Glucocorticoids delivered by inorganic‐organic hybrid nanoparticles mitigate acute graft‐versus‐host disease and sustain graft‐versus‐leukemia activity

Glucocorticoids (GCs) are widely used to treat acute graft‐versus‐host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft‐versus‐leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering GCs with the help of inorganic–organic hybrid nanoparticles (IOH‐NPs) that preferentially target myeloid cells. IOH‐NPs containing the GC betamethasone (BMP‐NPs) efficiently reduced morbidity, mortality, and tissue damage in a totally MHC mismatched mouse model of aGvHD. Therapeutic activity was lost in mice lacking the GC receptor (GR) in myeloid cells, confirming the cell type specificity of our approach. BMP‐NPs had no relevant systemic activity but suppressed cytokine and chemokine gene expression locally in the small intestine, which presumably explains their mode of action. Most importantly, BMP‐NPs delayed the development of an adoptively transferred B cell lymphoma better than the free drug, although the overall incidence was unaffected. Our findings thus suggest that employing IOH‐NPs could diminish the risk of relapse associated with GC therapy of aGvHD patients while still allowing to efficiently ameliorate the disease

Variabilidade temporal e espacial da umidade do solo na camada superficial de uma encosta do Loess Plateau na China

Surface soil moisture exhibits an important variability in terms of spatial and temporal domains, which may result in critical uncertainties for agricultural water management. The purposes of this study were (i) to characterize the temporal dynamics and stability of the spatial variability of the surface 0-6 cm soil water content θon a hill-slope; (ii) to investigate issues related to soil moisture conditions including dominating factors on soil moisture and to the estimation of the mean θ. During a period of more than one month θwas measured on thirteen days by Frequency Domain Reflectometry using a 10 x 10 m grid of measurement points covering a 60 x 280 m domain within a hill-slope of the Loess Plateau in China. Soil water content exhibited a moderate variability for each measurement date, and the correlation length (l) for θranged from 8.4 to 27.7 m. With the soil becoming drier, l decreased, the CV% and the sampling number for accurate mean θestimation increased. Aspect, elevation, organic matter content, clay content, and bulk density were the main influencing factors, whose extent of influence weakened with decreasing θ. Based on time stability analysis and on the correlation of mean relative difference of θwith the relative difference of dominating factors, mean q values were well estimated, with a better accuracy under wetter conditions.A umidade da camada superficial do solo apresenta uma variabilidade importante nos domínios espacial e temporal, que pode levar a incertezas críticas para o manejo agrícola da água. Os objetivos deste estudo incluíram: (i) a caracterização da dinâmica temporal e da estabilidade da variabilidade espacial da umidade θda camada 0-6 cm em uma encosta em declive; (ii) investigação de parâmetros ligados às condições de umidade, incluindo fatores dominantes da umidade na estimativa de um valor médio de q. Durante um período de mais de um mês, q foi medida em 13 dias com auxílio da técnica da Refletometria do Domínio da Frequência, em uma grade de 10 x 10 cm, cobrindo uma área de 60 x 280 m, situada em uma encosta do Loess Plateau da China. A umidade do solo apresentou variabilidade moderada em cada data de medida e o alcance da correlação (l) para q variou de 8,4 a 27,7 m. Com o solo mais seco, l decresceu, o CV% e o número de amostras necessário para obter uma média precisa, aumentaram. O aspecto, a elevação, o conteúdo de matéria orgânica e a densidade do solo foram os principais fatores interferentes na umidade, cuja intensidade de influência diminuiu com a umidade. Baseado na análise de estabilidade temporal e na correlação da diferença relativa média de θcom a diferença relativa média dos fatores dominantes, valores médios de q puderam ser mais bem estimados, com maior precisão sobre condições mais úmidas.CAS of China - Chinese Academy of SciencesNational Natural Sciences Foundation of Chin

Soil water content temporal-spatial variability of the surface layer of a Loess Plateau hillside in China

