111 research outputs found
Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans
With the problem of parasitic nematode drug resistance increasing, vaccine development offers an alternative sustainable control approach. For some parasitic nematodes, native extracts enriched for specific proteins are highly protective. However, recombinant forms of these proteins have failed to replicate this protection. This is thought to be due to differences in glycosylation and/or conformation between native and recombinant proteins. We have exploited the free-living nematode Caenorhabditis elegans to examine its suitability as an alternative system for recombinant expression of parasitic nematode vaccine candidates. We focussed on Haemonchus contortus aminopeptidase H11 glycoprotein, which is enriched in a gut membrane fraction capable of inducing significant protection against this important ovine gastrointestinal nematode. We show that H. contortus H11 expressed in C. elegans is enzymatically active and MALDI mass spectrometry identifies similar di- and tri-fucosylated structures to those on native H11, with fucose at the 3- and/or 6-positions of the proximal GlcNAc. Some glycan structural differences were observed, such as lack of LDNF. Serum antibody to native H11 binds to C. elegans recombinant H11 and most of the antibody to rH11 or native H11 is directed to glycan moieties. Despite these similarities, no reduction in worm burden or faecal egg count was observed following immunisation of sheep with C. elegans-expressed recombinant H11 protein. The findings suggest that the di- and tri-fucosylated N-glycans expressed on rH11 do not contribute to the protective effect of H11 and that additional components present in native H11-enriched extract are likely required for enhancing the antibody response necessary for protection
The Primordial Inflation Explorer (PIXIE): A Nulling Polarimeter for Cosmic Microwave Background Observations
The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission to
measure the gravity-wave signature of primordial inflation through its
distinctive imprint on the linear polarization of the cosmic microwave
background. The instrument consists of a polarizing Michelson interferometer
configured as a nulling polarimeter to measure the difference spectrum between
orthogonal linear polarizations from two co-aligned beams. Either input can
view the sky or a temperature-controlled absolute reference blackbody
calibrator. PIXIE will map the absolute intensity and linear polarization
(Stokes I, Q, and U parameters) over the full sky in 400 spectral channels
spanning 2.5 decades in frequency from 30 GHz to 6 THz (1 cm to 50 um
wavelength). Multi-moded optics provide background-limited sensitivity using
only 4 detectors, while the highly symmetric design and multiple signal
modulations provide robust rejection of potential systematic errors. The
principal science goal is the detection and characterization of linear
polarization from an inflationary epoch in the early universe, with
tensor-to-scalar ratio r < 10^{-3} at 5 standard deviations. The rich PIXIE
data set will also constrain physical processes ranging from Big Bang cosmology
to the nature of the first stars to physical conditions within the interstellar
medium of the Galaxy.Comment: 37 pages including 17 figures. Submitted to the Journal of Cosmology
and Astroparticle Physic
CMB polarization from secondary vector and tensor modes
We consider a novel contribution to the polarization of the Cosmic Microwave
Background induced by vector and tensor modes generated by the non-linear
evolution of primordial scalar perturbations. Our calculation is based on
relativistic second-order perturbation theory and allows to estimate the
effects of these secondary modes on the polarization angular power-spectra. We
show that a non-vanishing B-mode polarization unavoidably arises from pure
scalar initial perturbations, thus limiting our ability to detect the signature
of primordial gravitational waves generated during inflation. This secondary
effect dominates over that of primordial tensors for an inflationary
tensor-to-scalar ratio . The magnitude of the effect is smaller than
the contamination produced by the conversion of polarization of type E into
type B, by weak gravitational lensing. However the lensing signal can be
cleaned, making the secondary modes discussed here the actual background
limiting the detection of small amplitude primordial gravitational waves.Comment: 14 pages, 3 figures, minor changes matching the version to be
published in Phys. Rev.
Limits on the gravity wave contribution to microwave anisotropies
We present limits on the fraction of large angle microwave anisotropies which
could come from tensor perturbations. We use the COBE results as well as
smaller scale CMB observations, measurements of galaxy correlations, abundances
of galaxy clusters, and Lyman alpha absorption cloud statistics. Our aim is to
provide conservative limits on the tensor-to-scalar ratio for standard
inflationary models. For power-law inflation, for example, we find T/S<0.52 at
95% confidence, with a similar constraint for phi^p potentials. However, for
models with tensor amplitude unrelated to the scalar spectral index it is still
currently possible to have T/S>1.Comment: 23 pages, 7 figures, accepted for publication in Phys. Rev. D.
