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- Atsawawaranunt, Kamolphat, et al.
(författare)
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The SISAL database : a global resource to document oxygen and carbon isotope records from speleothems
- 2018
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 10:3, s. 1687-1713
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Tidskriftsartikel (refereegranskat)abstract
- Stable isotope records from speleothems provide information on past climate changes, most particularly information that can be used to reconstruct past changes in precipitation and atmospheric circulation. These records are increasingly being used to provide "out-of-sample" evaluations of isotope-enabled climate models. SISAL (Speleothem Isotope Synthesis and Analysis) is an international working group of the Past Global Changes (PAGES) project. The working group aims to provide a comprehensive compilation of speleothem isotope records for climate reconstruction and model evaluation. The SISAL database contains data for individual speleothems, grouped by cave system. Stable isotopes of oxygen and carbon (delta O-18, delta C-13) measurements are referenced by distance from the top or bottom of the speleothem. Additional tables provide information on dating, including information on the dates used to construct the original age model and sufficient information to assess the quality of each data set and to erect a standardized chronology across different speleothems. The metadata table provides location information, information on the full range of measurements carried out on each speleothem and information on the cave system that is relevant to the interpretation of the records, as well as citations for both publications and archived data.
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- Borte, Stephan, et al.
(författare)
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Newborn screening for primary immunodeficiencies: beyond SCID and XLA.
- 2011
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1246, s. 118-30
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Tidskriftsartikel (refereegranskat)abstract
- Primary immunodeficiencies (PID) encompass more than 250 disease entities, including phagocytic disorders, complement deficiencies, T cell defects, and antibody deficiencies. While differing in clinical severity, early diagnosis and treatment is of considerable importance for all forms of PID to prevent organ damage and life-threatening infections. During the past few years, neonatal screening assays have been developed to detect diseases hallmarked by the absence of T or B lymphocytes, classically seen in severe combined immunodeficiencies (SCID) and X-linked agammaglobulinemia (XLA). As described in this review, a reduction or lack of T and B cells in newborns is also frequently found in several other forms of PID, requiring supplemental investigation and involving the development of additional technical platforms in order to help classify abnormal screening results.
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- Comas-Bru, Laia, et al.
(författare)
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Evaluating model outputs using integrated global speleothem records of climate change since the last glacial
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:4, s. 1557-1579
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Tidskriftsartikel (refereegranskat)abstract
- Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data-model comparisons. Here, we illustrate this using 456 globally distributed speleothem delta O-18 records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data-model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on delta O-18 values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.
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- Feng, HL, et al.
(författare)
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Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 930-
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
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- Hepburn, Lucy, et al.
(författare)
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A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
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Tidskriftsartikel (refereegranskat)abstract
- Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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| 12. |
- Isaksson, Mikael, et al.
(författare)
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Partial donor-donor energy migration (PDDEM) : a novel fluorescence method for internal protein distance measurements
- 2004
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6:11, s. 3001-3008
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Tidskriftsartikel (refereegranskat)abstract
- We show that the photophysics of chemically identical but photophysically non-identical fluorescent pairs can be used for measuring distances within proteins. For this purpose, the theory of partial donor-donor energy migration (PDDEM, S. Kalinin, J. G. Molotkovsky and L. B.-Angstrom. Johansson, Spectrochim. Acta, Part A, 2002, 58, 1057-1097) was applied for distance measurements between BODIPY groups covalently linked to cystein residues in plasminogen activator inhibitor of type 2 (PAI-2). Two sulfhydryl specific derivatives of BODIPY were used namely: N-(4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene-2-yl) iodoacetamide and N-(4.4-difluoro-5.7-ditriethyl-4-bona-3a,4a-diaza-s-indacene-3-yl) methyl iodoacetamide. To determine distances, the time-resolved fluorescence relaxation for two singly labelled forms of PAI-2, as well as the corresponding doubly labelled protein were combined and analysed in a global manner. Fluorescence depolarisation experiments on the labelled mutants were also analysed. The distances determined by PDDEM were in good agreement to those obtained from donor-donor energy migration (DDEM) experiments and structural data on PAI-2. The PDDEM approach allows for the use of very different fluorescent probes, which enables wide range of distances to be measured. The PDDEM model also provides a rational explanation to why previous observations of polyfluorophore-labelled proteins exhibit a shorter average fluorescence lifetime compared to the arithmetic average of lifetimes obtained for the corresponding single labelled proteins.
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- Ny, Lars, 1967, et al.
(författare)
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BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis.
- 2020
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 59:7, s. 833-844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies.Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09-1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I-III melanoma (combined HR: 1.16, 95% CI: 0.92-1.46), and on PFS in stage III-IV (HR: 0.98 (95% CI: 0.68-1.40)).Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.
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