Surface soil moisture exhibits an important variability in terms of spatial and temporal domains, which may result in critical uncertainties for agricultural water management. The purposes of this study were (i) to characterize the temporal dynamics and stability of the spatial variability of the surface 0-6 cm soil water content θon a hill-slope; (ii) to investigate issues related to soil moisture conditions including dominating factors on soil moisture and to the estimation of the mean θ. During a period of more than one month θwas measured on thirteen days by Frequency Domain Reflectometry using a 10 x 10 m grid of measurement points covering a 60 x 280 m domain within a hill-slope of the Loess Plateau in China. Soil water content exhibited a moderate variability for each measurement date, and the correlation length (l) for θranged from 8.4 to 27.7 m. With the soil becoming drier, l decreased, the CV% and the sampling number for accurate mean θestimation increased. Aspect, elevation, organic matter content, clay content, and bulk density were the main influencing factors, whose extent of influence weakened with decreasing θ. Based on time stability analysis and on the correlation of mean relative difference of θwith the relative difference of dominating factors, mean q values were well estimated, with a better accuracy under wetter conditions.A umidade da camada superficial do solo apresenta uma variabilidade importante nos domínios espacial e temporal, que pode levar a incertezas críticas para o manejo agrícola da água. Os objetivos deste estudo incluíram: (i) a caracterização da dinâmica temporal e da estabilidade da variabilidade espacial da umidade θda camada 0-6 cm em uma encosta em declive; (ii) investigação de parâmetros ligados às condições de umidade, incluindo fatores dominantes da umidade na estimativa de um valor médio de q. Durante um período de mais de um mês, q foi medida em 13 dias com auxílio da técnica da Refletometria do Domínio da Frequência, em uma grade de 10 x 10 cm, cobrindo uma área de 60 x 280 m, situada em uma encosta do "Loess Plateau" da China. A umidade do solo apresentou variabilidade moderada em cada data de medida e o alcance da correlação (l) para q variou de 8,4 a 27,7 m. Com o solo mais seco, l decresceu, o CV% e o número de amostras necessário para obter uma média precisa, aumentaram. O aspecto, a elevação, o conteúdo de matéria orgânica e a densidade do solo foram os principais fatores interferentes na umidade, cuja intensidade de influência diminuiu com a umidade. Baseado na análise de estabilidade temporal e na correlação da diferença relativa média de θcom a diferença relativa média dos fatores dominantes, valores médios de q puderam ser mais bem estimados, com maior precisão sobre condições mais úmidas

Variabilidade espacial de propriedades hídricas do solo de uma encosta do "Loess Plateau" da China

The understanding of the structure of the spatial variability of soil surface hydraulic properties on steep slopes is important for modeling infiltration and runoff processes. The objective of this study was to investigate the spatial variability of these properties on a steep slope of the Loess Plateau in northwest China. A 9600 m² area was systematically sampled in a grid of 106 points spaced 10 m x 10 m. Hydraulic properties were determined with a disc infiltrometer under multiple pressure heads (-15, -9, -6, -3, 0 cm) at each sample point. Classical and geo-statistical methods were used for data analysis. The results indicated that the variation of Gardner's a and hydraulic conductivities at all applied pressure heads was moderate and the heterogeneity for hydraulic conductivities increased as the applied pressure head increased. Along the slope, hydraulic conductivities generally decreased downwards, while the Gardner's a fluctuated slightly. The Gardner's a of the shaded aspect of the slope was greater than that of the sunny aspect. The hydraulic conductivities of the shaded aspect were greater at higher pressure heads as compared to the sunny aspect, but lower than those of the sunny aspect at lower pressure heads. Correlation analysis showed a negative correlation between hydraulic conductivity and soil organic matter and clay (A compreensão da estrutura da variabilidade especial das propriedades hidráulicas do solo de encostas íngremes é importante na modelagem dos processos de infiltração e de escoamento superficial da água. O objetivo deste estudo foi investigar a variabilidade destas propriedades em uma encosta íngreme do "Loess Plateau" do noroeste da China. Uma área de 9600 m² foi sistematicamente amostrada em um grid de 106 pontos espaçados de 10 m x 10 m. As propriedades hídricas foram determinadas com um infiltrômetro de disco operando sob múltiplas cargas hidráulicas (-15, -9, -6, -3, 0 cm) em cada ponto de observação. Métodos clássicos e geoestatísticos foram empregados na análise dos dados. Os resultados mostraram que a variação do índice a de Gardner e das condutividades hidráulicas em todas as cargas aplicadas foi moderada e que a heterogeneidade das condutividades hidráulicas aumentou à medida que a carga hidráulica aumentava. Na direção do declive, as condutividades geralmente decresceram a jusante, enquanto os a de Gardner flutuavam moderadamente. Os a de Gardner das encostas sombreadas foram maiores do que os das encostas ensolaradas. As condutividades hidráulicas das encostas sombreadas foram maiores para cargas hidráulicas maiores em comparação com as encostas ensolaradas, mas menores que as das encostas ensolaradas para cargas hidráulicas menores. A análise de correlação mostrou uma correlação negativa entre a condutividade hidráulica e os teores de matéria orgânica e argila

