| 1. |
- Houard, Aurélien, et al.
(författare)
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Laser-guided lightning
- 2023
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Ingår i: Nature Photonics. - : Springer Nature. - 1749-4885 .- 1749-4893. ; 17:3, s. 231-235
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Tidskriftsartikel (refereegranskat)abstract
- Lightning discharges between charged clouds and the Earth's surface are responsible for considerable damages and casualties. It is therefore important to develop better protection methods in addition to the traditional Franklin rod. Here we present the first demonstration that laser-induced filaments-formed in the sky by short and intense laser pulses-can guide lightning discharges over considerable distances. We believe that this experimental breakthrough will lead to progress in lightning protection and lightning physics. An experimental campaign was conducted on the Santis mountain in north-eastern Switzerland during the summer of 2021 with a high-repetition-rate terawatt laser. The guiding of an upward negative lightning leader over a distance of 50 m was recorded by two separate high-speed cameras. The guiding of negative lightning leaders by laser filaments was corroborated in three other instances by very-high-frequency interferometric measurements, and the number of X-ray bursts detected during guided lightning events greatly increased. Although this research field has been very active for more than 20 years, this is the first field-result that experimentally demonstrates lightning guided by lasers. This work paves the way for new atmospheric applications of ultrashort lasers and represents an important step forward in the development of a laser based lightning protection for airports, launchpads or large infrastructures. A terawatt laser filament is shown to be able to guide lightning over a distance of 50 m in field trials on the Santis mountain in the Swiss Alps.
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| 2. |
- Adelani, David Ifeoluwa, et al.
(författare)
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MasakhaNER: Named Entity Recognition for African Languages
- 2021
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Ingår i: Transactions of the Association for Computational Linguistics. - : MIT Press. - 2307-387X. ; 9, s. 1116-1131
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Tidskriftsartikel (refereegranskat)abstract
- We take a step towards addressing the under-representation of the African continent in NLP research by bringing together different stakeholders to create the first large, publicly available, high-quality dataset for named entity recognition (NER) in ten African languages. We detail the characteristics of these languages to help researchers and practitioners better understand the challenges they pose for NER tasks. We analyze our datasets and conduct an extensive empirical evaluation of state-of-the-art methods across both supervised and transfer learning settings. Finally, we release the data, code, and models to inspire future research on African NLP.
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| 3. |
- Ahmed, Kamran, et al.
(författare)
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Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts
- 2015
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. Materials and methods: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. Results: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement kappa 0.89) and they included: need for a training curriculum (inter-rater agreement kappa 0.85); identification of learning needs (kappa 0.83); development of the curriculum contents (kappa 0.81); an overview of available curricula (kappa 0.79); settings for robotic surgery training ((kappa 0.89); assessment and training of trainers (kappa 0.92); requirements for certification and patient safety (kappa 0.83); and need for a universally standardised curriculum (kappa 0.78). A training curriculum was proposed based on the above discussions. Conclusion: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.
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| 4. |
- Arvizu, Dan, et al.
(författare)
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Summary for Policy Makers: Intergovernmental Panel on Climate Change Special Report Renewable Energy Sources (SRREN)
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The Working Group III Special Report on Renewable Energy Sources and Climate Change Mitigation (SRREN) presents an assessment of the literature on the scientific, technological, environmental, economic and social aspects of the contribution of six renewable energy (RE) sources to the mitigation of climate change. It is intended to provide policy relevant information to governments, intergovernmental processes and other interested parties. This Summary for Policymakers provides an overview of the SRREN, summarizing the essential findings. The SRREN consists of 11 chapters. Chapter 1 sets the context for RE and climate change; Chapters 2 through 7 provide information on six RE technologies, and Chapters 8 through 11 address integrative issues.
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| 5. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 6. |
- Brütt, Katharina, et al.
(författare)
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Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
- 2023
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Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
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Tidskriftsartikel (refereegranskat)abstract
- Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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| 7. |
- Jemth, Ann-Sofie, et al.
