785 research outputs found
A novel non-mineral oil-based adjuvant. II. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in pigs
The adjuvanticity of a sulfolipopolysaccharide (SLP) incorporated into a squalane-in-water emulsion (SLP/S/W) was compared with that of a mineral oil-in-water (O/W) adjuvant currently used in commercial porcine vaccines. Groups of pigs were immunized twice with vaccines comprising either inactivated influenza virus (iFlu3 containing strains A/Swine, MRC-11 and X-79), inactivated pseudorabies virus (iPRV), live pseudorabies virus (PRV) or inactivated porcine parvovirus (iPPV) as antigen and SLP/S/W or O/W as adjuvant. Antibody titres in serum 2 or 3 weeks after the second immuniz
Measuring non-extensitivity parameters in a turbulent Couette-Taylor flow
We investigate probability density functions of velocity differences at
different distances r measured in a Couette-Taylor flow for a range of Reynolds
numbers Re. There is good agreement with the predictions of a theoretical model
based on non-extensive statistical mechanics (where the entropies are
non-additive for independent subsystems). We extract the scale-dependent
non-extensitivity parameter q(r, Re) from the laboratory data.Comment: 8 pages, 5 figure
Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study
BACKGROUND: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia
Searches at HERA for Squarks in R-Parity Violating Supersymmetry
A search for squarks in R-parity violating supersymmetry is performed in e^+p
collisions at HERA at a centre of mass energy of 300 GeV, using H1 data
corresponding to an integrated luminosity of 37 pb^(-1). The direct production
of single squarks of any generation in positron-quark fusion via a Yukawa
coupling lambda' is considered, taking into account R-parity violating and
conserving decays of the squarks. No significant deviation from the Standard
Model expectation is found. The results are interpreted in terms of constraints
within the Minimal Supersymmetric Standard Model (MSSM), the constrained MSSM
and the minimal Supergravity model, and their sensitivity to the model
parameters is studied in detail. For a Yukawa coupling of electromagnetic
strength, squark masses below 260 GeV are excluded at 95% confidence level in a
large part of the parameter space. For a 100 times smaller coupling strength
masses up to 182 GeV are excluded.Comment: 32 pages, 14 figures, 3 table
Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer
Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant
Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s
A precise measurement of the inclusive deep-inelastic e^+p scattering cross
section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and
3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in
1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The
double differential cross section, from which the proton structure function
F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is
measured with typically 1% statistical and 3% systematic uncertainties. The
measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise
continuously towards small x for fixed Q^2. The cross section data are combined
with published H1 measurements at high Q^2 for a next-to-leading order DGLAP
QCD analysis.The H1 data determine the gluon momentum distribution in the range
3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20
GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS
collaboration allows the strong coupling constant alpha_s and the gluon
distribution to be simultaneously determined. A value of alpha
_s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with
an additional theoretical uncertainty of about +-0.005, mainly due to the
uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table
Measurements of Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Measurements of transverse energy flow are presented for neutral current
deep-inelastic scattering events produced in positron-proton collisions at
HERA. The kinematic range covers squared momentum transfers Q^2 from 3.2 to
2,200 GeV^2, the Bjorken scaling variable x from 8.10^{-5} to 0.11 and the
hadronic mass W from 66 to 233 GeV. The transverse energy flow is measured in
the hadronic centre of mass frame and is studied as a function of Q^2, x, W and
pseudorapidity. A comparison is made with QCD based models. The behaviour of
the mean transverse energy in the central pseudorapidity region and an interval
corresponding to the photon fragmentation region are analysed as a function of
Q^2 and W.Comment: 26 pages, 8 figures, submitted to Eur. Phys.
Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)
Introduction: Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the
majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first
intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown,
that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein
up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical
endpoints, activities of daily living and quality of life are unknown.
Methods: The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of
Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4)
to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1
(placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their
individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be
receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious
adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs
and the performance of physical examinations including cardiological signs. The primary outcome is the change in the
Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich
ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life,
functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the upregulation of the frataxin protein level, safety and survival/death.
Perspective: The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic
therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide
treatment in patients with Friedreich ataxia
Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Deep-inelastic positron-proton interactions at low values of Bjorken-x down
to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons
are studied with the H1 experiment at HERA. The inclusive cross section for
pi^0 mesons produced at small angles with respect to the proton remnant (the
forward region) is presented as a function of the transverse momentum and
energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x.
Measurements are also presented of the transverse energy flow in events
containing a forward pi^0 meson. Hadronic final state calculations based on QCD
models implementing different parton evolution schemes are confronted with the
data.Comment: 27 pages, 8 figures and 3 table
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
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