1,058 research outputs found
Transition States and Control of Substrate Preference in the Promiscuous Phosphatase PP1
Catalytically promiscuous enzymes are an attractive frontier for biochemistry, because enzyme promiscuities not only plausibly explain enzyme evolution through the mechanism of gene duplication but also could provide an efficient route to changing the catalytic function of proteins by mimicking this evolutionary process. PP1γ is an effectively promiscuous phosphatase for the hydrolysis of both monoanionic and dianionic phosphate ester-based substrates. In addition to its native phosphate monoester substrate, PP1γ catalyzes the hydrolysis of aryl methylphosphonates, fluorophosphate esters, phosphorothioate esters, and phosphodiesters, with second-order rate accelerations that fall within the narrow range of 10(11)-10(13). In contrast to the different transition states in the uncatalyzed hydrolysis reactions of these substrates, PP1γ catalyzes their hydrolysis through similar transition states. PP1γ does not catalyze the hydrolysis of a sulfate ester, which is unexpected. The PP1γ active site is tolerant of variations in the geometry of bound ligands, which permit the effective catalysis even of substrates whose steric requirements may result in perturbations to the positioning of the transferring group, both in the initial enzyme-substrate complex and in the transition state. The conservative mutation of arginine 221 to lysine results in a mutant that is a more effective catalyst toward monoanionic substrates. The surprising conversion of substrate preference lends support to the notion that mutations following gene duplication can result in an altered enzyme with different catalytic capabilities and preferences and may provide a pathway for the evolution of new enzymes
Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.
Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. Objectives The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. Methods This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. Results There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). Conclusions No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious
Twist Deformations of the Supersymmetric Quantum Mechanics
The N-extended Supersymmetric Quantum Mechanics is deformed via an abelian
twist which preserves the super-Hopf algebra structure of its Universal
Enveloping Superalgebra. Two constructions are possible. For even N one can
identify the 1D N-extended superalgebra with the fermionic Heisenberg algebra.
Alternatively, supersymmetry generators can be realized as operators belonging
to the Universal Enveloping Superalgebra of one bosonic and several fermionic
oscillators. The deformed system is described in terms of twisted operators
satisfying twist-deformed (anti)commutators. The main differences between an
abelian twist defined in terms of fermionic operators and an abelian twist
defined in terms of bosonic operators are discussed.Comment: 18 pages; two references adde
Synthesis effects on the magnetic and superconducting properties of RuSr2GdCu2O8
A systematic study on the synthesis of the Ru-1212 compound by preparing a
series of samples that were annealed at increasing temperatures and then
quenched has been performed. It results that the optimal temperature for the
annealing lies around 1060-1065 C; a further temperature increase worsens the
phase formation. Structural order is very important and the subsequent grinding
and annealing improves it. Even if from the structural point of view the
samples appear substantially similar, the physical characterization highlight
great differences both in the electrical and magnetic properties related to
intrinsic properties of the phase as well as to the connection between the
grains as inferred from the resistive and the Curie Weiss behaviour at high
temperature as well as in the visibility of ZFC anf FC magnetic signals.Comment: 17 pages, 12 figures. Proc. Int. Workshop " Ruthenate and
rutheno-cuprate materials: theory and experiments", Vietri, October 2001. To
be published on LNP Series, Springer Verlag, Berlin, C. Noce, A. Vecchione,
M. Cuoco, A. Romano Eds, 200
Coherent dynamics of Bose-Einstein condensates in high-finesse optical cavities
We study the mutual interaction of a Bose-Einstein condensed gas with a
single mode of a high-finesse optical cavity. We show how the cavity
transmission reflects condensate properties and calculate the self-consistent
intra-cavity light field and condensate evolution. Solving the coupled
condensate-cavity equations we find that while falling through the cavity, the
condensate is adiabatically transfered into the ground state of the periodic
optical potential. This allows time dependent non-destructive measurements on
Bose-Einstein condensates with intriguing prospects for subsequent controlled
manipulation.Comment: 5 pages, 5 figures; revised version: added reference
The Superconductivity, Intragrain Penetration Depth and Meissner Effect of RuSr2(Gd,Ce)2Cu2O10+delta
The hole concentration (p)(delta), the transition temperature Tc, the
intragrain penetration depth lambda, and the Meissner effect were measured for
annealed RuSr2(Gd,Ce)2Cu2O10+delta samples. The intragrain superconducting
transition temperature Tc} varied from 17 to 40 K while the p changed by only
0.03 holes/CuO2. The intragrain superfluid-density 1/lambda^2 and the
diamagnetic drop of the field-cooled magnetization across Tc (the Meissner
effect), however, increased more than 10 times. All of these findings are in
disagreement with both the Tc vs. p and the Tc vs. 1/lambda^2 correlations
proposed for homogeneous cuprates, but are in line with a possible
phase-separation and the granularity associated with it.Comment: 7 pages, 6 figures, accepted for publication in Phys. Rev. B (May 2,
2002
Superconducting properties of RuSr2GdCu2O8 studied by SQUID magnetometry
For polycrystalline RuSr2GdCu2O8 (Ru-1212), distinct peaks have been reported
in d.c. magnetization in the superconducting state of the sample. Sr2GdRuO6
(Sr-2116), the precursor for the preparation of Ru-1212, shows similar peaks in
the same temperature regime. Based on measurements performed on both bulk and
powdered samples of Ru-1212 and Sr-2116, we exclude the possibility, that the
observed behavior of the magnetization of Ru-1212 is due to Sr-2116 impurities.
