345 research outputs found
Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of MSD-819 (6-chloro-2-quinoxalinecarboxylic acid 1,4-dioxide)
Bulk Axions, Brane Back-reaction and Fluxes
Extra-dimensional models can involve bulk pseudo-Goldstone bosons (pGBs)
whose shift symmetry is explicitly broken only by physics localized on branes.
Reliable calculation of their low-energy potential is often difficult because
it requires details of the stabilization of the extra dimensions. In rugby ball
solutions, for which two compact extra dimensions are stabilized in the
presence of only positive-tension brane sources, the effects of brane
back-reaction can be computed explicitly. This allows the calculation of the
shape of the low-energy pGB potential and response of the extra dimensional
geometry as a function of the perturbing brane properties. If the
pGB-dependence is a small part of the total brane tension a very general
analysis is possible, permitting an exploration of how the system responds to
frustration when the two branes disagree on what the proper scalar vacuum
should be. We show how the low-energy potential is given by the sum of brane
tensions (in agreement with common lore) when only the brane tensions couple to
the pGB. We also show how a direct brane coupling to the flux stabilizing the
extra dimensions corrects this result in a way that does not simply amount to
the contribution of the flux to the brane tensions. We calculate the mass of
the would-be zero mode, and briefly describe several potential applications,
including a brane realization of `natural inflation,' and a dynamical mechanism
for suppressing the couplings of the pGB to matter localized on the branes.
Since the scalar can be light enough to be relevant to precision tests of
gravity (in a technically natural way) this mechanism can be relevant to
evading phenomenological bounds.Comment: 36 pages, JHEP styl
Transient silencing of antibiotic resistance by mutation represents a significant potential source of unanticipated therapeutic failure
Sporadic literature reports describe isolates of pathogenic bacteria that harbor an antibiotic resistance determinant but remain susceptible to the corresponding antibiotic as a consequence of a genetic defect. Such strains represent a source from which antibiotic resistance may reemerge to cause treatment failure in patients. Here, we report a systematic investigation into the prevalence and nature of this phenomenon, which we term silencing of antibiotic resistance by mutation (SARM). Instances of SARM were detected among 1,470 Staphylococcus aureus isolates through side-by-side comparison of antibiotic resistance genotype (as determined by whole-genome sequencing) versus phenotype (as assessed through susceptibility testing). Of the isolates analyzed, 152 (10.3%) harbored a silenced resistance gene, including 46 (3.1%) that exhibited SARM to currently deployed antistaphylococcal drugs. SARM resulted from diverse mutational events but most commonly through frameshift mutation of resistance determinants as a result of point deletion in poly(A) tracts. The majority (âŒ90%) of SARM strains reverted to antibiotic resistance at frequencies of â„10â9; thus, while appearing antibiotic sensitive in the clinical microbiology laboratory, most S. aureus isolates exhibiting SARM will revert to antibiotic resistance at frequencies achievable in patients. In view of its prevalence in a major pathogen, SARM represents a significant potential threat to the therapeutic efficacy of antibiotics
New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range
We survey the phenomenological constraints on abelian gauge bosons having
masses in the MeV to multi-GeV mass range (using precision electroweak
measurements, neutrino-electron and neutrino-nucleon scattering, electron and
muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic
parity violation, low-energy neutron scattering and primordial
nucleosynthesis). We compute their implications for the three parameters that
in general describe the low-energy properties of such bosons: their mass and
their two possible types of dimensionless couplings (direct couplings to
ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue
that gauge bosons with very small couplings to ordinary fermions in this mass
range are natural in string compactifications and are likely to be generic in
theories for which the gravity scale is systematically smaller than the Planck
mass - such as in extra-dimensional models - because of the necessity to
suppress proton decay. Furthermore, because its couplings are weak, in the
low-energy theory relevant to experiments at and below TeV scales the charge
gauged by the new boson can appear to be broken, both by classical effects and
by anomalies. In particular, if the new gauge charge appears to be anomalous,
anomaly cancellation does not also require the introduction of new light
fermions in the low-energy theory. Furthermore, the charge can appear to be
conserved in the low-energy theory, despite the corresponding gauge boson
having a mass. Our results reduce to those of other authors in the special
cases where there is no kinetic mixing or there is no direct coupling to
ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which
appears in JHE
Cryptic silver resistance is prevalent and readily activated in certain Gram-negative pathogens
Objectives: To assess the prevalence of cryptic silver (Ag+) resistance amongst clinical isolates of Gram-negative bacteria, and to examine how overt Ag+ resistance becomes activated in such strains. Methods: Established methods were used to determine the susceptibility of 444 recent clinical isolates to Ag+, and to evaluate the potential for overt Ag+ resistance to emerge from these isolates by spontaneous mutation. The genetic basis for Ag+ resistance was investigated using PCR amplification and DNA sequencing. Results: None of the isolates tested displayed overt Ag+ resistance. However, upon silver challenge, high-level Ag+ resistance (silver nitrate MIC >128 mg/L) was selected at high frequency (10ÂŻâ· to 10ÂŻâž) in Ë76% isolates of Enterobacter spp., Ë58% isolates of Klebsiella spp., and Ë0.7% isolates of E. coli. All strains in which Ag+ resistance could be selected harboured the sil operon, with resistance in each case apparently resulting from activation of this system as a consequence of a single missense mutation in silS. By contrast, Ag+ resistance could not be selected in isolates lacking sil, which included all tested representatives of Acinetobacter baumannii, Pseudomonas aeruginosa, Proteus spp and Citrobacter spp. Conclusions: Whilst overt Ag+ resistance in Gram-negative pathogens is uncommon, cryptic Ag+ resistance pertaining to the sil operon is prevalent and readily activated in particular genera (Enterobacter and Klebsiella)
