| 1. |
- de Jong, R. S., et al.
(författare)
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4MOST : Project overview and information for the First Call for Proposals
- 2019
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Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
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| 2. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 3. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 4. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 5. |
- Bryant, J. M., et al.
(författare)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
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Tidskriftsartikel (refereegranskat)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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| 6. |
- Aguado, D. S., et al.
(författare)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 7. |
- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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| 8. |
- Schultheis, M., et al.
(författare)
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Baade's window and APOGEE Metallicities, ages, and chemical abundances
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
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Tidskriftsartikel (refereegranskat)abstract
- Context. Baade's window (BW) is one of the most observed Galactic bulge fields in terms of chemical abundances. Owing to its low and homogeneous interstellar absorption it is considered the perfect calibration field for Galactic bulge studies. Aims. In the era of large spectroscopic surveys, calibration fields such as BW are necessary for cross calibrating the stellar parameters and individual abundances of the APOGEE survey. Methods. We use the APOGEE BW stars to derive the metallicity distribution function (MDF) and individual abundances for alpha- and iron-peak elements of the APOGEE ASPCAP pipeline (DR13), as well as the age distribution for stars in BW. Results. We determine the MDF of APOGEE stars in BW and find a remarkable agreement with that of the Gaia-ESO survey (GES). Both exhibit a clear bimodal distribution. We also find that the Mg-metallicity planes of the two surveys agree well, except for the metal-rich part ([Fe/H] > 0.1), where APOGEE finds systematically higher Mg abundances with respect to the GES. The ages based on the [C/N] ratio reveal a bimodal age distribution, with a major old population at similar to 10 Gyr, with a decreasing tail towards younger stars. A comparison of stellar parameters determined by APOGEE and those determined by other sources reveals detectable systematic offsets, in particular for spectroscopic surface gravity estimates. In general, we find a good agreement between individual abundances of O,Na, Mg, Al, Si, K, Ca, Cr, Mn, Co, and Ni from APOGEE with that of literature values. Conclusions. We have shown that in general APOGEE data show a good agreement in terms of MDF and individual chemical abundances with respect to literature works. Using the [C/N] ratio we found a significant fraction of young stars in BW.
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| 9. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 10. |
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| 11. |
- Makita, M., et al.
(författare)
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Femtosecond phase-transition in hard x-ray excited bismuth
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of bismuth crystal structure upon excitation of its A(1g) phonon has been intensely studied with short pulse optical lasers. Here we present the first-time observation of a hard x-ray induced ultrafast phase transition in a bismuth single crystal at high intensities (similar to 10(14) W/cm(2)). The lattice evolution was followed using a recently demonstrated x-ray single-shot probing setup. The time evolution of the (111) Bragg peak intensity showed strong dependence on the excitation fluence. After exposure to a sufficiently intense x-ray pulse, the peak intensity dropped to zero within 300 fs, i.e. faster than one oscillation period of the A(1g) mode at room temperature. Our analysis indicates a nonthermal origin of a lattice disordering process, and excludes interpretations based on electron-ion equilibration process, or on thermodynamic heating process leading to plasma formation.
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| 12. |
- Chatziioannou, Aristotelis, et al.
(författare)
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Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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| 13. |
- Fang, Jun, et al.
(författare)
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Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
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| 14. |
- Salomonsson, A., et al.
(författare)
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A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer
- 2018
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S431-S432
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.Method: Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients' medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].Result: In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.Conclusion: SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.
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| 15. |
- Saxholm, S., et al.
(författare)
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Development of measurement and calibration techniques for dynamic pressures and temperatures (DynPT) : Background and objectives of the 17IND07 DynPT project in the European Metrology Programme for Innovation and Research (EMPIR)
- 2018
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Ingår i: Journal of Physics. - : Institute of Physics Publishing.
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Konferensbidrag (refereegranskat)abstract
- This project has five specific objectives: To provide traceability for dynamic pressure and temperature through development of measurement standards and validated calibration procedures; To quantify the effects of influencing quantities on the response of dynamic pressure and temperature sensors, in order to determine the appropriate calibration procedures and measurement uncertainties for industrial measurements; To develop new measurement methods and sensors for measuring dynamic pressure and temperature in demanding industrial applications, and to demonstrate the improved accuracy and reliability obtained with those; To validate all of the methods and sensors developed in this project through demonstrations in selected industrial applications; and To ensure by close engagement with industry, that the developed calibration and measurement techniques and technology are adopted by them. The challenge is that in many industrial applications pressure and temperature measurements are performed under dynamically changing conditions. The aim of this project is to improve the accuracy and reliability of pressure and temperature measurements in these challenging conditions. A European joint research project named Development of measurement and calibration techniques for dynamic pressures and temperatures (shortname DynPT) started in the summer 2018.
