Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens ...shown to induce such protection in humans. Such protection is thought to be mediated by CD8⁺ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8⁺, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we ...examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (
= 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (
= 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (
< 0.01) and relative abundance of bacteria of the Ruminococcaceae family (
< 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
A dynamical classification of the cosmic web Forero–Romero, J. E.; Hoffman, Y.; Gottlöber, S. ...
Monthly notices of the Royal Astronomical Society,
July 2009, Letnik:
396, Številka:
3
Journal Article
Recenzirano
Odprti dostop
In this paper, we propose a new dynamical classification of the cosmic web. Each point in space is classified in one of four possible web types: voids, sheets, filaments and knots. The classification ...is based on the evaluation of the deformation tensor (i.e. the Hessian of the gravitational potential) on a grid. The classification is based on counting the number of eigenvalues above a certain threshold, λth, at each grid point, where the case of zero, one, two or three such eigenvalues corresponds to void, sheet, filament or a knot grid point. The collection of neighbouring grid points, friends of friends, of the same web type constitutes voids, sheets, filaments and knots as extended web objects. A simple dynamical consideration of the emergence of the web suggests that the threshold should not be null, as in previous implementations of the algorithm. A detailed dynamical analysis would have found different threshold values for the collapse of sheets, filaments and knots. Short of such an analysis a phenomenological approach has been opted for, looking for a single threshold to be determined by analysing numerical simulations. Our cosmic web classification has been applied and tested against a suite of large (dark matter only) cosmological N–body simulations. In particular, the dependence of the volume and mass filling fractions on λth and on the resolution has been calculated for the four web types. We also study the percolation properties of voids and filaments. Our main findings are as follows. (i) Already at λth= 0.1 the resulting web classification reproduces the visual impression of the cosmic web. (ii) Between 0.2 ≲λth≲ 0.4, a system of percolated voids coexists with a net of interconnected filaments. This suggests a reasonable choice for λth as the parameter that defines the cosmic web. (iii) The dynamical nature of the suggested classification provides a robust framework for incorporating environmental information into galaxy formation models, and in particular to semi–analytical models.
We present the result of a search of the Milagro sky map for spatial correlations with sources from a subset of the recent Fermi Bright Source List (BSL). The BSL consists of the 205 most significant ...sources detected above 100 MeV by the Fermi Large Area Telescope. We select sources based on their categorization in the BSL, taking all confirmed or possible Galactic sources in the field of view of Milagro. Of the 34 Fermi sources selected, 14 are observed by Milagro at a significance of 3 standard deviations or more. We conduct this search with a new analysis which employs newly optimized gamma-hadron separation and utilizes the full eight-year Milagro data set. Milagro is sensitive to gamma rays with energy from 1 to 100 TeV with a peak sensitivity from 10 to 50 TeV depending on the source spectrum and declination. These results extend the observation of these sources far above the Fermi energy band. With the new analysis and additional data, multi-TeV emission is definitively observed associated with the Fermi pulsar, J2229.0+6114, in the Boomerang pulsar wind nebula (PWN). Furthermore, an extended region of multi-TeV emission is associated with the Fermi pulsar, J0634.0+1745, the Geminga pulsar.
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