Smooth tensionful higher-codimensional brane worlds with bulk and brane form fields
Completely regular tensionful codimension-n brane world solutions are
discussed, where the core of the brane is chosen to be a thin codimension-(n-1)
shell in an infinite volume flat bulk, and an Einstein-Hilbert term localized
on the brane is included (Dvali-Gabadadze-Porrati models). In order to support
such localized sources we enrich the vacuum structure of the brane by the
inclusion of localized form fields. We find that phenomenological constraints
on the size of the internal core seem to impose an upper bound to the brane
tension. Finite transverse-volume smooth solutions are also discussed.Comment: 1+14 pages, 2 figures; section 2.3 improved, typos corrected and
references added. Published versio
The influence of D-branes' backreaction upon gravitational interactions between open strings
We argue that gravitational interactions between open strings ending on
D3-branes are largely shaped by the D3-branes' backreaction. To this end we
consider classical open strings coupled to general relativity in Poincare AdS5
backgrounds. We compute the linear gravitational backreaction of a static
string extending up to the Poincare horizon, and deduce the potential energy
between two such strings. If spacetime is non-compact, we find that the
gravitational potential energy between parallel open strings is independent of
the strings' inertial masses and goes like 1/r at large distance r. If the
space transverse to the D3-branes is suitably compactified, a collective mode
of the graviton propagates usual four-dimensional gravity. In that case the
backreaction of the D3-branes induces a correction to the Newtonian potential
energy that violates the equivalence principle. The observed enhancement of the
gravitational attraction is specific to string theory; there is no similar
effect for point-particles.Comment: 28 pages, 7 figures. Typos corrected, minor addition
Emergent Gauge Fields in Holographic Superconductors
Holographic superconductors have been studied so far in the absence of
dynamical electromagnetic fields, namely in the limit in which they coincide
with holographic superfluids. It is possible, however, to introduce dynamical
gauge fields if a Neumann-type boundary condition is imposed on the
AdS-boundary. In 3+1 dimensions, the dual theory is a 2+1 dimensional CFT whose
spectrum contains a massless gauge field, signaling the emergence of a gauge
symmetry. We study the impact of a dynamical gauge field in vortex
configurations where it is known to significantly affect the energetics and
phase transitions. We calculate the critical magnetic fields H_c1 and H_c2,
obtaining that holographic superconductors are of Type II (H_c1 < H_c2). We
extend the study to 4+1 dimensions where the gauge field does not appear as an
emergent phenomena, but can be introduced, by a proper renormalization, as an
external dynamical field. We also compare our predictions with those arising
from a Ginzburg-Landau theory and identify the generic properties of Abrikosov
vortices in holographic models.Comment: 19 pages, 14 figures, few comments added, version published in JHE
Effective AdS/renormalized CFT
For an effective AdS theory, we present a simple prescription to compute the
renormalization of its dual boundary field theory. In particular, we define
anomalous dimension holographically as the dependence of the wave-function
renormalization factor on the radial cutoff in the Poincare patch of AdS. With
this definition, the anomalous dimensions of both single- and double- trace
operators are calculated. Three different dualities are considered with the
field theory being CFT, CFT with a double-trace deformation and spontaneously
broken CFT. For the second dual pair, we compute scaling corrections at the UV
and IR fixed points of the RG flow triggered by the double-trace deformation.
For the last case, we discuss whether our prescription is sensitive to the AdS
interior or equivalently, the IR physics of the dual field theory.Comment: 20 pages, 3 figure
Effects of heavy modes on vacuum stability in supersymmetric theories
We study the effects induced by heavy fields on the masses of light fields in
supersymmetric theories, under the assumption that the heavy mass scale is much
higher than the supersymmetry breaking scale. We show that the square-masses of
light scalar fields can get two different types of significant corrections when
a heavy multiplet is integrated out. The first is an indirect level-repulsion
effect, which may arise from heavy chiral multiplets and is always negative.
The second is a direct coupling contribution, which may arise from heavy vector
multiplets and can have any sign. We then apply these results to the sGoldstino
mass and study the implications for the vacuum metastability condition. We find
that the correction from heavy chiral multiplets is always negative and tends
to compromise vacuum metastability, whereas the contribution from heavy vector
multiplets is always positive and tends on the contrary to reinforce it. These
two effects are controlled respectively by Yukawa couplings and gauge charges,
which mix one heavy and two light fields respectively in the superpotential and
the Kahler potential. Finally we also comment on similar effects induced in
soft scalar masses when the heavy multiplets couple both to the visible and the
hidden sector.Comment: LaTex, 24 pages, no figures; v2 some comments and references adde
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