1,141 research outputs found
Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells
Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade
The Extinction Properties of and Distance to the Highly Reddened Type Ia Supernova SN 2012cu
Correction of Type Ia Supernova brightnesses for extinction by dust has
proven to be a vexing problem. Here we study the dust foreground to the highly
reddened SN 2012cu, which is projected onto a dust lane in the galaxy NGC 4772.
The analysis is based on multi-epoch, spectrophotometric observations spanning
3,300 - 9,200 {\AA}, obtained by the Nearby Supernova Factory. Phase-matched
comparison of the spectroscopically twinned SN 2012cu and SN 2011fe across 10
epochs results in the best-fit color excess of (E(B-V), RMS) = (1.00, 0.03) and
total-to-selective extinction ratio of (RV , RMS) = (2.95, 0.08) toward SN
2012cu within its host galaxy. We further identify several diffuse interstellar
bands, and compare the 5780 {\AA} band with the dust-to-band ratio for the
Milky Way. Overall, we find the foreground dust-extinction properties for SN
2012cu to be consistent with those of the Milky Way. Furthermore we find no
evidence for significant time variation in any of these extinction tracers. We
also compare the dust extinction curve models of Cardelli et al. (1989),
O'Donnell (1994), and Fitzpatrick (1999), and find the predictions of
Fitzpatrick (1999) fit SN 2012cu the best. Finally, the distance to NGC4772,
the host of SN 2012cu, at a redshift of z = 0.0035, often assigned to the Virgo
Southern Extension, is determined to be 16.61.1 Mpc. We compare this
result with distance measurements in the literature.Comment: 48 pages, 13 figures. Accepted for publication in The Astrophysical
Journal. The spectral time series data presented in this article can be found
at http://snfactory.lbl.gov/snf/data
DUNE: The Dark Universe Explorer
Understanding the nature of Dark Matter and Dark Energy is one of the most pressing issues in cosmology and fundamental physics. The purpose of the DUNE (Dark UNiverse Explorer) mission is to study these two cosmological components with high precision, using a space-based weak lensing survey as its primary science driver. Weak lensing provides a measure of the distribution of dark matter in the universe and of the impact of dark energy on the growth of structures. DUNE will also include a complementary supernovae survey to measure the expansion history of the universe, thus giving independent additional constraints on dark energy. The baseline concept consists of a 1.2m telescope with a 0.5 square degree optical CCD camera. It is designed to be fast with reduced risks and costs, and to take advantage of the synergy between ground-based and space observations. Stringent requirements for weak lensing systematics were shown to be achievable with the baseline concept. This will allow DUNE to place strong constraints on cosmological parameters, including the equation of state parameter of the dark energy and its evolution from redshift 0 to 1. DUNE is the subject of an ongoing study led by the French Space Agency (CNES), and is being proposed for ESA's Cosmic Vision programme
CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancers xenografts
CD44 is a marker of tumour-initiating cells and is upregulated in invasive breast carcinoma; however, its role in the cancer progression is unknown. Here, we show that antibody-mediated CD44-targeting in human breast cancer xenografts (HBCx) significantly reduces tumour growth and that this effect is associated to induction of growth-inhibiting factors. Moreover, treatment with this antibody prevents tumour relapse after chemotherapy-induced remission in a basal-like HBCx
Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance
This paper presents DELPHI measurements and interpretations of
cross-sections, forward-backward asymmetries, and angular distributions, for
the e+e- -> ffbar process for centre-of-mass energies above the Z resonance,
from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are
consistent with the predictions of the Standard Model and are used to study a
variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering
and several models which include physics beyond the Standard Model: the
exchange of Z' bosons, contact interactions between fermions, the exchange of
gravitons in large extra dimensions and the exchange of sneutrino in R-parity
violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.
Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector
Inclusive J/psi production in photon-photon collisions has been observed at
LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X
is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an
integrated luminosity of 617 pb^{-1}, yielding a cross-section of
sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the
event shapes of different types of gamma gamma processes in the PYTHIA program,
we conclude that (74 +/- 22)% of the observed J/psi events are due to
`resolved' photons, the dominant contribution of which is most probably due to
the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.
A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events
Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the
Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy
and momentum constraint methods. The results are expressed as deviations from
the nominal LEP centre-of-mass energy, measured using other techniques. The
results are found to be compatible with the LEP Energy Working Group estimates
for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.
A Measurement of the Tau Hadronic Branching Ratios
The exclusive and semi-exclusive branching ratios of the tau lepton hadronic
decay modes (h- v_t, h- pi0 v_t, h- pi0 pi0 v_t, h- \geq 2pi0 v_t, h- \geq 3pi0
v_t, 2h- h+ v_t, 2h- h+ pi0 v_t, 2h- h+ \geq 2pi0 v_t, 3h- 2h+ v_t and 3h- 2h+
\geq 1pi0 v_t) were measured with data from the DELPHI detector at LEP.Comment: 53 pages, 18 figures, Accepted by Eur. Phys. J.
Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0
Soft photons inside hadronic jets converted in front of the DELPHI main
tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the
kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to
the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the
experimental data as compared to the Monte Carlo predictions is observed. This
excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/-
0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected
level of the inner hadronic bremsstrahlung (which is not included in the Monte
Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the
excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8),
which is similar in strength to the anomalous soft photon signal observed in
fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.
Determination of the b quark mass at the M_Z scale with the DELPHI detector at LEP
An experimental study of the normalized three-jet rate of b quark events with
respect to light quarks events (light= \ell \equiv u,d,s) has been performed
using the CAMBRIDGE and DURHAM jet algorithms. The data used were collected by
the DELPHI experiment at LEP on the Z peak from 1994 to 2000. The results are
found to agree with theoretical predictions treating mass corrections at
next-to-leading order. Measurements of the b quark mass have also been
performed for both the b pole mass: M_b and the b running mass: m_b(M_Z). Data
are found to be better described when using the running mass. The measurement
yields: m_b(M_Z) = 2.85 +/- 0.18 (stat) +/- 0.13 (exp) +/- 0.19 (had) +/- 0.12
(theo) GeV/c^2 for the CAMBRIDGE algorithm. This result is the most precise
measurement of the b mass derived from a high energy process. When compared to
other b mass determinations by experiments at lower energy scales, this value
agrees with the prediction of Quantum Chromodynamics for the energy evolution
of the running mass. The mass measurement is equivalent to a test of the
flavour independence of the strong coupling constant with an accuracy of 7
permil.Comment: 24 pages, 10 figures, Accepted by Eur. Phys. J.
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