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Preclinical translation of exosomes derived from mesenchymal stem/stromal cells.
Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation
Shifting the Universe: Early Dark Energy and Standard Rulers
The presence of dark energy at high redshift influences both the cosmic sound
horizon and the distance to last scattering of the cosmic microwave background.
We demonstrate that through the degeneracy in their ratio, early dark energy
can lie hidden in the CMB temperature and polarization spectra, leading to an
unrecognized shift in the sound horizon. If the sound horizon is then used as a
standard ruler, as in baryon acoustic oscillations, then the derived
cosmological parameters can be nontrivially biased. Fitting for the absolute
ruler scale (just as supernovae must be fit for the absolute candle magnitude)
removes the bias but decreases the leverage of the BAO technique by a factor 2.Comment: 6 pages, 3 figure
Polarization Diffusion from Spacetime Uncertainty
A model of Lorentz invariant random fluctuations in photon polarization is
presented. The effects are frequency dependent and affect the polarization of
photons as they propagate through space. We test for this effect by confronting
the model with the latest measurements of polarization of Cosmic Microwave
Background (CMB) photons.Comment: 4 pages, 1 figur
Statistical Isotropy violation of the CMB brightness fluctuations
Certain anomalies at large angular scales in the cosmic microwave background
measured by WMAP have been suggested as possible evidence of breakdown of
statistical isotropy(SI). Most CMB photons free-stream to the present from the
surface of last scattering. It is thus reasonable to expect statistical
isotropy violation in the CMB photon distribution observed now to have
originated from SI violation in the baryon-photon fluid at last scattering, in
addition to anisotropy of the primordial power spectrum studied earlier in
literature.
We consider the generalized anisotropic brightness distribution fluctuations,
(at conformal time ) in contrast to the
SI case where it is simply a function of and . The brightness fluctuations expanded in Bipolar Spherical Harmonic
(BipoSH) series, can then be written as where terms encode deviations from statistical isotropy. We
study the evolution of from
non-zero terms at last
scattering. Similar to the SI case, power at small spherical harmonic (SH)
multipoles of at the last
scattering, is transferred to at
larger SH multipoles. The structural similarity is more apparent in the
asymptotic expression for large values of the final SH multipoles. This
formalism allows an elegant identification of any SI violation observed today
to a possible origin in the SI violation present in the baryon-photon fluid
(eg., due to the presence of significant magnetic field).Comment: 14 pages, 4 figures, added illustrative example of SI violation in
baryon-photon fluid, matches version accepted for publication in Phys. Rev.
A Measurement of the Angular Power Spectrum of the CMB from l = 100 to 400
We report on a measurement of the angular spectrum of the CMB between
and made at 144 GHz from Cerro Toco in the
Chilean altiplano. When the new data are combined with previous data at 30 and
40 GHz, taken with the same instrument observing the same section of sky, we
find: 1) a rise in the angular spectrum to a maximum with K at and a fall at , thereby localizing the peak
near ; and 2) that the anisotropy at has the
spectrum of the CMB.Comment: 4 pages, 2 figures. Revised version; includes Ned Wright's postscript
fix. Accepted by ApJL. Website at http://physics.princeton.edu/~cmb
Modulation of CMB polarization with a warm rapidly-rotating half-wave plate on the Atacama B-Mode Search (ABS) instrument
We evaluate the modulation of Cosmic Microwave Background (CMB) polarization
using a rapidly-rotating, half-wave plate (HWP) on the Atacama B-Mode Search
(ABS). After demodulating the time-ordered-data (TOD), we find a significant
reduction of atmospheric fluctuations. The demodulated TOD is stable on time
scales of 500-1000 seconds, corresponding to frequencies of 1-2 mHz. This
facilitates recovery of cosmological information at large angular scales, which
are typically available only from balloon-borne or satellite experiments. This
technique also achieves a sensitive measurement of celestial polarization
without differencing the TOD of paired detectors sensitive to two orthogonal
linear polarizations. This is the first demonstration of the ability to remove
atmospheric contamination at these levels from a ground-based platform using a
rapidly-rotating HWP.Comment: 8 pages, 8 figures, Published in RSI under the title "Modulation of
cosmic microwave background polarization with a warm rapidly rotating
half-wave plate on the Atacama B-Mode Search instrument.
