2,221 research outputs found
Vanishing conductivity of quantum solitons in polyacetylene
Quantum solitons or polarons are supposed to play a crucial role in the
electric conductivity of polyacetylene, in the intermediate doping regime. We
present an exact fully quantized calculation of the quantum soliton
conductivity in polyacetylene and show that it vanishes exactly. This is
obtained by applying a general method of soliton quantization, based on
order-disorder duality, to a Z(2)-symmetric complex extension of the TLM
dimerization effective field theory. We show that, in this theory,
polyacetylene solitons are sine-Gordon solitons in the phase of the complex
field.Comment: To appear in J. Phys. A: Math. Theor., 15 page
Exact Asymptotic Behaviour of Fermion Correlation Functions in the Massive Thirring Model
We obtain an exact asymptotic expression for the two-point fermion
correlation functions in the massive Thirring model (MTM) and show that, for
, they reproduce the exactly known corresponding functions of the
massless theory, explicitly confirming the irrelevance of the mass term at this
point. This result is obtained by using the Coulomb gas representation of the
fermionic MTM correlators in the bipolar coordinate system.Comment: To appear in J. Phys. A: Math. Gen. 12 page
Frequentist Interpretation of Probability
Three series of azole piperazine derivatives that mimic dicyclotyrosine (cYY), the natural substrate of the essential Mycobacterium tuberculosis cytochrome P450 CYP121A1, were prepared and evaluated for binding affinity and inhibitory activity (MIC) against M. tuberculosis. Series A replaces one phenol group of cYY with a C3-imidazole moiety, series B includes a keto group on the hydrocarbon chain preceding the series A imidazole, whilst series C explores replacing the keto group of the piperidone ring of cYY with a CH2-imidazole or CH2-triazole moiety to enhance binding interaction with the heme of CYP121A1. The series displayed moderate to weak type II binding affinity for CYP121A1, with the exception of series B 10a, which displayed mixed type I binding. Of the three series, series C imidazole derivatives showed the best, although modest, inhibitory activity against M. tuberculosis (17d MIC = 12.5 μg/mL, 17a 50 μg/mL). Crystal structures were determined for CYP121A1 bound to series A compounds 6a and 6b that show the imidazole groups positioned directly above the haem iron with binding between the haem iron and imidazole nitrogen of both compounds at a distance of 2.2 Å. A model generated from a 1.5 Å crystal structure of CYP121A1 in complex with compound 10a showed different binding modes in agreement with the heterogeneous binding observed. Although the crystal structures of 6a and 6b would indicate binding with CYP121A1, the binding assays themselves did not allow confirmation of CYP121A1 as the target
Patterns in Open String Field Theory Solutions
In open string field theory the kinetic operator mixes matter and ghost
sectors, and thus the ghost structure of classical solutions is not universal.
Nevertheless, we have found from numerical analysis that certain ratios of
expectation values for states involving pure ghost excitations appear to be
universal. We give an analytic expression for these ratios and find good
evidence that they are common to all known solutions of open string field
theory, including the tachyon vacuum solution, lump solutions and string fields
representing marginal deformations. We also draw attention to a close
correspondence between the expectation values for the pure matter components in
the tachyon vacuum solution and those in the solution of a simpler equation for
a ghost number zero string field. Finally we observe that the action of L_0 on
the tachyon condensate gives a state that is approximately factorized into a
matter and a ghost part.Comment: 21 pages, LaTe
Cell-Envelope Remodeling as a Determinant of Phenotypic Antibacterial Tolerance in Mycobacterium tuberculosis
[Image: see text] The mechanisms that lead to phenotypic antibacterial tolerance in bacteria remain poorly understood. We investigate whether changes in NaCl concentration toward physiologically higher values affect antibacterial efficacy against Mycobacterium tuberculosis (Mtb), the causal agent of human tuberculosis. Indeed, multiclass phenotypic antibacterial tolerance is observed during Mtb growth in physiologic saline. This includes changes in sensitivity to ethionamide, ethambutol, d-cycloserine, several aminoglycosides, and quinolones. By employing organism-wide metabolomic and lipidomic approaches combined with phenotypic tests, we identified a time-dependent biphasic adaptive response after exposure of Mtb to physiological levels of NaCl. A first rapid, extensive, and reversible phase was associated with changes in core and amino acid metabolism. In a second phase, Mtb responded with a substantial remodelling of plasma membrane and outer lipid membrane composition. We demonstrate that phenotypic tolerance at physiological concentrations of NaCl is the result of changes in plasma and outer membrane lipid remodeling and not changes in core metabolism. Altogether, these results indicate that physiologic saline-induced antibacterial tolerance is kinetically coupled to cell envelope changes and demonstrate that metabolic changes and growth arrest are not the cause of phenotypic tolerance observed in Mtb exposed to physiologic concentrations of NaCl. Importantly, this work uncovers a role for bacterial cell envelope remodeling in antibacterial tolerance, alongside well-documented allterations in respiration, metabolism, and growth rate
Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.
