Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: Towards the development of potential dual action antimalarials

A series of cinnamic acid/4-aminoquinoline conjugates conceived to link, through a proper retro-enantio dipeptide, a heterocyclic core known to prevent hemozoin formation, to a trans-cinnamic acid motif capable of inhibiting enzyme catalytic Cys residues, were synthesized as potential dual-action antimalarials. The effect of amino acid configuration and the absence of the dipeptide spacer were also assessed. The replacement of the D-amino acids by their natural L counterparts led to a decrease in both anti-plasmodial and falcipain inhibitory activity, suggesting that the former are preferable. Molecules with such spacer were active against blood-stage Plasmodium falciparum, in vitro, and hemozoin formation, implying that the dipeptide has a key role in mediating these two activities. In turn, compounds without spacer were better falcipain-2 inhibitors, likely because these compounds are smaller and have their vinyl bonds in closer vicinity to the catalytic Cys, as suggested by molecular modeling calculations. These novel conjugates constitute promising leads for the development of new antiplasmodials targeted at blood-stage malaria parasites

Regge calculus from a new angle

In Regge calculus space time is usually approximated by a triangulation with flat simplices. We present a formulation using simplices with constant sectional curvature adjusted to the presence of a cosmological constant. As we will show such a formulation allows to replace the length variables by 3d or 4d dihedral angles as basic variables. Moreover we will introduce a first order formulation, which in contrast to using flat simplices, does not require any constraints. These considerations could be useful for the construction of quantum gravity models with a cosmological constant.Comment: 8 page

Area-angle variables for general relativity

We introduce a modified Regge calculus for general relativity on a triangulated four dimensional Riemannian manifold where the fundamental variables are areas and a certain class of angles. These variables satisfy constraints which are local in the triangulation. We expect the formulation to have applications to classical discrete gravity and non-perturbative approaches to quantum gravity.Comment: 7 pages, 1 figure. v2 small changes to match published versio

Gauge invariant perturbations around symmetry reduced sectors of general relativity: applications to cosmology

We develop a gauge invariant canonical perturbation scheme for perturbations around symmetry reduced sectors in generally covariant theories, such as general relativity. The central objects of investigation are gauge invariant observables which encode the dynamics of the system. We apply this scheme to perturbations around a homogeneous and isotropic sector (cosmology) of general relativity. The background variables of this homogeneous and isotropic sector are treated fully dynamically which allows us to approximate the observables to arbitrary high order in a self--consistent and fully gauge invariant manner. Methods to compute these observables are given. The question of backreaction effects of inhomogeneities onto a homogeneous and isotropic background can be addressed in this framework. We illustrate the latter by considering homogeneous but anisotropic Bianchi--I cosmologies as perturbations around a homogeneous and isotropic sector.Comment: 39 pages, 1 figur

Towards computational insights into the large-scale structure of spin foams

Understanding the large-scale physics is crucial for the spin foam approach to quantum gravity. We tackle this challenge from a statistical physics perspective using simplified, yet feature-rich models. In particular, this allows us to explicitly answer whether broken symmetries will be restored by renormalization: We observe a weak phase transition in both Migdal-Kadanoff and tensor network renormalization. In this work we give a concise presentation of the concepts, results and promises of this new direction of research.Comment: 10 pages, 9 figures, to be published in proceedings of the Loops'11 Madrid international conference on quantum gravit

Towards computational insights into the large-scale structure of spin foams

Understanding the large-scale physics is crucial for the spin foam approach to quantum gravity. We tackle this challenge from a statistical physics perspective using simplified, yet feature-rich models. In particular, this allows us to explicitly answer whether broken symmetries will be restored by renormalization: We observe a weak phase transition in both Migdal-Kadanoff and tensor network renormalization. In this work we give a concise presentation of the concepts, results and promises of this new direction of research.Comment: 10 pages, 9 figures, to be published in proceedings of the Loops'11 Madrid international conference on quantum gravit

Towards computational insights into the large-scale structure of spin foams

Understanding the large-scale physics is crucial for the spin foam approach to quantum gravity. We tackle this challenge from a statistical physics perspective using simplified, yet feature-rich models. In particular, this allows us to explicitly answer whether broken symmetries will be restored by renormalization: We observe a weak phase transition in both Migdal-Kadanoff and tensor network renormalization. In this work we give a concise presentation of the concepts, results and promises of this new direction of research.Comment: 10 pages, 9 figures, to be published in proceedings of the Loops'11 Madrid international conference on quantum gravit

(Broken) Gauge Symmetries and Constraints in Regge Calculus

We will examine the issue of diffeomorphism symmetry in simplicial models of (quantum) gravity, in particular for Regge calculus. We find that for a solution with curvature there do not exist exact gauge symmetries on the discrete level. Furthermore we derive a canonical formulation that exactly matches the dynamics and hence symmetries of the covariant picture. In this canonical formulation broken symmetries lead to the replacements of constraints by so--called pseudo constraints. These considerations should be taken into account in attempts to connect spin foam models, based on the Regge action, with canonical loop quantum gravity, which aims at implementing proper constraints. We will argue that the long standing problem of finding a consistent constraint algebra for discretized gravity theories is equivalent to the problem of finding an action with exact diffeomorphism symmetries. Finally we will analyze different limits in which the pseudo constraints might turn into proper constraints. This could be helpful to infer alternative discretization schemes in which the symmetries are not broken.Comment: 32 pages, 15 figure

From the discrete to the continuous - towards a cylindrically consistent dynamics

Discrete models usually represent approximations to continuum physics. Cylindrical consistency provides a framework in which discretizations mirror exactly the continuum limit. Being a standard tool for the kinematics of loop quantum gravity we propose a coarse graining procedure that aims at constructing a cylindrically consistent dynamics in the form of transition amplitudes and Hamilton's principal functions. The coarse graining procedure, which is motivated by tensor network renormalization methods, provides a systematic approximation scheme towards this end. A crucial role in this coarse graining scheme is played by embedding maps that allow the interpretation of discrete boundary data as continuum configurations. These embedding maps should be selected according to the dynamics of the system, as a choice of embedding maps will determine a truncation of the renormalization flow.Comment: 22 page

Phase space descriptions for simplicial 4d geometries

Starting from the canonical phase space for discretised (4d) BF-theory, we implement a canonical version of the simplicity constraints and construct phase spaces for simplicial geometries. Our construction allows us to study the connection between different versions of Regge calculus and approaches using connection variables, such as loop quantum gravity. We find that on a fixed triangulation the (gauge invariant) phase space associated to loop quantum gravity is genuinely larger than the one for length and even area Regge calculus. Rather, it corresponds to the phase space of area-angle Regge calculus, as defined by Dittrich and Speziale in [arXiv:0802.0864] (prior to the imposition of gluing constraints, that ensure the metricity of the triangulation). We argue that this is due to the fact that the simplicity constraints are not fully implemented in canonical loop quantum gravity. Finally, we show that for a subclass of triangulations one can construct first class Hamiltonian and Diffeomorphism constraints leading to flat 4d space-times.Comment: corrected structure constants, several references ad