802 research outputs found
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Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model
Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release
Patient-friendly integrated first trimester screening by NIPT and fetal anomaly scan
Many major structural fetal anomalies can be diagnosed by first trimester fetal anomaly scan. NIPT can accurately detect aneuploidies and large chromosomal aberrations in cfDNA in maternal blood plasma. This study shows how a patient-friendly first trimester screening for both chromosomal and structural fetal anomalies in only two outpatient visits can be provided. Genotype-first approach assures not only the earliest diagnosis of trisomy 21 (the most prevalent chromosome aberration), but also completion of the screening at 12â14Â weeks. To ensure proper management and avoid unnecessary anxiety abnormal NIPT different from trisomy 21, 18 and 13 should be referred for genetic counseling
New data on the ichthyosaur Platypterygius hercynicus and its implications for the validity of the genus
The description of a nearly complete skull from the late Albian of northwestern France
reveals previously unknown anatomical features of Platypterygius hercynicus (Kuhn 1946),
and of European Cretaceous ichthyosaurs in general. These include a wide frontal forming the
anteromedial border of the supratemporal fenestra, a parietal excluded from the parietal
foramen, and the likely presence of a squamosal, inferred from a very large and deep facet on
the quadratojugal. The absence of a squamosal has been considered as an autapomorphy of
the genus Platypterygius for more than ten years and has been applied to all known species by
default, but the described specimen casts doubt on this putative autapomorphy. Actually, it is
shown that all characters that have been proposed previously as autapomorphic for the genus
Platypterygius are either not found in all the species currently referred to this genus, or are
also present in other Ophthalmosauridae. Consequently, the genus Platypterygius must be
completely revised.Peer reviewe
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A laminated polymer film formulation for enteric delivery of live vaccine and probiotic bacteria
Live bacterial cells (LBC) are administered orally as attenuated vaccines, to deliver biopharmaceutical agents, and as probiotics to improve gastrointestinal health. However, LBC present unique formulation challenges and must survive gastrointestinal antimicrobial defenses including gastric acid after administration. We present a simple new formulation concept, termed Polymer Film Laminate (PFL). LBC are ambient dried onto cast acid-resistant enteric polymer films that are then laminated together to produce a solid oral dosage form. LBC of a model live bacterial vaccine and a probiotic were dried directly onto a cast film of enteric polymer. The effectiveness at protecting dried cells in a simulated gastric fluid (pH 2.0) depended on the composition of enteric polymer film used, with a blend of ethylcellulose plus Eudragit L100 55 providing greater protection from acid than Eudragit alone. However, although PFL made from blended polymers films completely released low molecular weight dye into intestinal conditions (pH 7.0), they failed to release LBC. In contrast, PFL made from Eudragit alone successfully protected dried probiotic or vaccine LBC from simulated gastric fluid for 2h, and subsequently released all viable cells within 60min of transfer into simulated intestinal fluid. Release kinetics could be controlled by modifying the lamination method
Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope
Nearby clusters and groups of galaxies are potentially bright sources of
high-energy gamma-ray emission resulting from the pair-annihilation of dark
matter particles. However, no significant gamma-ray emission has been detected
so far from clusters in the first 11 months of observations with the Fermi
Large Area Telescope. We interpret this non-detection in terms of constraints
on dark matter particle properties. In particular for leptonic annihilation
final states and particle masses greater than ~200 GeV, gamma-ray emission from
inverse Compton scattering of CMB photons is expected to dominate the dark
matter annihilation signal from clusters, and our gamma-ray limits exclude
large regions of the parameter space that would give a good fit to the recent
anomalous Pamela and Fermi-LAT electron-positron measurements. We also present
constraints on the annihilation of more standard dark matter candidates, such
as the lightest neutralino of supersymmetric models. The constraints are
particularly strong when including the fact that clusters are known to contain
substructure at least on galaxy scales, increasing the expected gamma-ray flux
by a factor of ~5 over a smooth-halo assumption. We also explore the effect of
uncertainties in cluster dark matter density profiles, finding a systematic
uncertainty in the constraints of roughly a factor of two, but similar overall
conclusions. In this work, we focus on deriving limits on dark matter models; a
more general consideration of the Fermi-LAT data on clusters and clusters as
gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo,
minor revisions to be consistent with accepted versio
Modification of alumina matrices through chemical etching and electroless deposition of nano-Au array for amperometric sensing
Simple nanoporous alumina matrix modification procedure, in which the electrically highly insulating alumina barrier layer at the bottom of the pores is replaced with the conductive layer of the gold beds, was described. This modification makes possible the direct electron exchange between the underlying aluminum support and the redox species encapsulated in the alumina pores, thus, providing the generic platform for the nanoporous alumina sensors (biosensors) with the direct amperometric signal readout fabrication
An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics
For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV
A search for pair-production of supersymmetric particles under the assumption
that R-parity is violated via a dominant LQDbar coupling has been performed
using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV.
The observed candidate events in the data are in agreement with the Standard
Model expectation. This result is translated into lower limits on the masses of
charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for
m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81
GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the
95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure
Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS
We present the results of a search for new, heavy particles that decay at a
significant distance from their production point into a final state containing
charged hadrons in association with a high-momentum muon. The search is
conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV
and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS
detector operating at the Large Hadron Collider. Production of such particles
is expected in various scenarios of physics beyond the standard model. We
observe no signal and place limits on the production cross-section of
supersymmetric particles in an R-parity-violating scenario as a function of the
neutralino lifetime. Limits are presented for different squark and neutralino
masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final
version to appear in Physics Letters
Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment
This paper describes an analysis of the angular distribution of W->enu and
W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with
the ATLAS detector at the LHC in 2010, corresponding to an integrated
luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and
the missing transverse energy, the W decay angular distribution projected onto
the transverse plane is obtained and analysed in terms of helicity fractions
f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV
and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw
> 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour,
are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017
+/- 0.030, where the first uncertainties are statistical, and the second
include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables,
revised author list, matches European Journal of Physics C versio
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