(författare)
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Nudix hydrolase 18 catalyzes the hydrolysis of active triphosphate metabolites of the antivirals remdesivir, ribavirin, and molnupiravir
- 2022
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 298:8
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Tidskriftsartikel (refereegranskat)abstract
- Remdesivir and molnupiravir have gained considerable interest because of their demonstrated activity against SARS-CoV-2. These antivirals are converted intracellularly to their active triphosphate forms remdesivir-TP and molnupiravir-TP. Cellular hydrolysis of these active metabolites would consequently decrease the efficiency of these drugs; however, whether endogenous enzymes that can catalyze this hydrolysis exist is unknown. Here, we tested remdesivir-TP as a substrate against a panel of human hydrolases and found that only Nudix hydrolase (NUDT) 18 catalyzed the hydrolysis of remdesivir-TP with notable activity. The kcat/Km value of NUDT18 for remdesivir-TP was determined to be 17,700 s−1M−1, suggesting that NUDT18-catalyzed hydrolysis of remdesivir-TP may occur in cells. Moreover, we demonstrate that the triphosphates of the antivirals ribavirin and molnupiravir are also hydrolyzed by NUDT18, albeit with lower efficiency than Remdesivir-TP. Low activity was also observed with the triphosphate forms of sofosbuvir and aciclovir. This is the first report showing that NUDT18 hydrolyzes triphosphates of nucleoside analogs of exogenous origin, suggesting that NUDT18 can act as a cellular sanitizer of modified nucleotides and may influence the antiviral efficacy of remdesivir, molnupiravir, and ribavirin. As NUDT18 is expressed in respiratory epithelial cells, it may limit the antiviral efficacy of remdesivir and molnupiravir against SARS-CoV-2 replication by decreasing the intracellular concentration of their active metabolites at their intended site of action.
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| 8. |
- Kumpiene, Jurate, et al.
(författare)
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Assessment of zerovalent iron for stabilization of chromium, copper, and arsenic in soil
- 2006
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 144:1, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Stabilization of soil contaminated with trace elements is a remediation practice that does not reduce the total content of contaminants, but lowers the amounts of mobile and bioavailable fractions. This study evaluated the efficiency of Fe(0) to reduce the mobility and bioavailability of Cr, Cu, As and Zn in a chromated copper arsenate (CCA)-contaminated soil using chemical, biochemical and biotoxicity tests. Contaminated soil was stabilized with 1% iron grit. This treatment decreased As and Cr concentrations in leachates (by 98% and 45%, respectively), in soil pore water (by 99% and 94%, respectively) and in plant shoots (by 84% and 95%, respectively). The stabilization technique also restored most of analyzed soil enzyme activities and reduced microbial toxicity, as evaluated by the BioTox test. After stabilization, exchangeable and bioaccessible fractions of Cu remained high, causing some residual toxicity in the treated soil.
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| 9. |
- Michel, Maurice, et al.
(författare)
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Computational and Experimental Druggability Assessment of Human DNA Glycosylases
- 2019
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 4:7, s. 11642-11656
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Tidskriftsartikel (refereegranskat)abstract
- Due to a polar or even charged binding interface, DNA-binding proteins are considered extraordinarily difficult targets for development of small-molecule ligands and only a handful of proteins have been targeted successfully to date. Recently, however, it has been shown that development of selective and efficient inhibitors of 8-oxoguanine DNA glycosylase is possible. Here, we describe the initial druggability assessment of DNA glycosylases in a computational setting and experimentally investigate several methods to target endonuclease VIII-like 1 (NEIL1) with small-molecule inhibitors. We find that DNA glycosylases exhibit good predicted druggability in both DNA-bound and -unbound states. Furthermore, we find catalytic sites to be highly flexible, allowing for a range of interactions and binding partners. One flexible catalytic site was rationalized for NEIL1 and further investigated experimentally using both a biochemical assay in the presence of DNA and a thermal shift assay in the absence of DNA.
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| 10. |
- Visnes, Torkild, et al.
(författare)
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Targeting OGG1 arrests cancer cell proliferation by inducing replication stress
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:21, s. 12234-12251
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Tidskriftsartikel (refereegranskat)abstract
- Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g. 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti-cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause S-phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g. PARP1, as potential targets for cancer treatment.
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