204 research outputs found
Aspergillus niger Protein EstA Defines a New Class of Fungal Esterases within the α/β Hydrolase Fold Superfamily of Proteins
AbstractFrom the fungus Aspergillus niger, we identified a new gene encoding protein EstA, a member of the α/β-hydrolase fold superfamily but of unknown substrate specificity. EstA was overexpressed and its crystal structure was solved by molecular replacement using a lipase-acetylcholinesterase chimera template. The 2.1 Å resolution structure of EstA reveals a canonical Ser/Glu/His catalytic triad located in a small pocket at the bottom of a large solvent-accessible, bowl-shaped cavity. Potential substrates selected by manual docking procedures were assayed for EstA activity. Consistent with the pocket geometry, preference for hydrolysis of short acyl/propyl chain substrates was found. Identification of close homologs from the genome of other fungi, of which some are broad host-range pathogens, defines EstA as the first member of a novel class of fungal esterases within the superfamily. Hence the structure of EstA constitutes a lead template in the design of new antifungal agents directed toward its pathogenic homologs
Self-tuning experience weighted attraction learning in games
Self-tuning experience weighted attraction (EWA) is a one-parameter theory of learning in
games. It addresses a criticism that an earlier model (EWA) has too many parameters, by
fixing some parameters at plausible values and replacing others with functions of experience
so that they no longer need to be estimated. Consequently, it is econometrically simpler
than the popular weighted fictitious play and reinforcement learning models.
The functions of experience which replace free parameters “self-tune” over time, adjusting
in a way that selects a sensible learning rule to capture subjects’ choice dynamics. For
instance, the self-tuning EWA model can turn from a weighted fictitious play into an averaging
reinforcement learning as subjects equilibrate and learn to ignore inferior foregone
payoffs. The theory was tested on seven different games, and compared to the earlier parametric
EWA model and a one-parameter stochastic equilibrium theory (QRE). Self-tuning
EWA does as well as EWA in predicting behavior in new games, even though it has fewer
parameters, and fits reliably better than the QRE equilibrium benchmark
The Atacama Cosmology Telescope: A Measurement of the 600< ell <8000 Cosmic Microwave Background Power Spectrum at 148 GHz
We present a measurement of the angular power spectrum of the cosmic
microwave background (CMB) radiation observed at 148 GHz. The measurement uses
maps with 1.4' angular resolution made with data from the Atacama Cosmology
Telescope (ACT). The observations cover 228 square degrees of the southern sky,
in a 4.2-degree-wide strip centered on declination 53 degrees South. The CMB at
arcminute angular scales is particularly sensitive to the Silk damping scale,
to the Sunyaev-Zel'dovich (SZ) effect from galaxy clusters, and to emission by
radio sources and dusty galaxies. After masking the 108 brightest point sources
in our maps, we estimate the power spectrum between 600 < \ell < 8000 using the
adaptive multi-taper method to minimize spectral leakage and maximize use of
the full data set. Our absolute calibration is based on observations of Uranus.
To verify the calibration and test the fidelity of our map at large angular
scales, we cross-correlate the ACT map to the WMAP map and recover the WMAP
power spectrum from 250 < ell < 1150. The power beyond the Silk damping tail of
the CMB is consistent with models of the emission from point sources. We
quantify the contribution of SZ clusters to the power spectrum by fitting to a
model normalized at sigma8 = 0.8. We constrain the model's amplitude ASZ < 1.63
(95% CL). If interpreted as a measurement of sigma8, this implies sigma8^SZ <
0.86 (95% CL) given our SZ model. A fit of ACT and WMAP five-year data jointly
to a 6-parameter LCDM model plus terms for point sources and the SZ effect is
consistent with these results.Comment: 15 pages, 8 figures. Accepted for publication in Ap
N-WASP control of LPAR1 trafficking establishes response to self-generated LPA gradients to promote pancreatic cancer cell metastasis
Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells. Pancreatic cancer cells break lysophosphatidic acid down as they respond to it, setting up a self-generated gradient driving tumor egress. N-WASP-depleted cells do not recognize lysophosphatidic acid gradients, leading to altered RhoA activation, decreased contractility and traction forces, and reduced metastasis. We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread
The Atacama Cosmology Telescope (ACT): Beam Profiles and First SZ Cluster Maps
The Atacama Cosmology Telescope (ACT) is currently observing the cosmic
microwave background with arcminute resolution at 148 GHz, 218 GHz, and 277
GHz. In this paper, we present ACT's first results. Data have been analyzed
using a maximum-likelihood map-making method which uses B-splines to model and
remove the atmospheric signal. It has been used to make high-precision beam
maps from which we determine the experiment's window functions. This beam
information directly impacts all subsequent analyses of the data. We also used
the method to map a sample of galaxy clusters via the Sunyaev-Zel'dovich (SZ)
effect, and show five clusters previously detected with X-ray or SZ
observations. We provide integrated Compton-y measurements for each cluster. Of
particular interest is our detection of the z = 0.44 component of A3128 and our
current non-detection of the low-redshift part, providing strong evidence that
the further cluster is more massive as suggested by X-ray measurements. This is
a compelling example of the redshift-independent mass selection of the SZ
effect.Comment: 16 pages, 10 figures. Accepted for publication in ApJS. See Marriage
et al. (arXiv:1010.1065) and Menanteau et al. (arXiv:1006.5126) for
additional cluster result
The Atacama Cosmology Telescope: Cosmological Parameters from the 2008 Power Spectra
We present cosmological parameters derived from the angular power spectrum of
the cosmic microwave background (CMB) radiation observed at 148 GHz and 218 GHz
