De Sitter scattering amplitudes in the Born approximation

We present a covariant framework to compute scattering amplitudes and potentials in a de Sitter background. In this setting, we compute the potential of a graviton-mediated scattering process involving two very massive scalars at tree level. Although the obtained scattering potential reproduces the Newtonian potential at short distances, on Hubble-size length scales it is affected by the constant curvature: effectively, it yields a repulsive force at sub-Hubble distances. This can be attributed to the expansion of the de Sitter universe. Beyond the de Sitter horizon, the potential vanishes identically. Hence, the scattering amplitude unveils the geometric properties of de Sitter spacetime in a novel and nontrivial way

Quadratic gravity potentials in de Sitter spacetime from Feynman diagrams

We employ a manifestly covariant formalism to compute the tree-level amputated Green's function of non-minimally coupled scalar fields in quadratic gravity in a de Sitter background. We study this Green's function in the adiabatic limit, and construct the classical Newtonian potential. At short distances, the flat-spacetime Yukawa potential is reproduced, while the curvature gives rise to corrections to the potential at large distances. Beyond the Hubble radius, the potential vanishes identically, in agreement with the causal structure of de Sitter spacetime. For sub-Hubble distances, we investigate whether the modifications to the potential reproduce Modified Newtonian Dynamics.Comment: 34 pages, 9 figure

Dynamical diffeomorphisms

We construct a general effective dynamics for diffeomorphisms of spacetime, in a fixed external metric. Though related to familiar models of scalar fields as coordinates, our models have subtly different properties, both at kinematical and dynamical level. The energy-momentum tensor consists of two independently conserved parts. The background solution is the identity diffeomorphism and the energy-momentum tensor of this solution gives rise to an effective cosmological constant

Dynamical diffeomorphisms

We construct a general effective dynamics for diffeomorphisms of spacetime, in a fixed external metric. Though related to familiar models of scalar fields as coordinates, our models have subtly different properties, both at kinematical and dynamical level. The energy-momentum (EM) tensor consists of two independently conserved parts. The background solution is the identity diffeomorphism and the EM tensor of this solution gives rise to an effective cosmological constant

Relational observables in Asymptotically safe gravity

We introduce an approach to compute the renormalisation group flow of relational observables in quantum gravity which evolve from their microscopic expressions towards the full quantum expectation value. This is achieved by using the composite operator formalism of the functional renormalisation group. These methods can be applied to a large class of relational observables within a derivative expansion for different physical coordinate systems. As a first application we consider four scalar fields coupled to gravity to represent the physical coordinate frame from which relational observables can be constructed. At leading order of the derivative expansion the observables are the inverse relational metric and the relational scalar curvature. We evaluate their scaling dimensions at the fixed point, both in the standard renormalisation group scheme and in the essential scheme. This represents the first steps to describe running observables within asymptotic safety; this treatment can be generalised to other observables constructed from different tensors and in different physical coordinate systems.Comment: 29 pages, 2 figures; added references, corrected typo

An Italian Multicenter Perspective Harmonization Trial for the Assessment of MET Exon 14 Skipping Mutations in Standard Reference Samples

Lung cancer remains the leading cause of cancer deaths worldwide. International societies have promoted the molecular analysis of MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping for the clinical stratification of non-small cell lung cancer (NSCLC) patients. Different technical approaches are available to detect MET exon 14 skipping in routine practice. Here, the technical performance and reproducibility of testing strategies for MET exon 14 skipping carried out in various centers were evaluated. In this retrospective study, each institution received a set (n = 10) of a customized artificial formalin-fixed paraffin-embedded (FFPE) cell line (Custom METex14 skipping FFPE block) that harbored the MET exon 14 skipping mutation (Seracare Life Sciences, Milford, MA, USA), which was previously validated by the Predictive Molecular Pathology Laboratory at the University of Naples Federico II. Each participating institution managed the reference slides according to their internal routine workflow. MET exon 14 skipping was successfully detected by all participating institutions. Molecular analysis highlighted a median Cq cut off of 29.3 (ranging from 27.1 to 30.7) and 2514 (ranging from 160 to 7526) read counts for real-time polymerase chain reaction (RT-PCR) and NGS-based analyses, respectively. Artificial reference slides were a valid tool to harmonize technical workflows in the evaluation of MET exon 14 skipping molecular alterations in routine practice

Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

The Spectral Geometry of de Sitter Space in Asymptotic Safety

Within the functional renormalization group approach to Background Independent quantum gravity, we explore the scale dependent effective geometry of the de Sitter solution dS${}_4$. The investigation employs a novel approach whose essential ingredient is a modified spectral flow of the metric dependent d'Alembertian, or of similar hyperbolic kinetic operators. The corresponding one-parameter family of spectra and eigenfunctions encodes information about the nonperturbative backreaction of the dynamically gravitating vacuum fluctuations on the mean field geometry of the quantum spacetime. Used as a diagnostic tool, the power of the spectral flow method resides in its ability to identify the scale dependent subsets of field modes that supply the degrees of freedom which participate in the effective field theory description of the respective scale. A central result is that the ultraviolet of Quantum Einstein Gravity comprises far less effective degrees of freedom than predicted (incorrectly) by background dependent reasoning. Exploring the quantum spacetime's spatial geometry carried by physical fields, we find that 3-dimensional space disintegrates into a collection of coherent patches which individually can, but in their entirety cannot be described by one of the effective average actions occurring along the renormalization group trajectory. A natural concept of an entropy is introduced in order to quantify this fragmentation effect. Tentatively applied to the real Universe, surprising analogies to properties of the observed cosmic microwave background are uncovered. Furthermore, a set of distinguished field modes is found which, in principle, has the ability to transport information about the asymptotic fixed point regime from the ultraviolet, across almost the entire "scale history", to cosmological distances in the observed Universe.Comment: 64 pages, 13 figure