Fluctuations of an evaporating black hole from back reaction of its Hawking radiation: Questioning a premise in earlier work

This paper delineates the first steps in a systematic quantitative study of the spacetime fluctuations induced by quantum fields in an evaporating black hole. We explain how the stochastic gravity formalism can be a useful tool for that purpose within a low-energy effective field theory approach to quantum gravity. As an explicit example we apply it to the study of the spherically-symmetric sector of metric perturbations around an evaporating black hole background geometry. For macroscopic black holes we find that those fluctuations grow and eventually become important when considering sufficiently long periods of time (of the order of the evaporation time), but well before the Planckian regime is reached. In addition, the assumption of a simple correlation between the fluctuations of the energy flux crossing the horizon and far from it, which was made in earlier work on spherically-symmetric induced fluctuations, is carefully analyzed and found to be invalid. Our analysis suggests the existence of an infinite amplitude for the fluctuations of the horizon as a three-dimensional hypersurface. We emphasize the need for understanding and designing operational ways of probing quantum metric fluctuations near the horizon and extracting physically meaningful information.Comment: 10 pages, REVTeX; minor changes, a few references added and a brief discussion of their relevance included. To appear in the proceedings of the 10th Peyresq meeting. Dedicated to Rafael Sorkin on the occasion of his 60th birthda

Stress tensor fluctuations in de Sitter spacetime

The two-point function of the stress tensor operator of a quantum field in de Sitter spacetime is calculated for an arbitrary number of dimensions. We assume the field to be in the Bunch-Davies vacuum, and formulate our calculation in terms of de Sitter-invariant bitensors. Explicit results for free minimally coupled scalar fields with arbitrary mass are provided. We find long-range stress tensor correlations for sufficiently light fields (with mass m much smaller than the Hubble scale H), namely, the two-point function decays at large separations like an inverse power of the physical distance with an exponent proportional to m^2/H^2. In contrast, we show that for the massless case it decays at large separations like the fourth power of the physical distance. There is thus a discontinuity in the massless limit. As a byproduct of our work, we present a novel and simple geometric interpretation of de Sitter-invariant bitensors for pairs of points which cannot be connected by geodesics.Comment: 35 pages, 4 figure

Inhibitors of trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight into the potential specificity of the interaction with the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors may represent a valuable strategy for drug discovery against T. cruzi