Five-Year Wilkinson Microwave Anisotropy Probe (WMAP) Observations: Bayesian Estimation of CMB Polarization Maps
We describe a sampling method to estimate the polarized CMB signal from
observed maps of the sky. We use a Metropolis-within-Gibbs algorithm to
estimate the polarized CMB map, containing Q and U Stokes parameters at each
pixel, and its covariance matrix. These can be used as inputs for cosmological
analyses. The polarized sky signal is parameterized as the sum of three
components: CMB, synchrotron emission, and thermal dust emission. The polarized
Galactic components are modeled with spatially varying power law spectral
indices for the synchrotron, and a fixed power law for the dust, and their
component maps are estimated as by-products. We apply the method to simulated
low resolution maps with pixels of side 7.2 degrees, using diagonal and full
noise realizations drawn from the WMAP noise matrices. The CMB maps are
recovered with goodness of fit consistent with errors. Computing the likelihood
of the E-mode power in the maps as a function of optical depth to reionization,
tau, for fixed temperature anisotropy power, we recover tau=0.091+-0.019 for a
simulation with input tau=0.1, and mean tau=0.098 averaged over 10 simulations.
A `null' simulation with no polarized CMB signal has maximum likelihood
consistent with tau=0. The method is applied to the five-year WMAP data, using
the K, Ka, Q and V channels. We find tau=0.090+-0.019, compared to
tau=0.086+-0.016 from the template-cleaned maps used in the primary WMAP
analysis. The synchrotron spectral index, beta, averaged over high
signal-to-noise pixels with standard deviation sigma(beta)<0.25, but excluding
~6% of the sky masked in the Galactic plane, is -3.03+-0.04. This estimate does
not vary significantly with Galactic latitude, although includes an informative
prior.Comment: 11 pages, 9 figures, matches version accepted by Ap
Cross-Correlation Detection of Point Sources in WMAP First Year Data
We apply a Cross-correlation (CC) method developed previously for detecting
gamma-ray point sources to the WMAP first year data by using the Point-Spread
Function of WMAP and obtain a full sky CC coefficient map. Analyzing this map,
we find that the CC method is a powerful tool to examine the WMAP foreground
residuals which can be further cleaned accordingly. Evident foreground signals
are found in WMAP foreground cleaned maps and Tegmark cleaned map. In this
process 101 point-sources are detected, and 26 of them are new sources besides
the originally listed WMAP 208 sources. We estimate the flux of these new
sources and verify them by another method. As a result, a revised mask file
based on the WMAP first year data is produced by including these new sources.Comment: 14 pages, 10 figures; accepted for publication by ChJA
Five-Year Wilkinson Microwave Anisotropy Probe (WMAP) Observations: Data Processing, Sky Maps, and Basic Results
We present new full-sky temperature and polarization maps in five frequency
bands from 23 to 94 GHz, based on data from the first five years of the WMAP
sky survey. The five-year maps incorporate several improvements in data
processing made possible by the additional years of data and by a more complete
analysis of the instrument calibration and in-flight beam response. We present
several new tests for systematic errors in the polarization data and conclude
that Ka band data (33 GHz) is suitable for use in cosmological analysis, after
foreground cleaning. This significantly reduces the overall polarization
uncertainty. With the 5 year WMAP data, we detect no convincing deviations from
the minimal 6-parameter LCDM model: a flat universe dominated by a cosmological
constant, with adiabatic and nearly scale-invariant Gaussian fluctuations.
Using WMAP data combined with measurements of Type Ia supernovae and Baryon
Acoustic Oscillations, we find (68% CL uncertainties): Omega_bh^2 = 0.02267 \pm
0.00059, Omega_ch^2 = 0.1131 \pm 0.0034, Omega_Lambda = 0.726 \pm 0.015, n_s =
0.960 \pm 0.013, tau = 0.084 \pm 0.016, and Delta_R^2 = (2.445 \pm 0.096) x
10^-9. From these we derive: sigma_8 = 0.812 \pm 0.026, H_0 = 70.5 \pm 1.3
km/s/Mpc, z_{reion} = 10.9 \pm 1.4, and t_0 = 13.72 \pm 0.12 Gyr. The new limit
on the tensor-to-scalar ratio is r < 0.22 (95% CL). We obtain tight,
simultaneous limits on the (constant) dark energy equation of state and spatial
curvature: -0.14 < 1+w < 0.12 and -0.0179 < Omega_k < 0.0081 (both 95% CL). The
number of relativistic degrees of freedom (e.g. neutrinos) is found to be
N_{eff} = 4.4 \pm 1.5, consistent with the standard value of 3.04. Models with
N_{eff} = 0 are disfavored at >99.5% confidence.Comment: 46 pages, 13 figures, and 7 tables. Version accepted for publication,
ApJS, Feb-2009. Includes 5-year dipole results and additional references.
Also available at
http://lambda.gsfc.nasa.gov/product/map/dr3/map_bibliography.cf
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