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 $r<10^{-6}$. 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 νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.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, $C_l$, is a convolution of a cosmological radiative transport kernel with an assumed primordial power spectrum of inhomogeneities. Exquisite measurements of $C_l$ 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 $P(k)$ is a sharp, infra-red cut off on the horizon scale. The resultant $C_l$ spectrum using the recovered spectrum has a likelihood far better than a scale invariant, or, `best fit' scale free spectra ($\Delta\ln{\cal L}=25$ {\it w.r.t.} Harrison Zeldovich, and, $\Delta\ln{\cal L}=11$ {\it w.r.t.} power law with $n_s=0.95$). The recovered $P(k)$ 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 $P(k)$, 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