| 1. |
- Allaria, E., et al.
(författare)
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Highly coherent and stable pulses from the FERMI seeded free-electron laser in the extreme ultraviolet
- 2012
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Ingår i: Nature Photonics. - 1749-4885. ; 6:10, s. 699-704
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Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers (FELs) are promising devices for generating light with laser-like properties in the extreme ultraviolet and X-ray spectral regions. Recently, FELs based on the self-amplified spontaneous emission (SASE) mechanism have allowed major breakthroughs in diffraction and spectroscopy applications, despite the relatively large shot-to-shot intensity and photon-energy fluctuations and the limited longitudinal coherence inherent in the SASE mechanism. Here, we report results on the initial performance of the FERMI seeded FEL, based on the high-gain harmonic generation configuration, in which an external laser is used to initiate the emission process. Emission from the FERMI FEL-1 source occurs in the form of pulses carrying energy of several tens of microjoules per pulse and tunable throughout the 65 to 20 nm wavelength range, with unprecedented shot-to-shot wavelength stability, low-intensity fluctuations, close to transform-limited bandwidth, transverse and longitudinal coherence and full control of polarization.
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| 2. |
- Barceló, Isabel M., et al.
(författare)
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Role of enzymatic activity in the biological cost associated with the production of ampC b-lactamases in pseudomonas aeruginosa
- 2022
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- In the current scenario of growing antibiotic resistance, understanding the interplay between resistance mechanisms and biological costs is crucial for designing therapeutic strategies. In this regard, intrinsic AmpC β-lactamase hyperproduction is probably themost important resistancemechanismof Pseudomonas aeruginosa, proven to entail important biological burdens that attenuate virulence mostly under peptidoglycan recycling alterations. P. aeruginosa can acquire resistance to new β-lactam-β-lactamase inhibitor combinations (ceftazidime-avibactam and ceftolozane-tazobactam) through mutations affecting ampC and its regulatory genes, but the impact of these mutations on the associated biological cost and the role that β-lactamase activity plays per se in contributing to the above-mentioned virulence attenuation are unknown. The same questions remain unsolved for plasmid-encoded AmpC-type β-lactamases such as FOX enzymes, some of which also provide resistance to new β-lactam-β-lactamase inhibitor combinations. Here, we assessed from different perspectives the effects of changes in the active center and, thus, in the hydrolytic spectrum resistance to inhibitors of AmpC-type β-lactamases on the fitness and virulence of P. aeruginosa, using site-directed mutagenesis; the previously described AmpC variants T96I, G183D, and ΔG229-E247; and, finally, blaFOX-4 versus blaFOX-8. Our results indicate the essential role of AmpC activity per se in causing the reported full virulence attenuation (in terms of growth, motility, cytotoxicity, and Galleria mellonella larvae killing), although the biological cost of the above-mentioned AmpC-type variants was similar to that of the wild-type enzymes. This suggests that there is not an important biological burden that may limit the selection/spread of these variants, which could progressively compromise the future effectiveness of the above-mentioned drug combinations.
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