| 1. |
- Au, M., et al.
(författare)
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In-source and in-trap formation of molecular ions in the actinide mass range at CERN-ISOLDE
- 2023
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Ingår i: Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms. - 0168-583X. ; 541, s. 375-379
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Tidskriftsartikel (refereegranskat)abstract
- The use of radioactive molecules for fundamental physics research is a developing interdisciplinary field limited dominantly by their scarce availability. In this work, radioactive molecular ion beams containing actinide nuclei extracted from uranium carbide targets are produced via the Isotope Separation On-Line technique at the CERN-ISOLDE facility. Two methods of molecular beam production are studied: extraction of molecular ion beams from the ion source, and formation of molecular ions from the mass-separated ion beam in a gas-filled radio-frequency quadrupole ion trap. Ion currents of U+, UO1-3+, UC1-3+, UF1-4+, UF1,2O1,2+ are reported. Metastable tantalum and uranium fluoride molecular ions are identified. Formation of UO1-3+, U(OH)1-3+, UC1-3+, UF1,2O1,2+ from mass-separated beams of U+, UF1,2+ with residual gas is observed in the ion trap. The effect of trapping time on molecular formation is presented.
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| 2. |
- Stegemann-Koniszewski, S, et al.
(författare)
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TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection
- 2013
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Ingår i: Journal of innate immunity. - : S. Karger AG. - 1662-8128 .- 1662-811X. ; 5:1, s. 84-96
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Tidskriftsartikel (refereegranskat)abstract
- Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
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| 4. |
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| 5. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 7. |
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| 8. |
- Rothe, S., et al.
(författare)
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Targets and ion sources at CERN-ISOLDE - Facilities and developments
- 2023
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Ingår i: Nuclear Instruments & Methods in Physics Research Section B-Beam Interactions with Materials and Atoms. - 0168-583X. ; 542, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- At the CERN-ISOLDE radioactive ion beam facility, thick targets are irradiated using a beam of 1.4-GeV protons. One of ISOLDE's key features is the large choice of ion source types and target materials available, enabling us to select the ideal combination for optimal intensity and purity of the isotopes requested by ISOLDE users. The ever-increasing demands in terms of isotope production yield, beam purity, and overall reliability of the employed systems are driving the continuous development efforts.Over the past few years, CERN has invested heavily in facilities and infrastructure that facilitate ongoing developments required for ISOLDE. A dedicated offline laboratory (Offline 2) has been recently equipped with high repetition rate nanosecond tunable lasers required for scheme development and developments of specialized laser ion source types such as VADLIS, LIST and PI-LIST. Moreover, it hosts a twin setup of the ISOLDE RFQ cooler and buncher (ISCOOL), which is envisaged to be used for studies of molecular beam creation and breakup, as well as the development of improved RFQ services and operational modes. For material development, particularly for nanostructured materials, the new nano laboratory has just been commissioned and will enable the production and development of nano actinide targets for ISOLDE. In this contribution we describe the infrastructure required for target and ion source developments, highlight recent efforts and experimental results on both target material development and ion source development, and provide an outlook on what to expect in the near future.
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| 9. |
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| 10. |
- Skryabin, Boris, V, et al.
(författare)
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Pervasive head-to-tail insertions of DNA templates mask desired CRISPR-Cas9-mediated genome editing events
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- CRISPR-Cas9-mediated homology-directed DNA repair is the method of choice for precise gene editing in a wide range of model organisms, including mouse and human. Broad use by the biomedical community refined the method, making it more efficient and sequence specific. Nevertheless, the rapidly evolving technique still contains pitfalls. During the generation of six different conditional knockout mouse models, we discovered that frequently (sometimes solely) homology-directed repair and/or nonhomologous end joining mechanisms caused multiple unwanted head-to-tail insertions of donor DNA templates. Disturbingly, conventionally applied PCR analysis, in most cases, failed to identify these multiple integration events, which led to a high rate of falsely claimed precisely edited alleles. We caution that comprehensive analysis of modified alleles is essential and offer practical solutions to correctly identify precisely edited chromosomes.
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