1,693 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
Characterization of nanomedicines’ surface coverage using molecular probes and capillary electrophoresis
International audienceA faithful characterization of nanomedicine (NM) is needed for a better understanding of their in vivo outcomes. Size and surface charge are studied with well-established methods. However, other relevant parameters for the understanding of NM behavior in vivo remain largely inaccessible. For instance, the reactive surface of nanomedicines, which are often grafted with macromolecules to decrease their recognition by the immune system, is excluded from a systematic characterization. Yet, it is known that a subtle modification of NMs' surface characteristics (grafting density, molecular architecture and conformation of macromolecules) is at the root of major changes in the presence of biological components. In this work, a method that investigates the steric hindrance properties of the NMs’ surface coverage based on its capacity to exclude or allow adsorption of well-defined proteins was developed based on capillary electrophoresis. A series of proteins with different molecular weights (MW) were used as molecular probes to screen their adsorption behavior on nanoparticles bearing different molecular architectures at their surface. This novel strategy evaluating to some degree a functionality of NMs can bring additional information about their shell property and might allow for a better perception of their behavior in the presence of biological components. The developed method could discriminate nanoparticles with a high surface coverage excluding high MW proteins from nanoparticles with a low surface coverage that allowed high MW proteins to adsorb on their surface. The method has the potential for further standardization and automation for a routine use. It can be applied in quality control of NMs and to investigate interactions between proteins and NM in different situations
Type Ia Supernova Spectral Line Ratios as Luminosity Indicators
Type Ia supernovae have played a crucial role in the discovery of the dark
energy, via the measurement of their light curves and the determination of the
peak brightness via fitting templates to the observed lightcurve shape. Two
spectroscopic indicators are also known to be well correlated with peak
luminosity. Since the spectroscopic luminosity indicators are obtained directly
from observed spectra, they will have different systematic errors than do
measurements using photometry. Additionally, these spectroscopic indicators may
be useful for studies of effects of evolution or age of the SNe Ia progenitor
population. We present several new variants of such spectroscopic indicators
which are easy to automate and which minimize the effects of noise. We show
that these spectroscopic indicators can be measured by proposed JDEM missions
such as SNAP and JEDI.Comment: 50 pages, 19 figures, 24 tables, submitted to Ap
Constraining Type Ia supernova models: SN 2011fe as a test case
The nearby supernova SN 2011fe can be observed in unprecedented detail.
Therefore, it is an important test case for Type Ia supernova (SN Ia) models,
which may bring us closer to understanding the physical nature of these
objects. Here, we explore how available and expected future observations of SN
2011fe can be used to constrain SN Ia explosion scenarios. We base our
discussion on three-dimensional simulations of a delayed detonation in a
Chandrasekhar-mass white dwarf and of a violent merger of two white
dwarfs-realizations of explosion models appropriate for two of the most
widely-discussed progenitor channels that may give rise to SNe Ia. Although
both models have their shortcomings in reproducing details of the early and
near-maximum spectra of SN 2011fe obtained by the Nearby Supernova Factory
(SNfactory), the overall match with the observations is reasonable. The level
of agreement is slightly better for the merger, in particular around maximum,
but a clear preference for one model over the other is still not justified.