The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development.MEK was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunction with the Cambridge Commonwealth Trust and Cambridge Overseas Trust. AGC and KJM were supported by grants from the BBSRC (Grant No: BB/I019669/1 and BB/I019227/1). GGJ received funding from the Ogden Trust and the Isaac Newton Trust administered through the University of Cambridge Bursary Scheme. DSCH was supported by a Croucher Cambridge International Scholarship awarded in conjunction between the Croucher Foundation and the Cambridge Overseas Trust. SAH was supported by an Oliphant Cambridge Australia Scholarship (App No: 10132070) awarded by the Cambridge Commonwealth Trust. The contributions of LBM and LPSC were supported by funds from the Francis Crick Institute, which receives its core funding principally from Wellcome Trust, Cancer Research UK, and the UK Medical Research Council (to LPSC - MC_UP_A253_1111) and funds from FAPESP, CNPq and CAPES-PDSE (to LBM - 2011/21232-1, 140079/2013-0, 99999.003125/2014-09).This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.6b0000
Bioactivity of pyridine-2-thiolato-1-oxide metal complexes: Bi(III), Fe(III) and Ga(III) complexes as potent anti-Mycobacterium tuberculosis prospective agents
In the search for new therapeutic tools against tuberculosis and to further address the therapeutic potential of pyridine-2-thiol 1-oxide (Hmpo) metal complexes, two new octahedral [M(III)(mpo)3] complexes, with M = Ga or Bi, were synthesized and characterized in the solid state and in solution. Attempts to crystallize [Ga(III)(mpo)3] in CH2Cl2 led to single crystals of the reaction product [GaCl(mpo)2], where the gallium(III) ion is in a square basis pyramidal environment, trans-coordinated at the basis to two pyridine-2-thiolato 1-oxide anions acting as bidentate ligands through their oxygen and sulfur atoms. The biological activity of the new [M(III)(mpo)3] complexes together with that of the previously reported Fe(III) analogous compound and the pyridine-2-thiol 1-oxide sodium salt (Na mpo) was evaluated on Mycobacterium tuberculosis. The compounds showed excellent activity, both in the standard strain H37Rv ATCC 27294 (pan-susceptible) and in five clinical isolates that are resistant to the standard first-line anti-tuberculosis drugs isoniazid and rifampicin. These pyridine-2-thiol 1-oxide derivatives are promising compounds for the treatment of resistant tuberculosis.Instituto de Física La Plat
Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV
We search for the standard model Higgs boson produced in association with an
electroweak vector boson in events with no identified charged leptons, large
imbalance in transverse momentum, and two jets where at least one contains a
secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1
integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV
recorded by the CDF II experiment at the Tevatron. We find 268 (16) single
(double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are
expected from standard model background processes. We place 95% confidence
level upper limits on the Higgs boson production cross section for several
Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115
GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model
prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let
Observation and Mass Measurement of the Baryon
We report the observation and measurement of the mass of the bottom, strange
baryon through the decay chain , where
, , and .
Evidence for observation is based on a signal whose probability of arising from
the estimated background is 6.6 x 10^{-15}, or 7.7 Gaussian standard
deviations. The mass is measured to be (stat.) (syst.) MeV/.Comment: Minor text changes for the second version. Accepted by Phys. Rev.
Let
Polarizations of J/psi and psi(2S) Mesons Produced in ppbar Collisions at 1.96 TeV
We have measured the polarizations of \jpsi and \psiprime mesons as
functions of their transverse momentum \pt when they are produced promptly in
the rapidity range with \pt \geq 5 \pgev. The analysis is performed
using a data sample with an integrated luminosity of about 800 \ipb collected
by the CDF II detector. For both vector mesons, we find that the polarizations
become increasingly longitudinal as \pt increases from 5 to 30 \pgev. These
results are compared to the predictions of nonrelativistic quantum
chromodynamics and other contemporary models. The effective polarizations of
\jpsi and \psiprime mesons from -hadron decays are also reported.Comment: 8 pages, 7 figures, published in Physical Review Letter
- …