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| 16. |
- Souto, D., et al.
(författare)
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Chemical Abundances of M-Dwarfs from the Apogee Survey. I. The Exoplanet Hosting Stars Kepler-138 and Kepler-186
- 2017
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 835:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detailed chemical abundance analysis of the exoplanet-hosting M-dwarf stars Kepler-138 and Kepler-186 from the analysis of high-resolution (R similar to 22,500) H-band spectra from the SDSS-IV-APOGEE survey. Chemical abundances of 13 elements-C, O, Na, Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, and Fe-are extracted from the APOGEE spectra of these early M-dwarfs via spectrum syntheses computed with an improved line list that takes into account H2O and FeH lines. This paper demonstrates that APOGEE spectra can be analyzed to determine detailed chemical compositions of M-dwarfs. Both exoplanet-hosting M-dwarfs display modest sub-solar metallicities: [Fe/H](Kepler-138) = -0.09 +/- 0.09 dex and [Fe/H](Kepler-186) = -0.08 +/- 0.10 dex. The measured metallicities resulting from this high-resolution analysis are found to be higher by similar to 0.1-0.2 dex than previous estimates from lower-resolution spectra. The C/O ratios obtained for the two planet-hosting stars are near-solar, with values of 0.55 +/- 0.10 for Kepler-138 and 0.52 +/- 0.12 for Kepler-186. Kepler-186 exhibits a marginally enhanced [Si/Fe] ratio.
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| 17. |
- van der Wouden, C. H., et al.
(författare)
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Implementing Pharmacogenomics in Europe : Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium
- 2017
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 101:3, s. 341-358
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Tidskriftsartikel (refereegranskat)abstract
- Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multi-healthcare system approach.
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| 18. |
- Weinberg, David H., et al.
(författare)
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Chemical Cartography with APOGEE : Multi-element Abundance Ratios
- 2019
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 874:1
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Tidskriftsartikel (refereegranskat)abstract
- We map the trends of elemental abundance ratios across the Galactic disk, spanning R = 3-15 kpc and midplane distance vertical bar Z vertical bar = 0-2 kpc, for 15 elements in a sample of 20,485 stars measured by the SDSS/APOGEE survey (O, Na, Mg, Al, Si, P, S, K, Ca, V, Cr, Mn, Fe, Co, Ni). Adopting Mg rather than Fe as our reference element, and separating stars into two populations based on [Fe/Mg], we find that the median trends of [X/Mg] versus [Mg/H] in each population are nearly independent of location in the Galaxy. The full multi-element cartography can be summarized by combining these nearly universal median sequences with our measured metallicity distribution functions and the relative proportions of the low-[Fe/Mg] (high-alpha) and high-[Fe/Mg] (low-alpha) populations, which depend strongly on R and vertical bar Z vertical bar. We interpret the median sequences with a semi-empirical "two-process" model that describes both the ratio of core collapse and Type Ia supernova (SN Ia) contributions to each element and the metallicity dependence of the supernova yields. These observationally inferred trends can provide strong tests of supernova nucleosynthesis calculations. Our results lead to a relatively simple picture of abundance ratio variations in the Milky Way, in which the trends at any location can be described as the sum of two components with relative contributions that change systematically and smoothly across the Galaxy. Deviations from this picture and future extensions to other elements can provide further insights into the physics of stellar nucleosynthesis and unusual events in the Galaxy's history.
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| 19. |
- Winter, C, et al.
(författare)
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Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 27:8, s. 8-1532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear.PATIENTS AND METHODS: Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden.RESULTS: Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years).CONCLUSIONS: In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.
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| 20. |
- Hampe, C. S., et al.
(författare)
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Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform : relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus
- 2019
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 36:11, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate whether the N‐terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform.Methods: GAD65 antibody‐positive healthy individuals (n=13), people with stiff‐person syndrome (n=15) and children with new‐onset Type 1 diabetes (n=654) were analysed to determine binding to full‐length GAD65 and the N‐terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full‐length GAD65/N‐terminal truncated GAD65.Results: The N‐terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab‐positive people with stiff‐person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N‐terminal truncated GAD65 isoform compared to full‐length GAD65. Finally, an N‐terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02).Conclusions: In people with stiff person syndrome preferred binding to the full‐length GAD65 isoform over the N‐terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N‐terminal truncated molecule. These findings support the notion of disease‐specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.