Lensed CMB temperature and polarization maps from the Millennium Simulation

We have constructed the first all-sky CMB temperature and polarization lensed maps based on a high-resolution cosmological N-body simulation, the Millennium Simulation (MS). We have exploited the lensing potential map obtained using a map-making procedure (Carbone et al. 2008) which integrates along the line-of-sight the MS dark matter distribution by stacking and randomizing the simulation boxes up to $z = 127$, and which semi-analytically supplies the large-scale power in the angular lensing potential that is not correctly sampled by the N-body simulation. The lensed sky has been obtained by properly modifying the latest version of the LensPix code (Lewis 2005) to account for the MS structures. We have also produced all-sky lensed maps of the so-called $\psi_E$ and $\psi_B$ potentials, which are directly related to the electric and magnetic types of polarization. The angular power spectra of the simulated lensed temperature and polarization maps agree well with semi-analytic estimates up to $l < 2500$, while on smaller scales we find a slight excess of power which we interpret as being due to non-linear clustering in the MS. We also observe how non-linear lensing power in the polarised CMB is transferred to large angular scales by suitably misaligned modes in the CMB and the lensing potential. This work is relevant in view of the future CMB probes, as a way to analyse the lensed sky and disentangle the contribution from primordial gravitational waves.Comment: 13 pages, 11 figures, comments added, MNRAS in pres

Partial CMB maps: bias removal and optimal binning of the angular power spectrum

We present a semi-analytical method to investigate the systematic effects and statistical uncertainties of the calculated angular power spectrum when incomplete spherical maps are used. The computed power spectrum suffers in particular a loss of angular frequency resolution, which can be written as \delta_l ~ \pi/\gamma_max, where \gamma_max is the effective maximum extent of the partial spherical maps. We propose a correction algorithm to reduce systematic effects on the estimated C_l, as obtained from the partial map projection on the spherical harmonic Ylm(l,m) basis. We have derived near optimal bands and weighting functions in l-space for power spectrum calculation using small maps, and a correction algorithm for partially masked spherical maps that contain information on the angular correlations on all scales.Comment: 11 page

Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation

Morphogenesis of a vascular network requires dynamic vessel growth and regression. To investigate the cellular mechanism underlying this process, we deleted focal adhesion kinase (FAK), a key signaling mediator, in endothelial cells (ECs) using Tie2-Cre mice. Targeted FAK depletion occurred efficiently early in development, where mutants exhibited a distinctive and irregular vasculature, resulting in hemorrhage and lethality between embryonic day (e) 10.5 and 11.5. Capillaries and intercapillary spaces in yolk sacs were dilated before any other detectable abnormalities at e9.5, and explants demonstrate that the defects resulted from the loss of FAK and not from organ failure. Time-lapse microscopy monitoring EC behavior during vascular formation in explants revealed no apparent decrease in proliferation or migration but revealed increases in cell retraction and death leading to reduced vessel growth and increased vessel regression. Consistent with this phenotype, ECs derived from mutant embryos exhibited aberrant lamellipodial extensions, altered actin cytoskeleton, and nonpolarized cell movement. This study reveals that FAK is crucial for vascular morphogenesis and the regulation of EC survival and morphology

