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| 2. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 4. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 5. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 6. |
- Bakker, D. C. E., et al.
(författare)
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An update to the surface ocean CO2 atlas (SOCAT version 2)
- 2014
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 6:1, s. 69-90
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Tidskriftsartikel (refereegranskat)abstract
- The Surface Ocean CO2 Atlas (SOCAT), an activity of the international marine carbon research community, provides access to synthesis and gridded fCO2 (fugacity of carbon dioxide) products for the surface oceans. Version 2 of SOCAT is an update of the previous release (version 1) with more data (increased from 6.3 million to 10.1 million surface water fCO 2 values) and extended data coverage (from 1968-2007 to 1968-2011). The quality control criteria, while identical in both versions, have been applied more strictly in version 2 than in version 1. The SOCAT website (http://www.socat.info/) has links to quality control comments, metadata, individual data set files, and synthesis and gridded data products. Interactive online tools allow visitors to explore the richness of the data. Applications of SOCAT include process studies, quantification of the ocean carbon sink and its spatial, seasonal, year-to-year and longerterm variation, as well as initialisation or validation of ocean carbon models and coupled climate-carbon models. © Author(s) 2014. CC Attribution 3.0 License.
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| 7. |
- Breitburg, D. L., et al.
(författare)
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And on top of all that…: Coping with ocean acidification in the midst of many stressors by denise
- 2015
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Ingår i: Oceanography. - : The Oceanography Society. - 1042-8275. ; 28:2, s. 48-61
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Tidskriftsartikel (refereegranskat)abstract
- Oceanic and coastal waters are acidifying due to processes dominated in the open ocean by increasing atmospheric CO2 and dominated in estuaries and some coastal waters by nutrient-fueled respiration. The patterns and severity of acidification, as well as its effects, are modified by the host of stressors related to human activities that also influence these habitats. Temperature, deoxygenation, and changes in food webs are particularly important co-stressors because they are pervasive, and both their causes and effects are often mechanistically linked to acidification. Development of a theoretical underpinning to multiple stressor research that considers physiological, ecological, and evolutionary perspectives is needed because testing all combinations of stressors and stressor intensities experimentally is impossible. Nevertheless, use of a wide variety of research approaches is a logical and promising strategy for improving understanding of acidification and its effects. Future research that focuses on spatial and temporal patterns of stressor interactions and on identifying mechanisms by which multiple stressors affect individuals, populations, and ecosystems is critical. It is also necessary to incorporate consideration of multiple stressors into management, mitigation, and adaptation to acidification and to increase public and policy recognition of the importance of addressing acidification in the context of the suite of other stressors with which it potentially interacts. © 2015 by The Oceanography Society. All rights reserved.
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| 9. |
- Baldwin, H, et al.
(författare)
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Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 297-
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Tidskriftsartikel (refereegranskat)abstract
- Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
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| 10. |
- Cooper, Ian R., et al.
(författare)
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Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 26:17, s. 4179-4183
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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