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| 21. |
- Jönsson, A C, et al.
(författare)
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Secondary prevention and lifestyle indices after stroke in a long-term perspective
- 2018
-
Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; , s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe the long-term perspective regarding prevalence of risk factors, secondary stroke prevention, and lifestyle indices after stroke.METHODS: From a population-based one-year cohort (n = 416), we performed an observational study of 145 survivors at 16 months and 10 years after stroke (age 27-97 years) regarding secondary prevention including reaching acceptable treatment goals; nutritional status with focus on underweight; and the lifestyle indices: living situation, level of dependence, and self-assessed health condition.RESULTS: Ten years after stroke, 50% of the subjects with hypertension diagnosis and 55% of those without hypertension diagnosis were within the blood pressure goal <140/90 compared with 32% (P = .008) and 37% (N.S.) at 16 months. Acceptable HbA1c levels among subjects with diabetes mellitus diagnosis increased from 35% to 45% (N.S.). Among those without diabetes diagnosis, satisfactory HbA1c levels decreased from 98% to 79% (P < .001). Underweight increased from 9% to 17% (P = .019). Among patients with cerebral infarction, the prevalence of atrial fibrillation increased from 22% to 29% (P = .004), and treatment with oral anticoagulants from 75% to 78% (N.S.). Acceptable LDL cholesterol levels increased from 59% to 80% (P = .033) among subjects on lipid lowering treatment, and from 18% to 40% among untreated (P = .010). At 10 years, 90% still lived in their own home. Health condition was reported as good/very good/excellent by 65%. Age, female sex, and living situation were associated with intensity of secondary prevention measures and underweight.CONCLUSIONS: The proportion of individuals within treatment goals improved over time, but secondary prevention still needed additional consideration 10 years after stroke.
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| 22. |
- Pinsonneault, Marc H., et al.
(författare)
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The Second APOKASC Catalog : The Empirical Approach
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 239:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a catalog of stellar properties for a large sample of 6676 evolved stars with Apache Point Observatory Galactic Evolution Experiment spectroscopic parameters and Kepler asteroseismic data analyzed using five independent techniques. Our data include evolutionary state, surface gravity, mean density, mass, radius, age, and the spectroscopic and asteroseismic measurements used to derive them. We employ a new empirical approach for combining asteroseismic measurements from different methods, calibrating the inferred stellar parameters, and estimating uncertainties. With high statistical significance, we find that asteroseismic parameters inferred from the different pipelines have systematic offsets that are not removed by accounting for differences in their solar reference values. We include theoretically motivated corrections to the large frequency spacing (Av) scaling relation, and we calibrate the zero-point of the frequency of the maximum power (vmax) relation to be consistent with masses and radii for members of star clusters. For most targets, the parameters returned by different pipelines are in much better agreement than would be expected from the pipeline-predicted random errors, but 22% of them had at least one method not return a result and a much larger measurement dispersion. This supports the usage of multiple analysis techniques for asteroseismic stellar population studies. The measured dispersion in mass estimates for fundamental calibrators is consistent with our error model, which yields median random and systematic mass uncertainties for RGB stars of order 4%. Median random and systematic mass uncertainties are at the 9% and 8% level, respectively, for red clump stars.
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| 23. |
- Zasowski, G., et al.
