, the {}``shift symetry'' $\phi\to\phi+$const. leading to the conserved number of fluid particles in conventional hydrodynamics is globaly broken and, as a result, the non conservation of particle number appears as a source term in the continuity equation. The particle number non-conservation is balanced by the entropy change, with both the entropy and the source term expresed in terms of the fluid velocity potential. Equations of hydrodynamics are derived using a modified version of Schutz's variational principle method. Examples of fluids described by such Lagrangians (tachyon condensate, k-essence) in spatially flat isotropic universe are briefly discussed.Comment: 9 pages, no figures. Title changed. Minor corrections. To appear in Int. Jour. Mod. Phys.

Pure kinetic k-essence as the cosmic speed-up

In this paper, we consider three types of k-essence. These k-essence models were presented in the parametric forms. The exact analytical solutions of the corresponding equations of motion are found. It is shown that these k-essence models for the presented solutions can give rise to cosmic acceleration.Comment: 10 pages, typos corrected, main results remain the same, minor changes to match IJTP accepted versio

Oxidative Stress and Cellular Senescence Are Involved in the Aging Kidney

Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non‐invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senes-cence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was ob-served by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, character-ized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progressionThis research was funded by grants from the Instituto de Salud Carlos III (ISCIII); Fondos FEDER European Union (PI17/00119, PI20/00140; and DTS20/00083 to M.R.-O.; PI18/01133 to A.M.R.); Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R.-D.); Red de Investigación Renal REDINREN: RD16/0009/0003 and RICORS program to RICORS2040 496 (RD21/0005), to M.R.-O., Sociedad Española de Nefrología; “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD3751 to M.R.-O.); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); Juan de la Cierva incorporacion grant: IJC2018-035187-I to S.R.-M.; innovation program under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMProvePD ID: 812699) to M.R.-O.; and Fundacion Conchita Rabago to L.T.-

Statins: Could an old friend help the fight against COVID-19?

This is the peer reviewed version of the following article: "Statins: Could an old friend help the fight against COVID-19?" . British Journal of Pharmacology (2020): 19 June, which has been published in final form at https://doi.org/10.1111/bph.15166. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versionshe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomesThis work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigación Renal (REDINREN): RD16/0009, to M.R-O, PI17/01495 to J.E, PI18/01133 to AMR, PI19/00815 to A.O); Comunidad de Madrid (“NOVELREN” B2017/BMD3751 to M.R-O, B2017/BMD-3686 CIFRA2-CM to A.O); Spanish Ministry of Economy and Competitiveness MINECO (DTS17/00203, DTS19/00093) to J,E; “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R-O and SR-M); ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O; The “Sara Borrell” postdoctoral training program of the ISCIII supported the salary of SR-M (CD19/00021), IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.O

A mathematical analysis of the evolution of perturbations in a modified Chaplygin gas model

One approach in modern cosmology consists in supposing that dark matter and dark energy are different manifestations of a single `quartessential' fluid. Following such idea, this work presents a study of the evolution of perturbations of density in a flat cosmological model with a modified Chaplygin gas acting as a single component. Our goal is to obtain properties of the model which can be used to distinguish it from another cosmological models which have the same solutions for the general evolution of the scale factor of the universe, without the construction of the power spectrum. Our analytical results, which alone can be used to uniquely characterize the specific model studied in our work, show that the evolution of the density contrast can be seen, at least in one particular case, as composed by a spheroidal wave function. We also present a numerical analysis which clearly indicates as one interesting feature of the model the appearence of peaks in the evolution of the density constrast.Comment: 21 pages, accepted for publication in General Relativity and Gravitatio