Observations at late epochs, however, hold promise for discriminating the
explosion scenarios in a straightforward way, as a nucleosynthesis effect leads
to differences in the 55Co production. SN 2011fe is close enough to be followed
sufficiently long to study this effect.Comment: Accepted for publication in The Astrophysical Journal Letter
Standardizing Type Ia Supernova Absolute Magnitudes Using Gaussian Process Data Regression
We present a novel class of models for Type Ia supernova time-evolving
spectral energy distributions (SED) and absolute magnitudes: they are each
modeled as stochastic functions described by Gaussian processes. The values of
the SED and absolute magnitudes are defined through well-defined regression
prescriptions, so that data directly inform the models. As a proof of concept,
we implement a model for synthetic photometry built from the spectrophotometric
time series from the Nearby Supernova Factory. Absolute magnitudes at peak
brightness are calibrated to 0.13 mag in the -band and to as low as 0.09 mag
in the blueshifted -band, where the dispersion includes
contributions from measurement uncertainties and peculiar velocities. The
methodology can be applied to spectrophotometric time series of supernovae that
span a range of redshifts to simultaneously standardize supernovae together
with fitting cosmological parameters.Comment: 47 pages, 15 figures, accepted for publication by Astrophysical
Journa
Atmospheric extinction properties above Mauna Kea from the Nearby Supernova Factory spectro-photometric data set
We present a new atmospheric extinction curve for Mauna Kea spanning
3200--9700 \AA. It is the most comprehensive to date, being based on some 4285
standard star spectra obtained on 478 nights spread over a period of 7 years
obtained by the Nearby SuperNova Factory using the SuperNova Integral Field
Spectrograph. This mean curve and its dispersion can be used as an aid in
calibrating spectroscopic or imaging data from Mauna Kea, and in estimating the
calibration uncertainty associated with the use of a mean extinction curve. Our
method for decomposing the extinction curve into physical components, and the
ability to determine the chromatic portion of the extinction even on cloudy
nights, is described and verified over the wide range of conditions sampled by
our large dataset. We demonstrate good agreement with atmospheric science data
obtain at nearby Mauna Loa Observatory, and with previously published
measurements of the extinction above Mauna Kea.Comment: 22 pages, 24 figures, 6 table
Measuring cosmic bulk flows with Type Ia Supernovae from the Nearby Supernova Factory
Context. Our Local Group of galaxies appears to be moving relative to the
cosmic microwave background with the source of the peculiar motion still
uncertain. While in the past this has been studied mostly using galaxies as
distance indicators, the weight of type Ia supernovae (SNe Ia) has increased
recently with the continuously improving statistics of available low-redshift
supernovae.
Aims. We measured the bulk flow in the nearby universe ()
using 117 SNe Ia observed by the Nearby Supernova Factory, as well as the
Union2 compilation of SN Ia data already in the literature.
Methods. The bulk flow velocity was determined from SN data binned in
redshift shells by including a coherent motion (dipole) in a cosmological fit.
Additionally, a method of spatially smoothing the Hubble residuals was used to
verify the results of the dipole fit. To constrain the location and mass of a
potential mass concentration (e.g., the Shapley supercluster) responsible for
the peculiar motion, we fit a Hubble law modified by adding an additional mass
concentration.
Results. The analysis shows a bulk flow that is consistent with the direction
of the CMB dipole up to , thereby doubling the volume over which
conventional distance measures are sensitive to a bulk flow. We see no
significant turnover behind the center of the Shapley supercluster. A simple
attractor model in the proximity of the Shapley supercluster is only marginally
consistent with our data, suggesting the need for another, more distant source.
