The orbital velocity anisotropy of cluster galaxies: evolution

In nearby clusters early-type galaxies follow isotropic orbits, while the orbits of late-type galaxies are characterized by slightly radial anisotropy. Little is known about the orbits of the different populations of cluster galaxies at redshift above z~0.3. Here we investigate the redshift evolution of the orbits of cluster galaxies using two samples of galaxy clusters spanning similar (evolutionary corrected) mass ranges at different redshifts. The low-redshift (z~0.0-0.1) sample is extracted from the ENACS catalog and the high-redshift (z~0.4-0.8) sample is mostly made of clusters from the EDisCS. For each of these samples, we solve the Jeans equation for hydrostatic equilibrium separately for two cluster galaxy populations, characterized by the presence and, respectively, absence of emission-lines in their spectra ('ELGs' and 'nELGs' hereafter). Using two tracers of the gravitational potential allows to partially break the well known mass-velocity anisotropy degeneracy. We find no significant evolution for the orbits of ELGs. On the other hand the orbits of nELGs do evolve, from radial to isotropic with time. We speculate that this evolution may be driven by the secular mass growth of galaxy clusters during their fast accretion phase. The mass density profiles of the clusters are well fit by NFW models both in the low-z and in the high-z samples. The best-fit NFW concentrations and their redshift evolution are in agreement with the predictions of Lambda CDM cosmological simulations. The evolution of the number density profile of nELGs is opposite to that of the mass density profile, becoming less concentrated with time, probably a result of the transformation of ELGs into nELGs [abridged].Comment: 9 pages, 5 figures. Astr. Ap., 501, 419. Corrected typos in abstract wrt previous versio

SIRNA-Directed In Vivo Silencing of Androgen Receptor Inhibits the Growth of Castration-Resistant Prostate Carcinomas

BACKGROUND: Prostate carcinomas are initially dependent on androgens, and castration or androgen antagonists inhibit their growth. After some time though, tumors become resistant and recur with a poor prognosis. The majority of resistant tumors still expresses a functional androgen receptor (AR), frequently amplified or mutated. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that AR is not only expressed, but is still a key therapeutic target in advanced carcinomas, we injected siRNA targeting AR into mice bearing exponentially growing castration-resistant tumors. Quantification of siRNA into tumors and mouse tissues demonstrated their efficient uptake. This uptake silenced AR in the prostate, testes and tumors. AR silencing in tumors strongly inhibited their growth, and importantly, also markedly repressed the VEGF production and angiogenesis. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that carcinomas resistant to hormonal manipulations still depend on the expression of the androgen receptor for their development in vivo. The siRNA-directed silencing of AR, which allows targeting overexpressed as well as mutated isoforms, triggers a strong antitumoral and antiangiogenic effect. siRNA-directed silencing of this key gene in advanced and resistant prostate tumors opens promising new therapeutic perspectives and tools

Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

BACKGROUND: The liver stages of malaria parasites are inhibited by cytokines such as interferon-gamma or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-alpha possibly because of differences in the models used. We have reassessed the role of TNF-alpha in the different cellular systems used to study the Plasmodium pre-erythrocytic stages. METHODS AND FINDINGS: Human or mouse TNF-alpha were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-alpha treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-alpha inhibition was mediated by a soluble factor present in the supernatant of TNF-alpha stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. CONCLUSIONS: Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Irradiation de l'antimoine dans un microscope électronique à haute tension et observation de boucles de défauts ponctuels

We present the first results of the effects of electron irradiation in (111) thin foils of antimony single crystals (A7 structure) in a high voltage microscope. The voltage which separates the subthreshold events from the bulk radiation damage regime is estimated to be about 725 ± 20 kV. This threshold voltage corresponds to a maximum transferred energy T m of 22.6 eV, and thus to a threshold displacement energy E d of 15.7 or 8.2 eV for the assumed ejection directions or respectively. We have also observed the climbing of dislocations and the agglomeration of point defects into dislocation loops.Nous présentons les premiers résultats concernant l'irradiation électronique de lames monocristallines d'antimoine (structure A7) de plan moyen (111), dans un microscope à haute tension. Nous estimons à 725 ± 20 kV la tension qui sépare le régime d'irradiation sous le seuil du régime d'irradiation proprement dit. Cette tension seuil correspond à une énergie maximale Tm cédée lors d'un choc frontal égale à 22,6 eV, et donc à une énergie seuil de déplacement E d égale respectivement à 15,7 ou 8,2 eV selon que l'on admet que les atomes sont éjectés dans les directions ou . Nous avons également observé la montée des dislocations et la formation de boucles de défauts ponctuels

Correlations between stress and microstructure into LPCVD silicon films

Silicon films have been deposited by low pressure chemical vapour deposition (LPCVD) from silane SiH4 at temperatures and pressures varying respectively from 520°C to 750°C and from 100 mTorr to 300 mTorr. Films residual stresses are studied as a function of deposition parameters (temperature and total pressure). Major stress variations (from compressive to tensile values) are explained through the cumulated influences of the deposition and crystallisation phenomena, evidencing correlations with silicon microstructure (amorphous, semicrystalline, mixed crystalline or polycrystalline) characterised by transmission electron microscopy (TEM) . Finally, residual stress and silicon microstructure are directly related to the ratio between deposition and crystallisation rates, enabling the development of laws for their modelling into silicon films deposited by LPCVD

Irradiation de l'antimoine dans un microscope électronique à haute tension et observation de boucles de défauts ponctuels

Nous présentons les premiers résultats concernant l'irradiation électronique de lames monocristallines d'antimoine (structure A7) de plan moyen (111), dans un microscope à haute tension. Nous estimons à 725 ± 20 kV la tension qui sépare le régime d'irradiation sous le seuil du régime d'irradiation proprement dit. Cette tension seuil correspond à une énergie maximale Tm cédée lors d'un choc frontal égale à 22,6 eV, et donc à une énergie seuil de déplacement E d égale respectivement à 15,7 ou 8,2 eV selon que l'on admet que les atomes sont éjectés dans les directions ou . Nous avons également observé la montée des dislocations et la formation de boucles de défauts ponctuels