(författare)
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APOGEE DR14/DR15 Abundances in the Inner Milky Way
- 2019
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 870:2
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Tidskriftsartikel (refereegranskat)abstract
- We present an overview of the distributions of 11 elemental abundances in the Milky Way's (MW) inner regions, as traced by APOGEE stars released as part of the Sloan Digital Sky Survey Data Release. 14/15 (DR14/DR15), including O, Mg, Si, Ca, Cr, Mn, Co, Ni, Na, Al, and K. This sample spans similar to 4000 stars with R-GC <= 4.0 kpc, enabling the most comprehensive study to date of these abundances and their variations within the innermost few kiloparsecs of the MW. We describe the observed abundance patterns ([X/Fe]-[Fe/H]), compare to previous literature results and to patterns in stars at the solar Galactocentric radius (R-GC), and discuss possible trends with DR14/DR15 effective temperatures. We find that the position of the [Mg/Fe]-[Fe/H] "knee" is nearly constant with R-GC, indicating a well-mixed star-forming medium or high levels of radial migration in the early inner Galaxy. We quantify the linear correlation between pairs of elements in different subsamples of stars and find that these relationships vary; some abundance correlations are very similar between the alpha-rich and alpha-poor stars, but others differ significantly, suggesting variations in the metallicity dependencies of certain supernova yields. These empirical trends will form the basis for more detailed future explorations and for the refinement of model comparison metrics. That the inner MW abundances appear dominated by a single chemical evolutionary track and that they extend to such high metallicities underscore the unique importance of this part of the Galaxy for constraining the ingredients of chemical evolution modeling and for improving our understanding of the evolution of the Galaxy as a whole.
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| 24. |
- Artomov, Mykyta, et al.
(författare)
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Rare variant, gene-based association study of hereditary melanoma using whole-exome sequencing
- 2017
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 109:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM). Methods: Using 11 990 jointly processed individual DNA samples, whole-exome sequencing was performed, followed by largescale joint variant calling using GATK (Genome Analysis ToolKit). PLINK/SEQ was used for statistical analysis of genetic variation. Fourmodels were used to estimate the association among different types of variants. In vitro functional validation was performed using three humanmelanoma cell lines in 2D and 3D proliferation assays. In vivo tumor growth was assessed using xenografts of humanmelanoma A375melanoma cells in nudemice (eightmice per group). All statistical tests were two-sided. Results: Strong signals were detected for CDKN2A (Pmin = 6.16×10-8) in the CM cohort (n=273) and BAP1 (Pmin = 3.83×10-6) in the OM (n=99) cohort. Eleven genes that exhibited borderline association (P < 10-4) were independently validated using The Cancer Genome Atlas melanoma cohort (379 CM, 47 OM) and a matched set of 3563 European controls with CDKN2A (P = .009), BAP1 (P = .03), and EBF3 (P = 4.75×10-4), a candidate risk locus, all showing evidence of replication. EBF3 was then evaluated using germline data from a set of 132 familial melanoma cases and 4769 controls of UK origin (joint P = 1.37×10-5). Somatically, loss of EBF3 expression correlated with progression, poorer outcome, and high MITF tumors. Functionally, induction of EBF3 in melanoma cells reduced cell growth in vitro, retarded tumor formation in vivo, and reduced MITF levels. Conclusions: The results of this large rare variant germline association study further define the mutational landscape of hereditary melanoma and implicate EBF3 as a possible CM predisposition gene.
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| 25. |
- Covaci, Adrian, et al.
(författare)
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Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.
- 2015
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 141:Oct 13, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300mg/L or above 3000mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.
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| 26. |
- Fernandes, Ricardo A., et al.
(författare)
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A cell topography-based mechanism for ligand discrimination by the T cell receptor
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:28, s. 14002-14010
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Tidskriftsartikel (refereegranskat)abstract
- The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.
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| 27. |
- Jönsson, L., et al.
(författare)
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Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours
- 2018
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Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. Results: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22–37 mm were detectable in the 111In-SPECT images and spheres larger than 13–22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. Conclusions: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.
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| 28. |
- Masseron, T., et al.
(författare)
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Homogeneous analysis of globular clusters from the APOGEE survey with the BACCHUS code
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 622
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: We seek to provide abundances of a large set of light and neutron-capture elements homogeneously analyzed that cover a wide range of metallicity to constrain globular cluster (GC) formation and evolution models.Methods: We analyzed a large sample of 885 GCs giants from the SDSS IV-Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. We used the Cannon results to separate the red giant branch and asymptotic giant branch stars, not only allowing for a refinement of surface gravity from isochrones, but also providing an independent H-band spectroscopic method to distinguish stellar evolutionary status in clusters. We then used the Brussels Automatic Code for Characterizing High accUracy Spectra (BACCHUS) to derive metallicity, microturbulence, macroturbulence, many light-element abundances, and the neutron-capture elements Nd and Ce for the first time from the APOGEE GCs data.Results: Our independent analysis helped us to diagnose issues regarding the standard analysis of the APOGEE DR14 for low-metallicity GC stars. Furthermore, while we confirm most of the known correlations and anticorrelation trends (Na-O, Mg-Al, C-N), we discover that some stars within our most metal-poor clusters show an extreme Mg depletion and some Si enhancement. At the same time, these stars show some relative Al depletion, displaying a turnover in the Mg-Al diagram. These stars suggest that Al has been partially depleted in their progenitors by very hot proton-capture nucleosynthetic processes. Furthermore, we attempted to quantitatively correlate the spread of Al abundances with the global properties of GCs. We find an anticorrelation of the Al spread against clusters metallicity and luminosity, but the data do not allow us to find clear evidence of a dependence of N against metallicity in the more metal-poor clusters.Conclusions: Large and homogeneously analyzed samples from ongoing spectroscopic surveys unveil unseen chemical details for many clusters, including a turnover in the Mg-Al anticorrelation, thus yielding new constrains for GCs formation/evolution models.
