181 research outputs found
Antimalarial 4(1H)-pyridones bind to the Qisite of cytochromebc1
Cytochrome bc1 is a proven drug target in the prevention and treatment of malaria. The rise in drug-resistant strains of Plasmodium falciparum, the organism responsible for malaria, has generated a global effort in designing new classes of drugs. Much of the design/redesign work on overcoming this resistance has been focused on compounds that are presumed to bind the Qo site (one of two potential binding sites within cytochrome bc1) using the known crystal structure of this large membrane-bound macromolecular complex via in silico modeling. Cocrystallization of the cytochrome bc1 complex with the 4(1H)-pyridone class of inhibitors, GSK932121 and GW844520, that have been shown to be potent antimalarial agents in vivo, revealed that these inhibitors do not bind at the Qo site but bind at the Qi site. The discovery that these compounds bind at the Qi site may provide a molecular explanation for the cardiotoxicity and eventual failure of GSK932121 in phase-1 clinical trial and highlight the need for direct experimental observation of a compound bound to a target site before chemical optimization and development for clinical trials. The binding of the 4(1H)-pyridone class of inhibitors to Qi also explains the ability of this class to overcome parasite Qo-based atovaquone resistance and provides critical structural information for future design of new selective compounds with improved safety profiles
The -theorem and the Asymptotics of 4D Quantum Field Theory
We study the possible IR and UV asymptotics of 4D Lorentz invariant unitary
quantum field theory. Our main tool is a generalization of the
Komargodski-Schwimmer proof for the -theorem. We use this to rule out a
large class of renormalization group flows that do not asymptote to conformal
field theories in the UV and IR. We show that if the IR (UV) asymptotics is
described by perturbation theory, all beta functions must vanish faster than
as (). This implies that the
only possible asymptotics within perturbation theory is conformal field theory.
In particular, it rules out perturbative theories with scale but not conformal
invariance, which are equivalent to theories with renormalization group
pseudocycles. Our arguments hold even for theories with gravitational
anomalies. We also give a non-perturbative argument that excludes theories with
scale but not conformal invariance. This argument holds for theories in which
the stress-energy tensor is sufficiently nontrivial in a technical sense that
we make precise.Comment: 41 pages, 2 figures. v2: Arguments clarified, some side comments
corrected, connection to previous work by Jack and Osborn described,
conclusions unaffecte
Black Holes in Gravity with Conformal Anomaly and Logarithmic Term in Black Hole Entropy
We present a class of exact analytic and static, spherically symmetric black
hole solutions in the semi-classical Einstein equations with Weyl anomaly. The
solutions have two branches, one is asymptotically flat and the other
asymptotically de Sitter. We study thermodynamic properties of the black hole
solutions and find that there exists a logarithmic correction to the well-known
Bekenstein-Hawking area entropy. The logarithmic term might come from non-local
terms in the effective action of gravity theories. The appearance of the
logarithmic term in the gravity side is quite important in the sense that with
this term one is able to compare black hole entropy up to the subleading order,
in the gravity side and in the microscopic statistical interpretation side.Comment: Revtex, 10 pages. v2: minor changes and to appear in JHE
Factorization Properties of Soft Graviton Amplitudes
We apply recently developed path integral resummation methods to perturbative
quantum gravity. In particular, we provide supporting evidence that eikonal
graviton amplitudes factorize into hard and soft parts, and confirm a recent
hypothesis that soft gravitons are modelled by vacuum expectation values of
products of certain Wilson line operators, which differ for massless and
massive particles. We also investigate terms which break this factorization,
and find that they are subleading with respect to the eikonal amplitude. The
results may help in understanding the connections between gravity and gauge
theories in more detail, as well as in studying gravitational radiation beyond
the eikonal approximation.Comment: 35 pages, 5 figure
Trace anomalies in chiral theories revisited
Motivated by the search for possible CP violating terms in the trace of the
energy-momentum tensor in theories coupled to gravity we revisit the problem of trace
anomalies in chiral theories. We recalculate the latter and ascertain that in the trace of
the energy-momentum tensor of theories with chiral fermions at one-loop the Pontryagin
density appears with an imaginary coefficient. We argue that this may break unitarity, in
which case the trace anomaly has to be used as a selective criterion for theories, analogous
to the chiral anomalies in gauge theories. We analyze some remarkable consequences of
this fact, that seem to have been overlooked in the literature
Quantum gravitational corrections for spinning particles
We calculate the quantum corrections to the gauge-invariant gravitational potentials of spinning particles in flat space, induced by loops of both massive and massless matter fields of various types. While the corrections to the Newtonian potential induced by massless conformal matter for spinless particles are well-known, and the same corrections due to massless minimally coupled scalars [Class. Quant. Grav. 27 (2010) 245008], massless non-conformal scalars [Phys. Rev. D 87 (2013) 104027] and massive scalars, fermions and vector bosons [Phys. Rev. D 91 (2015) 064047] have been recently derived, spinning particles receive additional corrections which are the subject of the present work. We give both fully analytic results valid for all distances from the particle, and present numerical results as well as asymptotic expansions. At large distances from the particle, the corrections due to massive fields are exponentially suppressed in comparison to the corrections from massless fields, as one would expect. However, a surprising result of our analysis is that close to the particle itself, on distances comparable to the Compton wavelength of the massive fields running in the loops, these corrections can be enhanced with respect to the massless case
Quantum Fluctuations and the Unruh Effect in Strongly-Coupled Conformal Field Theories
Through the AdS/CFT correspondence, we study a uniformly accelerated quark in
the vacuum of strongly-coupled conformal field theories in various dimensions,
and determine the resulting stochastic fluctuations of the quark trajectory.
From the perspective of an inertial observer, these are quantum fluctuations
induced by the gluonic radiation emitted by the accelerated quark. From the
point of view of the quark itself, they originate from the thermal medium
predicted by the Unruh effect. We scrutinize the relation between these two
descriptions in the gravity side of the correspondence, and show in particular
that upon transforming the conformal field theory from Rindler space to the
open Einstein universe, the acceleration horizon disappears from the boundary
theory but is preserved in the bulk. This transformation allows us to directly
connect our calculation of radiation-induced fluctuations in vacuum with the
analysis by de Boer et al. of the Brownian motion of a quark that is on average
static within a thermal medium. Combining this same bulk transformation with
previous results of Emparan, we are also able to compute the stress-energy
tensor of the Unruh thermal medium.Comment: 1+31 pages; v2: reference adde
Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory
This article is meant as a summary and introduction to the ideas of effective
field theory as applied to gravitational systems.
Contents:
1. Introduction
2. Effective Field Theories
3. Low-Energy Quantum Gravity
4. Explicit Quantum Calculations
5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living
Reviews of Relativit
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