Mass-varying neutrino in light of cosmic microwave background and weak lensing

We aim to constrain mass-varying neutrino models using large scale structure observations and produce forecast for the Euclid survey. We investigate two models with different scalar field potential and both positive and negative coupling parameters \beta. These parameters correspond to growing or decreasing neutrino mass, respectively. We explore couplings up to |\beta|<5. In the case of the exponential potential, we find an upper limit on $\Omega_\nu h^2$<0.004 at 2-$\sigma$ level. In the case of the inverse power law potential the null coupling can be excluded with more than 2-\sigma significance; the limits on the coupling are \beta>3 for the growing neutrino mass and \beta<-1.5 for the decreasing mass case. This is a clear sign for a preference of higher couplings. When including a prior on the present neutrino mass the upper limit on the coupling becomes |\beta|<3 at 2-$\sigma$ level for the exponential potential. Finally, we present a Fisher forecast using the tomographic weak lensing from an Euclid-like experiment and we also consider the combination with the cosmic microwave background (CMB) temperature and polarisation spectra from a Planck-like mission. If considered alone, lensing data is more efficient in constraining $\Omega_\nu$ with respect to CMB data alone. There is, however, a strong degeneracy in the \beta-$\Omega_\nu h^2$ plane. When the two data sets are combined, the latter degeneracy remains, but the errors are reduced by a factor ~2 for both parameters.Comment: 5 pages, 6 figures. Now published in A&A 500, 657-665 (2009

Dark Energy Perturbations Revisited

In this paper we study the evolution of cosmological perturbations in the presence of dynamical dark energy, and revisit the issue of dark energy perturbations. For a generally parameterized equation of state (EoS) such as w_D(z) = w_0+w_1\frac{z}{1+z}, (for a single fluid or a single scalar field ) the dark energy perturbation diverges when its EoS crosses the cosmological constant boundary w_D=-1. In this paper we present a method of treating the dark energy perturbations during the crossing of the $w_D=-1$ surface by imposing matching conditions which require the induced 3-metric on the hypersurface of w_D=-1 and its extrinsic curvature to be continuous. These matching conditions have been used widely in the literature to study perturbations in various models of early universe physics, such as Inflation, the Pre-Big-Bang and Ekpyrotic scenarios, and bouncing cosmologies. In all of these cases the EoS undergoes a sudden change. Through a detailed analysis of the matching conditions, we show that \delta_D and \theta_D are continuous on the matching hypersurface. This justifies the method used[1-4] in the numerical calculation and data fitting for the determination of cosmological parameters. We discuss the conditions under which our analysis is applicable.Comment: 10 pages and 1 figure

CMB at 2x2 order: the dissipation of primordial acoustic waves and the observable part of the associated energy release

Silk damping of primordial small-scale perturbations in the photon-baryon fluid due to diffusion of photons inevitably creates spectral distortions in the CMB. With the proposed CMB experiment PIXIE it might become possible to measure these distortions and thereby constrain the primordial power spectrum at comoving wavenumbers 50 Mpc^{-1} < k < 10^4 Mpc^{-1}. Since primordial fluctuations in the CMB on these scales are completely erased by Silk damping, these distortions may provide the only way to shed light on otherwise unobservable aspects of inflationary physics. A consistent treatment of the primordial dissipation problem requires going to second order in perturbation theory, while thermalization of these distortions necessitates consideration of second order in Compton scattering energy transfer. Here we give a full 2x2 treatment for the creation and evolution of spectral distortions due to the acoustic dissipation process, consistently including the effect of polarization and photon mixing in the free streaming regime. We show that 1/3 of the total energy (9/4 larger than previous estimates) stored in small-scale temperature perturbations imprints observable spectral distortions, while the remaining 2/3 only raises the average CMB temperature, an effect that is unobservable. At high redshift dissipation is mainly mediated through the quadrupole anisotropies, while after recombination peculiar motions are most important. During recombination the damping of the higher multipoles is also significant. We compute the average distortion for several examples using CosmoTherm, analyzing their dependence on parameters of the primordial power spectrum. For one of the best fit WMAP7 cosmologies, with n_S=1.027 and n_run=-0.034, the cooling of baryonic matter practically compensates the heating from acoustic dissipation in the mu-era. (abridged)Comment: 40 pages, 17 figures, accepted by MNRA