The effect is related to the superconductivity of Ru-1212, but it is not an
intrinsic property of this compound. We provide evidence that the observation
of magnetization peaks in the superconducting state of Ru-1212 is due to flux
motion generated by the movement of the sample in an inhomogeneous field,
during the measurement in the SQUID magnetometer. We propose several tests,
that help to decide, whether the features observed in a SQUID magnetization
measurement of Ru-1212 represent a property of the compound or not.Comment: 22 pages, 9 figure
Recommended from our members
Quantum fluctuations of charge order induce phonon softening in a superconducting cuprate
Quantum phase transitions play an important role in shaping the phase diagram
of high-temperature cuprate superconductors. These cuprates possess intertwined
orders which interact strongly with superconductivity. However, the evidence
for the quantum critical point associated with the charge order in the
superconducting phase remains elusive. Here we show the short-range charge
orders and the spectral signature of the quantum fluctuations in
LaSrCuO (LSCO) near the optimal doping using high-resolution
resonant inelastic X-ray scattering. On performing calculations through a
diagrammatic framework, we discovered that the charge correlations
significantly soften several branches of phonons. These results elucidate the
role of charge order in the LSCO compound, providing evidence for quantum
critical scaling and discommensurations associated with charge order
Quantum fluctuations of charge order induce phonon softening in a superconducting cuprate
Quantum phase transitions play an important role in shaping the phase diagram
of high-temperature cuprate superconductors. These cuprates possess intertwined
orders which interact strongly with superconductivity. However, the evidence
for the quantum critical point associated with the charge order in the
superconducting phase remains elusive. Here we show the short-range charge
orders and the spectral signature of the quantum fluctuations in
LaSrCuO (LSCO) near the optimal doping using high-resolution
resonant inelastic X-ray scattering. On performing calculations through a
diagrammatic framework, we discovered that the charge correlations
significantly soften several branches of phonons. These results elucidate the
role of charge order in the LSCO compound, providing evidence for quantum
critical scaling and discommensurations associated with charge order
Cosmological parameters from SDSS and WMAP
We measure cosmological parameters using the three-dimensional power spectrum
P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in
combination with WMAP and other data. Our results are consistent with a
``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt,
tensor modes or massive neutrinos. Adding SDSS information more than halves the
WMAP-only error bars on some parameters, tightening 1 sigma constraints on the
Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter
density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on
neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when
dropping prior assumptions about curvature, neutrinos, tensor modes and the
equation of state. Our results are in substantial agreement with the joint
analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive
consistency check with independent redshift survey data and analysis
techniques. In this paper, we place particular emphasis on clarifying the
physical origin of the constraints, i.e., what we do and do not know when using
different data sets and prior assumptions. For instance, dropping the
assumption that space is perfectly flat, the WMAP-only constraint on the
measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to
t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running
tilt, neutrino mass and equation of state in the list of free parameters, many
constraints are still quite weak, but future cosmological measurements from
SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt
figures available at http://www.hep.upenn.edu/~max/sdsspars.htm
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