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| 29. |
- Newell, Felicity, et al.
(författare)
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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity of comprehensive mutation data on this rare tumor type. To better understand the genomic landscape of mucosal melanoma, here we describe whole genome sequencing analysis of 67 tumors and validation of driver gene mutations by exome sequencing of 45 tumors. Tumors have a low point mutation burden and high numbers of structural variants, including recurrent structural rearrangements targeting TERT, CDK4 and MDM2. Significantly mutated genes are NRAS, BRAF, NF1, KIT, SF3B1, TP53, SPRED1, ATRX, HLA-A and CHD8. SF3B1 mutations occur more commonly in female genital and anorectal melanomas and CTNNB1 mutations implicate a role for WNT signaling defects in the genesis of some mucosal melanomas. TERT aberrations and ATRX mutations are associated with alterations in telomere length. Mutation profiles of the majority of mucosal melanomas suggest potential susceptibility to CDK4/6 and/or MEK inhibitors.
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| 30. |
- Siedler, S., et al.
(författare)
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Development of a Bacterial Biosensor for Rapid Screening of Yeast p-Coumaric Acid Production
- 2017
-
Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 6:10, s. 1860-1869
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factor-based biosensors are used to identify producer strains, a critical bottleneck in cell factory engineering. Here, we address two challenges with this methodology: transplantation of heterologous transcriptional regulators into new hosts to generate functional biosensors and biosensing of the extracellular product concentration that accurately reflects the effective cell factory production capacity. We describe the effects of different translation initiation rates on the dynamic range of a p-coumaric acid biosensor based on the Bacillus subtilis transcriptional repressor PadR by varying its ribosomal binding site. Furthermore, we demonstrate the functionality of this p-coumaric acid biosensor in Escherichia coli and Corynebacterium glutamicum. Finally, we encapsulate yeast p-coumaric acid-producing cells with E. coli-biosensing cells in picoliter droplets and, in a microfluidic device, rapidly sort droplets containing yeast cells producing high amounts of extracellular p-coumaric acid using the fluorescent E. coli biosensor signal. As additional biosensors become available, such approaches will find broad applications for screening of an extracellular product.
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| 31. |
- Souto, Diogo, et al.
(författare)
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Chemical Abundances of Main-sequence, Turnoff, Subgiant, and Red Giant Stars from APOGEE Spectra. I. Signatures of Diffusion in the Open Cluster M67
- 2018
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 857:1
-
Tidskriftsartikel (refereegranskat)abstract
- Detailed chemical abundance distributions for 14 elements are derived for eight high-probability stellar members of the solar metallicity old open cluster M67 with an age of similar to 4 Gyr. The eight stars consist of four pairs, with each pair occupying a distinct phase of stellar evolution: two G dwarfs, two turnoff stars, two G subgiants, and two red clump (RC) K giants. The abundance analysis uses near-IR high-resolution spectra (lambda 1.5-1.7 mu m) from the Apache Point Observatory Galactic Evolution Experiment survey and derives abundances for C, N, O, Na, Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, and Fe. Our derived stellar parameters and metallicity for 2M08510076+1153115 suggest that this star is a solar twin, exhibiting abundance differences relative to the Sun of <= 0.04 dex for all elements. Chemical homogeneity is found within each class of stars (similar to 0.02 dex), while significant abundance variations (similar to 0.05-0.20 dex) are found across the different evolutionary phases; the turnoff stars typically have the lowest abundances, while the RCs tend to have the largest. Non-LTE corrections to the LTE-derived abundances are unlikely to explain the differences. A detailed comparison of the derived Fe, Mg, Si, and Ca abundances with recently published surface abundances from stellar models that include chemical diffusion provides a good match between the observed and predicted abundances as a function of stellar mass. Such agreement would indicate the detection of chemical diffusion processes in the stellar members of M67.
