6,297 research outputs found
Metallochaperones Are Needed for Mycobacterium tuberculosis and Escherichia coli Nicotinamidase-Pyrazinamidase Activity.
Mycobacterium tuberculosis nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. M. tuberculosis and Escherichia coli PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo). Reactivation with the E. coli metallochaperone ZnuA or Rv2059 (the M. tuberculosis analog) was measured. This was repeated following proteolytic and thermal treatment of ZnuA and Rv2059. The CDC1551 M. tuberculosis reference strain had the Rv2059 coding gene knocked out, and PZA susceptibility and the pyrazinoic acid (POA) efflux rate were measured. ZnuA (200 μM) achieved 65% PZAse-EC-Apo reactivation. Rv2059 (1 μM) and ZnuA (1 μM) achieved 69% and 34.3% PZAse-MT-Apo reactivation, respectively. Proteolytic treatment of ZnuA and Rv2059 and application of three (but not one) thermal shocks to ZnuA significantly reduced the capacity to reactivate PZAse-MT-Apo. An M. tuberculosis Rv2059 knockout strain was Wayne positive and susceptible to PZA and did not have a significantly different POA efflux rate than the reference strain, although a trend toward a lower efflux rate was observed after knockout. The metallochaperone Rv2059 restored the activity of metal-depleted PZAse in vitro Although Rv2059 is important in vitro, it seems to have a smaller effect on PZA susceptibility in vivo. It may be important to mechanisms of action and resistance to pyrazinamide in M. tuberculosis Further studies are needed for confirmation.IMPORTANCE Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis and remains one of the major causes of disease and death worldwide. Pyrazinamide is a key drug used in the treatment of tuberculosis, yet its mechanism of action is not fully understood, and testing strains of M. tuberculosis for pyrazinamide resistance is not easy with the tools that are presently available. The significance of the present research is that a metallochaperone-like protein may be crucial to pyrazinamide's mechanisms of action and of resistance. This may support the development of improved tools to detect pyrazinamide resistance, which would have significant implications for the clinical management of patients with tuberculosis: drug regimens that are appropriately tailored to the resistance profile of a patient's individual strain lead to better clinical outcomes, reduced onward transmission of infection, and reduction of the development of resistant strains that are more challenging and expensive to treat
Numerical study of resistivity of model disordered three-dimensional metals
We calculate the zero-temperature resistivity of model 3-dimensional
disordered metals described by tight-binding Hamiltonians. Two different
mechanisms of disorder are considered: diagonal and off-diagonal. The
non-equilibrium Green function formalism provides a Landauer-type formula for
the conductance of arbitrary mesoscopic systems. We use this formula to
calculate the resistance of finite-size disordered samples of different
lengths. The resistance averaged over disorder configurations is linear in
sample length and resistivity is found from the coefficient of proportionality.
Two structures are considered: (1) a simple cubic lattice with one s-orbital
per site, (2) a simple cubic lattice with two d-orbitals. For small values of
the disorder strength, our results agree with those obtained from the Boltzmann
equation. Large off-diagonal disorder causes the resistivity to saturate,
whereas increasing diagonal disorder causes the resistivity to increase faster
than the Boltzmann result. The crossover toward localization starts when the
Boltzmann mean free path relative to the lattice constant has a value between
0.5 and 2.0 and is strongly model dependent.Comment: 4 pages, 5 figure
decays
Effective chiral theory of mesons is applied to study the four decay modes of
. Theoretical values of the branching ratios are in
agreement with the data. The theory predicts that the resonance plays a
dominant role in these decays. There is no new parameter in this study.Comment: 12 pages and one figur
Kinematic dynamo action in a sphere. I. Effects of differential rotation and meridional circulation on solutions with axial dipole symmetry
A sphere containing electrically conducting fluid can generate a magnetic field by dynamo action, provided the flow is sufficiently complicated and vigorous. The dynamo mechanism is thought to sustain magnetic fields in planets and stars. The kinematic dynamo problem tests steady flows for magnetic instability, but rather few dynamos have been found so far because of severe numerical difficulties. Dynamo action might, therefore, be quite unusual, at least for large-scale steady flows. We address this question by testing a two-parameter class of flows for dynamo generation of magnetic fields containing an axial dipole. The class of flows includes two completely different types of known dynamos, one dominated by differential rotation (D) and one with none. We find that 36% of the flows in seven distinct zones in parameter space act as dynamos, while the remaining 64% either fail to generate this type of magnetic field or generate fields that are too small in scale to be resolved by our numerical method. The two previously known dynamo types lie in the same zone, and it is therefore possible to change the flow continuously from one to the other without losing dynamo action. Differential rotation is found to promote large-scale axisymmetric toroidal magnetic fields, while meridional circulation (M) promotes large-scale axisymmetric poloidal fields concentrated at high latitudes near the axis. Magnetic fields resembling that of the Earth are generated by D > 0, corresponding to westward flow at the surface, and M of either sign but not zero. Very few oscillatory solutions are found
Magnetic confinement of the solar tachocline
We study the physics of the solar tachocline and related MHD instabilities.
