1,548 research outputs found
Experimental Evolution of Resistance to Artemisinin Combination Therapy Results in Amplification of the mdr1 Gene in a Rodent Malaria Parasite
Background: Lacking suitable alternatives, the control of malaria increasingly depends upon Artemisinin Combination Treatments (ACT): resistance to these drugs would therefore be disastrous. For ACTs, the biology of resistance to the individual components has been investigated, but experimentally induced resistance to component drugs in combination has not been generated. Methodology/Principal Findings: We have used the rodent malaria parasite Plasmodium chabaudi to select in vivo resistance to the artesunate (ATN) + mefloquine (MF) version of ACT, through prolonged exposure of parasites to both drugs over many generations. The selection procedure was carried out over twenty-seven consecutive sub-inoculations under increasing ATN + MF doses, after which a genetically stable resistant parasite, AS-ATNMF1, was cloned. AS-ATNMF1 showed increased resistance to ATN + MF treatment and to artesunate or mefloquine administered separately. Investigation of candidate genes revealed an mdr1 duplication in the resistant parasites and increased levels of mdr1 transcripts and protein. There were no point mutations in the atpase6 or ubp1genes. Conclusion: Resistance to ACTs may evolve even when the two drugs within the combination are taken simultaneously and amplification of the mdr1 gene may contribute to this phenotype. However, we propose that other gene(s), as ye
Testing Nelder-Mead based repulsion algorithms for multiple roots of nonlinear systems via a two-level factorial design of experiments
This paper addresses the challenging task of computing multiple roots of a system of nonlinear equations. A repulsion algorithm that invokes the Nelder-Mead (N-M) local search method and uses a penalty-type merit function based on the error function, known as 'erf', is presented. In the N-M algorithm context, different strategies are proposed to enhance the quality of the solutions and improve the overall efficiency. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm.Fundação para a Ciência e Tecnologia (FCT
fabH deletion increases DHA productionin Escherichia coli expressing Pfa genes
Background: Some marine bacteria, such as Moritella marina, produce the nutraceutical docosahexaenoic acid (DHA) thanks to a specific enzymatic complex called Pfa synthase. Escherichia coli heterologously expressing the pfa gene cluster from M. marina also produces DHA. The aim of this study was to find genetic or metabolic conditions to increase DHA production in E. coli. Results: First, we analysed the effect of the antibiotic cerulenin, showing that DHA production increased twofold. Then, we tested a series of single gene knockout mutations affecting fatty acid biosynthesis, in order to optimize the synthesis of DHA. The most effective mutant, fabH, showed a threefold increase compared to wild type strain. The combination of cerulenin inhibition and fabH deletion rendered a 6.5-fold improvement compared to control strain. Both strategies seem to have the same mechanism of action, in which fatty acid synthesis via the canonical pathway (fab pathway) is affected in its first catalytic step, which allows the substrates to be used by the heterologous pathway to synthesize DHA. Conclusions: DHA-producing E. coli strain that carries a fabH gene deletion boosts DHA production by tuning down the competing canonical biosynthesis pathway. Our approach can be used for optimization of DHA production in different organisms.Funding: The work in the FdlC and GM laboratories was financed by the Spanish Ministry of Economy, Industry and Competitiveness Grant BFU2014-55534-C2
Observation of an Exotic Baryon in Exclusive Photoproduction from the Deuteron
In an exclusive measurement of the reaction , a
narrow peak that can be attributed to an exotic baryon with strangeness
is seen in the invariant mass spectrum. The peak is at
GeV/c with a measured width of 0.021 GeV/c FWHM, which is largely
determined by experimental mass resolution. The statistical significance of the
peak is . The mass and width of the observed peak are
consistent with recent reports of a narrow baryon by other experimental
groups.Comment: 5 pages, 5 figure
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n
We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic
range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c)
peaks where two nucleons each have 20% or less, and the third nucleon has most
of the transferred energy. These fast pp and pn pairs are back-to-back with
little momentum along the three-momentum transfer, indicating that they are
spectators. Experimental and theoretical evidence indicates that we have
measured distorted two-nucleon momentum distributions by striking the third
nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR
Search for the pentaquark in the reaction
A search for the \thp in the reaction was completed
using the CLAS detector at Jefferson Lab. A study of the same reaction,
published earlier, reported the observation of a narrow \thp resonance. The
present experiment, with more than 30 times the integrated luminosity of our
earlier measurement, does not show any evidence for a narrow pentaquark
resonance. The angle-integrated upper limit on \thp production in the mass
range of 1.52 to 1.56 GeV/c for the reaction is
0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and
angular distribution of \thp production. Using \lamstar production as an
empirical measure of rescattering in the deuteron, the cross section upper
limit for the elementary reaction is estimated to be
a factor of 10 higher, {\it i.e.}, nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment
Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12
Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using
2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12
targets in the CLAS detector. A_LT' is related to the imaginary part of the
longitudinal-transverse interference and in quasifree nucleon knockout it
provides an unambiguous signature for final state interactions (FSI).
Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3%
for data with good statistical precision. Optical Model in Eikonal
Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation
(RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure
Onset of asymptotic scaling in deuteron photodisintegration
We investigate the transition from the nucleon-meson to quark-gluon
description of the strong interaction using the photon energy dependence of the
differential cross section for photon energies above 0.5 GeV and
center-of-mass proton angles between and . A possible
signature for this transition is the onset of cross section scaling
with the total energy squared, , at some proton transverse momentum, .
The results show that the scaling has been reached for proton transverse
momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime
is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure
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