| 2. |
- Broiles, Thomas W., et al.
(författare)
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Statistical analysis of suprathermal electron drivers at 67P/Churyumov-Gerasimenko
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S312-S322
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Tidskriftsartikel (refereegranskat)abstract
- We use observations from the Ion and Electron Sensor (IES) on board the Rosetta spacecraft to study the relationship between the cometary suprathermal electrons and the drivers that affect their density and temperature. We fit the IES electron observations with the summation of two kappa distributions, which we characterize as a dense and warm population (similar to 10 cm(-3) and similar to 16 eV) and a rarefied and hot population (similar to 0.01 cm(-3) and similar to 43 eV). The parameters of our fitting technique determine the populations' density, temperature, and invariant kappa index. We focus our analysis on the warm population to determine its origin by comparing the density and temperature with the neutral density and magnetic field strength. We find that the warm electron population is actually two separate sub-populations: electron distributions with temperatures above 8.6 eV and electron distributions with temperatures below 8.6 eV. The two sub-populations have different relationships between their density and temperature. Moreover, the two sub-populations are affected by different drivers. The hotter sub-population temperature is strongly correlated with neutral density, while the cooler sub-population is unaffected by neutral density and is only weakly correlated with magnetic field strength. We suggest that the population with temperatures above 8.6 eV is being heated by lower hybrid waves driven by counterstreaming solar wind protons and newly formed, cometary ions created in localized, dense neutral streams. To the best of our knowledge, this represents the first observations of cometary electrons heated through wave-particle interactions.
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| 3. |
- Felgner, S, et al.
(författare)
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aroA-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant
- 2016
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Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant attenuated Salmonella enterica serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of aroA, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of aroA dramatically increased the virulence of attenuated Salmonella in mouse models. Mutant bacteria lacking aroA elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) after systemic application. A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that Delta aroA mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of aroA affected flagellin phase variation and gene expression of the virulence-associated genes arnT and ansB. Finally, Delta aroA strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of Delta aroA-attenuated Salmonella for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine. IMPORTANCE Recombinant attenuated bacterial vector systems based on genetically engineered Salmonella have been developed as highly potent vaccines. Due to the pathogenic properties of Salmonella, efficient attenuation is required for clinical applications. Since the hallmark study by Hoiseth and Stocker in 1981 (S. K. Hoiseth and B. A. D. Stocker, Nature 291:238-239, 1981, http://dx.doi.org/10.1038/291238a0), the auxotrophic Delta aroA mutation has been generally considered safe and universally used to attenuate bacterial strains. Here, we are presenting the remarkable finding that a deletion of aroA leads to pronounced alterations of gene expression, metabolism, and cellular physiology, which resulted in increased immunogenicity, virulence, and adjuvant potential of Salmonella. These results suggest that the enhanced immunogenicity of aroA-deficient Salmonella strains might be advantageous for optimizing bacterial vaccine carriers and immunotherapy. Accordingly, we demonstrate a superior performance of Delta aroA Salmonella in bacterium-mediated tumor therapy. In addition, the present study highlights the importance of a functional shikimate pathway to sustain bacterial physiology and metabolism.
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