Calculations extended to blue spectral index, Fig. 6 added, discussion of
results expande
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
Measurement of and charged current inclusive cross sections and their ratio with the T2K off-axis near detector
We report a measurement of cross section and the first measurements of the cross section
and their ratio
at (anti-)neutrino energies below 1.5
GeV. We determine the single momentum bin cross section measurements, averaged
over the T2K -flux, for the detector target material (mainly
Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory
frame kinematics of 500 MeV/c. The
results are and $\sigma(\nu)=\left( 2.41\
\pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}^{2}R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)=
0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure
Cosmological parameters from CMB and other data: a Monte-Carlo approach
We present a fast Markov Chain Monte-Carlo exploration of cosmological
parameter space. We perform a joint analysis of results from recent CMB
experiments and provide parameter constraints, including sigma_8, from the CMB
independent of other data. We next combine data from the CMB, HST Key Project,
2dF galaxy redshift survey, supernovae Ia and big-bang nucleosynthesis. The
Monte Carlo method allows the rapid investigation of a large number of
parameters, and we present results from 6 and 9 parameter analyses of flat
models, and an 11 parameter analysis of non-flat models. Our results include
constraints on the neutrino mass (m_nu < 0.3eV), equation of state of the dark
energy, and the tensor amplitude, as well as demonstrating the effect of
additional parameters on the base parameter constraints. In a series of
appendices we describe the many uses of importance sampling, including
computing results from new data and accuracy correction of results generated
from an approximate method. We also discuss the different ways of converting
parameter samples to parameter constraints, the effect of the prior, assess the
goodness of fit and consistency, and describe the use of analytic
marginalization over normalization parameters.Comment: Quintessence results now include perturbations. Changes to match
version accepted by PRD. MCMC code and data are available at
http://cosmologist.info/cosmomc/ along with a B&W printer-friendly version of
the pape
Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish
The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from C-14-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from C-14-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from C-14-acid lactic, while STC1-A increased gluconeogenesis from C-14-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil; Foundation for Science and Technology of Portugal [PTDC/MAR/121279/2010]; bilateral programme CAPES (Brazil)/GRICES (Portugal) CAPES/GRICES [215/08]info:eu-repo/semantics/publishedVersio
Probing Dark Energy with Supernovae: Exploiting Complementarity with the Cosmic Microwave Background
A primary goal for cosmology and particle physics over the coming decade will
be to unravel the nature of the dark energy that drives the accelerated
expansion of the Universe. In particular, determination of the
equation-of-state of dark energy, w equivalent p/rho, and its time variation,
dw/dz, will be critical for developing theoretical understanding of the new
physics behind this phenomenon. Type Ia supernovae (SNe) and cosmic microwave
background (CMB) anisotropy are each sensitive to the dark energy
equation-of-state. SNe alone can determine w(z) with some precision, while CMB
anisotropy alone cannot because of a strong degeneracy between the matter
density Omega_M and w. However, we show that the Planck CMB mission can
significantly improve the power of a deep SNe survey to probe w and especially
dw/dz. Because CMB constraints are nearly orthogonal to SNe constraints in the
Omega_M-w plane, for constraining w(z) Planck is more useful than precise
determination of Omega_M. We discuss how the CMB/SNe complementarity impacts
strategies for the redshift distribution of a supernova survey to determine
w(z) and conclude that a well-designed sample should include a substantial
number of supernovae out to redshifts z ~ 2.Comment: More discussion of CMB systematics and many new references added.
Matches the PRD versio
Primordial power spectrum from WMAP
The observed angular power spectrum of the cosmic microwave background
temperature anisotropy, , is a convolution of a cosmological radiative
transport kernel with an assumed primordial power spectrum of inhomogeneities.
Exquisite measurements of over a wide range of multipoles from the
Wilkinson Microwave Anisotropy Probe (WMAP) has opened up the possibility to
deconvolve the primordial power spectrum for a given set of cosmological
parameters (base model). We implement an improved (error sensitive)
Richardson-Lucy deconvolution algorithm on the measured angular power spectrum
from WMAP assuming a concordance cosmological model. The most prominent feature
of the recovered is a sharp, infra-red cut off on the horizon scale. The
resultant spectrum using the recovered spectrum has a likelihood far
better than a scale invariant, or, `best fit' scale free spectra
( {\it w.r.t.} Harrison Zeldovich, and, {\it w.r.t.} power law with ). The recovered has a
localized excess just below the cut-off which leads to great improvement of
likelihood over the simple monotonic forms of model infra-red cut-off spectra
considered in the post WMAP literature. The recovered , in particular,
the form of infra-red cut-off is robust to small changes in the cosmological
parameters. We show that remarkably similar form of infra-red cutoff is known
to arise in very reasonable extensions and refinements of the predictions from
simple inflationary scenarios. Our method can be extended to other cosmological
observations such as the measured matter power spectrum and, in particular, the
much awaited polarization spectrum from WMAP.Comment: 20 pages, 12 figures, uses Revtex4, Matches version accepted to Phys.
Rev. D. More extensive discussion of the method in the appendix, references
added and typos correcte
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