We have performed 3-D MHD simulations of the solar radiative interior to check
whether a fossil magnetic field is able to prevent the spread of the
tachocline. Starting with a purely poloidal magnetic field and a latitudinal
shear meant to be imposed by the convection zone at the top of the radiation
zone, we have investigated the interactions between magnetic fields, rotation
and shear, using the spectral code ASH on massive parallel supercomputers. In
all cases we have explored, the fossil field diffuses outward and ends up
connecting with the convection zone, whose differential rotation is then
imprinted at latitudes above 40 deg throughout the radiative interior,
according to Ferraro's law of isorotation. Rotation remains uniform in the
lower latitude region which is contained within closed field lines. We find
that the meridional flow cannot stop the inward progression of the differential
rotation. Further, we observe the development of non-axisymmetric
magnetohydrodynamic instabilities, first due to the initial poloidal
configuration of the fossil field, and later to the toroidal field produced by
shearing the poloidal field through the differential rotation. We do not find
dynamo action as such in the radiative interior, since the mean poloidal field
is not regenerated. But the instability persists during the whole evolution,
while slowly decaying with the mean poloidal field. According to our numerical
simulations, a fossil magnetic field cannot prevent the radiative spread of the
tachocline, and thus it is unable to enforce uniform rotation in the radiation
zone. Neither can the observed thinness of that layer be invoked as a proof for
such an internal fossil magnetic field.Comment: 12 pages, 8 color figures (low res), published in A&A, october 200
System Advisor Model, SAM 2011.12.2: General Description
This document describes the capabilities of the U.S. Department of Energy and National Renewable Energy Laboratory's System Advisor Model (SAM), Version 2011.12.2, released on December 2, 2011. SAM is software that models the cost and performance of renewable energy systems. Project developers, policy makers, equipment manufacturers, and researchers use graphs and tables of SAM results in the process of evaluating financial, technology, and incentive options for renewable energy projects. SAM simulates the performance of solar, wind, geothermal, biomass, and conventional power systems. The financial model can represent financing structures for projects that either buy and sell electricity at retail rates (residential and commercial) or sell electricity at a price determined in a power purchase agreement (utility). Advanced analysis options facilitate parametric, sensitivity, and statistical analyses, and allow for interfacing SAM with Microsoft Excel or with other computer programs. SAM is available as a free download at http://sam.nrel.gov. Technical support and more information about the software are available on the website
Mechanisms of Addition and Substitution Reactions of Furfural and Derivatives
In a complete series of substitution reactions (such as halogenation, nitration, mercuration, etc.,) of furfural and its derivatives, it appears that substitution is preceded by addition. For example, in bromination, two atoms of bromine first add to give a relatively unstable intermediate which then loses hydrogen bromide. These preliminary additions may be 1, 2- or 1, 4- or 1, 6- additions depending upon reactants and upon experimental conditions. Accompanying some of these transformations are ring fission and ring closure, and rearrangements involving unsaturated linkages. Typical illustrations of these changes were presented
Amorphous Systems in Athermal, Quasistatic Shear
We present results on a series of 2D atomistic computer simulations of
amorphous systems subjected to simple shear in the athermal, quasistatic limit.
The athermal quasistatic trajectories are shown to separate into smooth,
reversible elastic branches which are intermittently broken by discrete
catastrophic plastic events. The onset of a typical plastic event is studied
with precision, and it is shown that the mode of the system which is
responsible for the loss of stability has structure in real space which is
consistent with a quadrupolar source acting on an elastic matrix. The plastic
events themselves are shown to be composed of localized shear transformations
which organize into lines of slip which span the length of the simulation cell,
and a mechanism for the organization is discussed. Although within a single
event there are strong spatial correlations in the deformation, we find little
correlation from one event to the next, and these transient lines of slip are
not to be confounded with the persistent regions of localized shear --
so-called "shear bands" -- found in related studies. The slip lines gives rise
to particular scalings with system length of various measures of event size.
Strikingly, data obtained using three differing interaction potentials can be
brought into quantitative agreement after a simple rescaling, emphasizing the
insensitivity of the emergent plastic behavior in these disordered systems to
the precise details of the underlying interactions. The results should be
relevant to understanding plastic deformation in systems such as metallic
glasses well below their glass temperature, soft glassy systems (such as dense
emulsions), or compressed granular materials.Comment: 21 pages, 18 figure
Transition between nuclear and quark-gluon descriptions of hadrons and light nuclei
We provide a perspective on studies aimed at observing the transition between
hadronic and quark-gluonic descriptions of reactions involving light nuclei. We
begin by summarizing the results for relatively simple reactions such as the
pion form factor and the neutral pion transition form factor as well as that
for the nucleon and end with exclusive photoreactions in our simplest nuclei. A
particular focus will be on reactions involving the deuteron. It is noted that
a firm understanding of these issues is essential for unraveling important
structure information from processes such as deeply virtual Compton scattering
as well as deeply virtual meson production. The connection to exotic phenomena
such as color transparency will be discussed. A number of outstanding
challenges will require new experiments at modern facilities on the horizon as
well as further theoretical developments.Comment: 37 pages, 17 figures, submitted to Reports on Progress in Physic
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