over 296 deg^2 with the Atacama Cosmology Telescope (ACT) during its 2008
season. ACT measures fluctuations at scales 500<l<10000. We fit a model for the
lensed CMB, Sunyaev-Zel'dovich (SZ), and foreground contribution to the 148 GHz
and 218 GHz power spectra, including thermal and kinetic SZ, Poisson power from
radio and infrared point sources, and clustered power from infrared point
sources. The power from thermal and kinetic SZ at 148 GHz is estimated to be
B_3000 = 6.8+-2.9 uK^2, where B_l=l(l+1)C_l/2pi. We estimate primary
cosmological parameters from the 148 GHz spectrum, marginalizing over SZ and
source power. The LCDM cosmological model is a good fit to the data, and LCDM
parameters estimated from ACT+WMAP are consistent with the 7-year WMAP limits,
with scale invariant n_s = 1 excluded at 99.7% CL (3sigma). A model with no CMB
lensing is disfavored at 2.8sigma. By measuring the third to seventh acoustic
peaks, and probing the Silk damping regime, the ACT data improve limits on
cosmological parameters that affect the small-scale CMB power. The ACT data
combined with WMAP give a 6sigma detection of primordial helium, with Y_P =
0.313+-0.044, and a 4sigma detection of relativistic species, assumed to be
neutrinos, with Neff = 5.3+-1.3 (4.6+-0.8 with BAO+H0 data). From the CMB alone
the running of the spectral index is constrained to be dn/dlnk = -0.034 +-
0.018, the limit on the tensor-to-scalar ratio is r<0.25 (95% CL), and the
possible contribution of Nambu cosmic strings to the power spectrum is
constrained to string tension Gmu<1.6 \times 10^-7 (95% CL).Comment: 20 pages, 13 figures. Submitted to ApJ. This paper is a companion to
Hajian et al. (2010) and Das et al. (2010
The Atacama Cosmology Telescope: A Measurement of the Cosmic Microwave Background Power Spectrum at 148 and 218 GHz from the 2008 Southern Survey
We present measurements of the cosmic microwave background (CMB) power
spectrum made by the Atacama Cosmology Telescope at 148 GHz and 218 GHz, as
well as the cross-frequency spectrum between the two channels. Our results
clearly show the second through the seventh acoustic peaks in the CMB power
spectrum. The measurements of these higher-order peaks provide an additional
test of the {\Lambda}CDM cosmological model. At l > 3000, we detect power in
excess of the primary anisotropy spectrum of the CMB. At lower multipoles 500 <
l < 3000, we find evidence for gravitational lensing of the CMB in the power
spectrum at the 2.8{\sigma} level. We also detect a low level of Galactic dust
in our maps, which demonstrates that we can recover known faint, diffuse
signals.Comment: 19 pages, 13 figures. Submitted to ApJ. This paper is a companion to
Hajian et al. (2010) and Dunkley et al. (2010
The Atacama Cosmology Telescope: Data Characterization and Map Making
We present a description of the data reduction and mapmaking pipeline used
for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The
data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from
2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours
of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours
of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2
hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were
devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial
equator. We discuss sources of statistical and systematic noise, calibration,
telescope pointing, and data selection. Out of 1260 survey hours and 1024
detectors per array, 816 hours and 593 effective detectors remain after data
selection for this frequency band, yielding a 38% survey efficiency. The total
sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in
the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units.
Atmospheric brightness fluctuations constitute the main contaminant in the data
and dominate the detector noise covariance at low frequencies in the TOD. The
maps were made by solving the least-squares problem using the Preconditioned
Conjugate Gradient method, incorporating the details of the detector and noise
correlations. Cross-correlation with WMAP sky maps, as well as analysis from
simulations, reveal that our maps are unbiased at multipoles ell > 300. This
paper accompanies the public release of the 148 GHz southern stripe maps from
2008. The techniques described here will be applied to future maps and data
releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape
The Atacama Cosmology Telescope: Cosmology from Galaxy Clusters Detected via the Sunyaev-Zel'dovich Effect
We present constraints on cosmological parameters based on a sample of
Sunyaev-Zel'dovich-selected galaxy clusters detected in a millimeter-wave
survey by the Atacama Cosmology Telescope. The cluster sample used in this
analysis consists of 9 optically-confirmed high-mass clusters comprising the
high-significance end of the total cluster sample identified in 455 square
degrees of sky surveyed during 2008 at 148 GHz. We focus on the most massive
systems to reduce the degeneracy between unknown cluster astrophysics and
cosmology derived from SZ surveys. We describe the scaling relation between
cluster mass and SZ signal with a 4-parameter fit. Marginalizing over the
values of the parameters in this fit with conservative priors gives sigma_8 =
0.851 +/- 0.115 and w = -1.14 +/- 0.35 for a spatially-flat wCDM cosmological
model with WMAP 7-year priors on cosmological parameters. This gives a modest
improvement in statistical uncertainty over WMAP 7-year constraints alone.
Fixing the scaling relation between cluster mass and SZ signal to a fiducial
relation obtained from numerical simulations and calibrated by X-ray
observations, we find sigma_8 = 0.821 +/- 0.044 and w = -1.05 +/- 0.20. These
results are consistent with constraints from WMAP 7 plus baryon acoustic
oscillations plus type Ia supernoava which give sigma_8 = 0.802 +/- 0.038 and w
= -0.98 +/- 0.053. A stacking analysis of the clusters in this sample compared
to clusters simulated assuming the fiducial model also shows good agreement.
These results suggest that, given the sample of clusters used here, both the
astrophysics of massive clusters and the cosmological parameters derived from
them are broadly consistent with current models.Comment: 12 pages, 7 figures. Submitted to Ap
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