55 research outputs found

    The Momentum Constraints of General Relativity and Spatial Conformal Isometries

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    Transverse-tracefree (TT-) tensors on (R3,gab)({\bf R}^3,g_{ab}), with gabg_{ab} an asymptotically flat metric of fast decay at infinity, are studied. When the source tensor from which these TT tensors are constructed has fast fall-off at infinity, TT tensors allow a multipole-type expansion. When gabg_{ab} has no conformal Killing vectors (CKV's) it is proven that any finite but otherwise arbitrary set of moments can be realized by a suitable TT tensor. When CKV's exist there are obstructions -- certain (combinations of) moments have to vanish -- which we study.Comment: 16 page

    Discrimination of Potent Inhibitors of Toxoplasma gondii Enoyl-Acyl Carrier Protein Reductase by a Thermal Shift Assay

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    Many microbial pathogens rely on a type II fatty acid synthesis (FASII) pathway that is distinct from the type I pathway found in humans. Enoyl-acyl carrier protein reductase (ENR) is an essential FASII pathway enzyme and the target of a number of antimicrobial drug discovery efforts. The biocide triclosan is established as a potent inhibitor of ENR and has been the starting point for medicinal chemistry studies. We evaluated a series of triclosan analogues for their ability to inhibit the growth of Toxoplasma gondii, a pervasive human pathogen, and its ENR enzyme (TgENR). Several compounds that inhibited TgENR at low nanomolar concentrations were identified but could not be further differentiated because of the limited dynamic range of the TgENR activity assay. Thus, we adapted a thermal shift assay (TSA) to directly measure the dissociation constant (Kd) of the most potent inhibitors identified in this study as well as inhibitors from previous studies. Furthermore, the TSA allowed us to determine the mode of action of these compounds in the presence of the reduced nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide (NAD+) cofactor. We found that all of the inhibitors bind to a TgENR–NAD+ complex but that they differed in their dependence on NAD+ concentration. Ultimately, we were able to identify compounds that bind to the TgENR–NAD+ complex in the low femtomolar range. This shows how TSA data combined with enzyme inhibition, parasite growth inhibition data, and ADMET predictions allow for better discrimination between potent ENR inhibitors for the future development of medicine

    Noncommutative Topological Theories of Gravity

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    The possibility of noncommutative topological gravity arising in the same manner as Yang-Mills theory is explored. We use the Seiberg-Witten map to construct such a theory based on a SL(2,C) complex connection, from which the Euler characteristic and the signature invariant are obtained. This gives us a way towards the description of noncommutative gravitational instantons as well as noncommutative local gravitational anomalies.Comment: 17+1 pages, LaTeX, no figures, some clarifications, comments and references added, style improve

    Dirac's Observables for the Rest-Frame Instant Form of Tetrad Gravity in a Completely Fixed 3-Orthogonal Gauge

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    We define the {\it rest-frame instant form} of tetrad gravity restricted to Christodoulou-Klainermann spacetimes. After a study of the Hamiltonian group of gauge transformations generated by the 14 first class constraints of the theory, we define and solve the multitemporal equations associated with the rotation and space diffeomorphism constraints, finding how the cotriads and their momenta depend on the corresponding gauge variables. This allows to find quasi-Shanmugadhasan canonical transformation to the class of 3-orthogonal gauges and to find the Dirac observables for superspace in these gauges. The construction of the explicit form of the transformation and of the solution of the rotation and supermomentum constraints is reduced to solve a system of elliptic linear and quasi-linear partial differential equations. We then show that the superhamiltonian constraint becomes the Lichnerowicz equation for the conformal factor of the 3-metric and that the last gauge variable is the momentum conjugated to the conformal factor. The gauge transformations generated by the superhamiltonian constraint perform the transitions among the allowed foliations of spacetime, so that the theory is independent from its 3+1 splittings. In the special 3-orthogonal gauge defined by the vanishing of the conformal factor momentum we determine the final Dirac observables for the gravitational field even if we are not able to solve the Lichnerowicz equation. The final Hamiltonian is the weak ADM energy restricted to this completely fixed gauge.Comment: RevTeX file, 141 page
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