The Imperfect Fluid behind Kinetic Gravity Braiding

We present a standard hydrodynamical description for non-canonical scalar field theories with kinetic gravity braiding. In particular, this picture applies to the simplest galileons and k-essence. The fluid variables not only have a clear physical meaning but also drastically simplify the analysis of the system. The fluid carries charges corresponding to shifts in field space. This shift-charge current contains a spatial part responsible for diffusion of the charges. Moreover, in the incompressible limit, the equation of motion becomes the standard diffusion equation. The fluid is indeed imperfect because the energy flows neither along the field gradient nor along the shift current. The fluid has zero vorticity and is not dissipative: there is no entropy production, the energy-momentum is exactly conserved, the temperature vanishes and there is no shear viscosity. Still, in an expansion around a perfect fluid one can identify terms which correct the pressure in the manner of bulk viscosity. We close by formulating the non-trivial conditions for the thermodynamic equilibrium of this imperfect fluid.Comment: 23 pages plus appendices. New version includes extended discussion on diffusion and dynamics in alternative frames, as well as additional references. v3 reflects version accepted for publication in JHEP: minor comments added regarding suitability to numerical approache

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

The collapse of the wave function in the joint metric-matter quantization for inflation

It has been argued that the standard inflationary scenario suffers from a serious deficiency as a model for the origin of the seeds of cosmic structure: it can not truly account for the transition from an early homogeneous and isotropic stage to another one lacking such symmetries. The issue has often been thought as a standard instance of the "quantum measurement problem", but as has been recently argued by some of us the situation reaches a critical level in the cosmological context of interest here. This has lead to a proposal in which the standard paradigm is supplemented by a hypothesis concerning the self-induced dynamical collapse of the wave function, as representing the physical mechanism through which such change of symmetry is brought forth. This proposal was formulated within the context of semiclassical gravity. Here we investigate an alternative realization of such idea implemented directly within the standard analysis in terms of a quantum field jointly describing the inflaton and metric perturbations, the so called Mukhanov-Sasaki variable. We show that even though the prescription is quite different, the theoretical predictions include some deviations from the standard ones, which are indeed very similar to those found in the early studies. We briefly discuss the differences between the two at both, the conceptual and practical levels.Comment: 31 pages, 6 figures. Replaced to match the published versio

Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes

Acute kidney injury (AKI) is more frequent in elderly patients. Mechanisms contributing to AKI (tubular cell death, inflammatory cell infiltration, impaired mitochondrial function, and prolonged cell-cycle arrest) have been linked to cellular senescence, a process implicated in regeneration failure and progression to fibrosis. However, the molecular and pathological basis of the age-related increase in AKI incidence is not completely understood. To explore these mechanisms, experimental AKI was induced by folic acid (FA) administration in young (3-months-old) and old (1-year-old) mice, and kidneys were evaluated in the early phase of AKI, at 48 h. Tubular damage score, KIM-1 expression, the recruitment of infiltrating immune cells (mainly neutrophils and macrophages) and proinflammatory gene expression were higher in AKI kidneys of old than of young mice. Tubular cell death in FA-AKI involves several pathways, such as regulated necrosis and apoptosis. Ferroptosis and necroptosis cell-death pathways were upregulated in old AKI kidneys. In contrast, caspase-3 activation was only found in young but not in old mice. Moreover, the antiapoptotic factor BCL-xL was significantly overexpressed in old, injured kidneys, suggesting an age-related apoptosis suppression. AKI kidneys displayed evidence of cellular senescence, such as increased levels of cyclin dependent kinase inhibitors p16ink4a and p21cip1, and of the DNA damage response marker γH2AX. Furthermore, p21cip1 mRNA expression and nuclear staining for p21cip1 and γH2AX were higher in old than in young FA-AKI mice, as well as the expression of senescence-associated secretory phenotype (SASP) components (Il-6, Tgfb1, Ctgf, and Serpine1). Interestingly, some infiltrating immune cells were p21 or γH2AX positive, suggesting that molecular senescence in the immune cells (“immunosenescence”) are involved in the increased severity of AKI in old mice. In contrast, expression of renal protective factors was dramatically downregulated in old AKI mice, including the antiaging factor Klotho and the mitochondrial biogenesis driver PGC-1α. In conclusion, aging resulted in more severe AKI after the exposure to toxic compounds. This increased toxicity may be related to magnification of proinflammatory-related pathways in older mice, including a switch to a proinflammatory cell death (necroptosis) instead of apoptosis, and overactivation of cellular senescence of resident renal cells and infiltrating inflammatory cells