In the redshift shell , we constrain the bulk flow velocity to
(68% confidence level) for the direction of the CMB
dipole, in contradiction to recent claims of the existence of a large-amplitude
dark flow.Comment: 12 pages, 5 figures, added corrigendum
(http://adsabs.harvard.edu/abs/2015A%26A...578C...1F
Evidence of Environmental Dependencies of Type Ia Supernovae from the Nearby Supernova Factory indicated by Local H{\alpha}
(Abridged) We study the host galaxy regions in close proximity to Type Ia
supernovae (SNe Ia) to analyze relations between the properties of SN Ia events
and environments most similar to where their progenitors formed. We focus on
local H\alpha\ emission as an indicator of young environments. The Nearby
Supernova Factory has obtained flux-calibrated spectral timeseries for SNe Ia
using integral field spectroscopy, allowing the simultaneous measurement of the
SN and its immediate vicinity. For 89 SNe Ia we measure H\alpha\ emission
tracing ongoing star formation within a 1 kpc radius around each SN. This
constitutes the first direct study of the local environment for a large sample
of SNe Ia also having accurate luminosity, color and stretch measurements. We
find that SNe Ia with local H\alpha\ emission are redder by 0.036+/-0.017 mag,
and that the previously-noted correlation between stretch and host mass is
entirely driven by the SNe Ia coming from passive regions. Most importantly,
the mean standardized brightness for SNe Ia with local H\alpha\ emission is
0.094+/-0.031 mag fainter than for those without. This offset arises from a
bimodal structure in the Hubble residuals, that also explains the
previously-known host-mass bias. We combine this bimodality with the cosmic
star-formation rate to predict changes with redshift in the mean SN Ia
brightness and the host-mass bias. This change is confirmed using high-redshift
SNe Ia from the literature. These environmental dependences point to remaining
systematic errors in SNe Ia standardization. The observed brightness offset is
predicted to cause a significant bias in measurements of the dark energy
equation of state. Recognition of these effects offers new opportunities to
improve SNe Ia as cosmological probes - e.g. SNe Ia having local H\alpha\
emission are more homogeneous, having a brightness dispersion of 0.105+/-0.012
mag.Comment: accepted for publication in Section 3. Cosmology of A&A (The official
date of acceptance is 30/08/2013
Host Galaxy Properties and Hubble Residuals of Type Ia Supernovae from the Nearby Supernova Factory
We examine the relationship between Type Ia Supernova (SN Ia) Hubble
residuals and the properties of their host galaxies using a sample of 115 SNe
Ia from the Nearby Supernova Factory (SNfactory). We use host galaxy stellar
masses and specific star-formation rates fitted from photometry for all hosts,
as well as gas-phase metallicities for a subset of 69 star-forming (non-AGN)
hosts, to show that the SN Ia Hubble residuals correlate with each of these
host properties. With these data we find new evidence for a correlation between
SN Ia intrinsic color and host metallicity. When we combine our data with those
of other published SN Ia surveys, we find the difference between mean SN Ia
brightnesses in low and high mass hosts is 0.077 +- 0.014 mag. When viewed in
narrow (0.2 dex) bins of host stellar mass, the data reveal apparent plateaus
of Hubble residuals at high and low host masses with a rapid transition over a
short mass range (9.8 <= log(M_*/M_Sun) <= 10.4). Although metallicity has been
a favored interpretation for the origin of the Hubble residual trend with host
mass, we illustrate how dust in star-forming galaxies and mean SN Ia progenitor
age both evolve along the galaxy mass sequence, thereby presenting equally
viable explanations for some or all of the observed SN Ia host bias.Comment: 20 pages, 11 figures, accepted for publication in Ap
Type Ia Supernova Hubble Residuals and Host-Galaxy Properties
Kim et al. (2013) [K13] introduced a new methodology for determining
peak-brightness absolute magnitudes of type Ia supernovae from multi-band light
curves. We examine the relation between their parameterization of light curves
and Hubble residuals, based on photometry synthesized from the Nearby Supernova
Factory spectrophotometric time series, with global host-galaxy properties. The
K13 Hubble residual step with host mass is mag for a supernova
subsample with data coverage corresponding to the K13 training; at , the step is not significant and lower than previous measurements.
Relaxing the data coverage requirement the Hubble residual step with host mass
is mag for the larger sample; a calculation using the modes of
the distributions, less sensitive to outliers, yields a step of 0.019 mag. The
analysis of this article uses K13 inferred luminosities, as distinguished from
previous works that use magnitude corrections as a function of SALT2 color and
stretch parameters: Steps at significance are found in SALT2 Hubble
residuals in samples split by the values of their K13 and
light-curve parameters. affects the light-curve width and color around
peak (similar to the and stretch parameters), and
affects colors, the near-UV light-curve width, and the light-curve decline 20
to 30 days after peak brightness. The novel light-curve analysis, increased
parameter set, and magnitude corrections of K13 may be capturing features of
SN~Ia diversity arising from progenitor stellar evolution.Comment: 17 pages, 6 figures. Accepted by Astrophysical Journa
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