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

Initial Hubble Diagram Results from the Nearby Supernova Factory

The use of Type Ia supernovae as distance indicators led to the discovery of the accelerating expansion of the universe a decade ago. Now that large second generation surveys have significantly increased the size and quality of the high-redshift sample, the cosmological constraints are limited by the currently available sample of ~50 cosmologically useful nearby supernovae. The Nearby Supernova Factory addresses this problem by discovering nearby supernovae and observing their spectrophotometric time development. Our data sample includes over 2400 spectra from spectral timeseries of 185 supernovae. This talk presents results from a portion of this sample including a Hubble diagram (relative distance vs. redshift) and a description of some analyses using this rich dataset.Comment: Short version of proceedings for ICHEP08, Philadelphia PA, July 2008; see v1 for full-length versio

In-capillary immuno-preconcentration with circulating bio-functionalized magnetic beads for capillary electrophoresis

This study reports on the conception of magneto-Capillary Electrophoresis (magneto-CE), an approach integrating immuno-capture on circulating bio-functionalized magnetic beads into a unique capillary for preconcentration and electrokinetic separation. This hybrid mode is an evolution of in-capillary magnetic bead-based operation from static cluster format to dynamic configuration where beads are allowed to controllably circulate inside a CE capillary for interaction improvement. To implement the magneto-CE operation, a purpose-made instrument was constructed, allowing visual observation of the movement of the magnetic beads. We applied a new methodological strategy for determination of the amyloid beta peptide (A beta 1-42), which is as an established biomarker for molecular diagnosis of Alzheimer's disease (AD). The methodology is based on magneto-immuno-capture of fluorescently labeled A beta 1-42 followed by a chemical elution with a basic solution prior to CE separation with laser induced fluorescent (LIF) detection. The superiority of this dynamic configuration of magneto-CE was demonstrated for this target analyte, with sample pretreatment and separation being performed in-capillary without any delay in between and without any waste of pretreated sample, which otherwise would not be the case with offline/batch-wise operation. (C) 2019 Elsevier B.V. All rights reserved

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 $B$ brightness are calibrated to 0.13 mag in the $g$-band and to as low as 0.09 mag in the $z=0.25$ blueshifted $i$-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 ($0.015 < z < 0.1$) 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 $z \sim 0.06$, 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 $0.06 < z < 0.1$, we constrain the bulk flow velocity to $< 240~\textrm{km s}^{-1}$ (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

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

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