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| 32. |
- Souto, Diogo, et al.
(författare)
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Chemical Abundances of Main-sequence, Turnoff, Subgiant, and Red Giant Stars from APOGEE Spectra. II. Atomic Diffusion in M67 Stars
- 2019
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 874:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chemical abundances for 15 elements (C, N, O, Na, Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, Fe, and Ni) are presented for 83 stellar members of the 4 Gyr old solar-metallicity open cluster M67. The sample contains stars spanning a wide range of evolutionary phases, from G dwarfs to red clump stars. The abundances were derived from near-IR (lambda 1.5-1.7 mu m) high-resolution spectra (R = 22,500) from the SDSS-IV/Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. A 1D local thermodynamic equilibrium abundance analysis was carried out using the APOGEE synthetic spectral libraries, via chi(2) minimization of the synthetic and observed spectra with the qASPCAP code. We found significant abundance differences (similar to 0.05-0.30 dex) between the M67 member stars as a function of the stellar mass (or position on the Hertzsprung-Russell diagram), where the abundance patterns exhibit a general depletion (in [X/H]) in stars at the main-sequence turnoff. The amount of the depletion is different for different elements. We find that atomic diffusion models provide, in general, good agreement with the abundance trends for most chemical species, supporting recent studies indicating that measurable atomic diffusion operates in M67 stars.
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| 33. |
- Vågberg, Mattias, et al.
(författare)
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Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society
- 2017
-
Ingår i: Acta Neurologica Scandinavica. - Hoboken, USA : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 135:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.
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| 34. |
- Anguiano, B., et al.
(författare)
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Comprehensive comparison between APOGEE and LAMOST Radial velocities and atmospheric stellar parameters
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
-
Tidskriftsartikel (refereegranskat)abstract
- Context. In the era of massive spectroscopy surveys, automated stellar parameter pipelines and their validation are extremely important for an efficient scientific exploitation of the spectra. Aims. We undertake a critical and comprehensive comparison of the radial velocities and the main stellar atmosphere parameters for stars in common between the latest data releases from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE) and the Large sky Area Multi-Object Spectroscopic Telescope (LAMOST) surveys. Methods. APOGEE is a high-resolution (R = 22500) spectroscopic survey with high signal-to-noise ratio that is part of the Sloan Digital Sky Survey (SDSS). The latest data release, SDSS DR14, comprises APOGEE spectra for 263 444 stars, together with main stellar parameters and individual abundances for up to 20 chemical species. LAMOST is a low-resolution (R = 1800) optical spectroscopic survey also in the Northern Hemisphere, where 4000 fibers can be allocated simultaneously. LAMOST DR3 contains 3 177 995 stars. Results. A total of 42 420 dwarfs and giants stars are in common between the APOGEE DR14 - LAMOST DR3 stellar catalogs. A comparison between APOGEE and LAMOST RVs shows a clear offset of 4.54 +/- 0.03 km s(-1), with a dispersion of 5.8 km s(-1), in the sense that APOGEE radial velocities are higher. We observe a small offset in the effective temperatures of about 13 K, with a scatter of 155 K. A small offset in [Fe/H] of about 0.06 dex together with a scatter of 0.13 dex is also observed. We note that the largest offset between the surveys occurs in the surface gravities. Using only surface gravities in calibrated red giants from APOGEE DR14, with which there are 24 074 stars in common, a deviation of 0.14 dex is found with substantial scatter (0.25 dex). There are 17 482 red giant stars in common between APOGEE DR14 and those in LAMOST tied to APOGEE DR12 via the code called the Cannon. There is generally good agreement between the two data-sets. However, we find that the differences in the stellar parameters depend on effective temperature. For metal-rich stars, a different trend for the [Fe/H] discrepancies is found. Surprisingly, we see no correlation between the internal APOGEE DR14 - DR12 differences in T-eff and those in DR14 - LAMOST tied to DR12, where a correlation should be expected since LAMOST has been calibrated to APOGEE DR12. We find no correlation either between the [Fe/H] discrepancies, suggesting that LAMOST/Cannon is not well coupled to the APOGEE DR12 stellar parameter scale. An [Fe/H] dependence between the stellar parameters in APOGEE DR12 and those in DR14 is reported. We find a weak correlation in the differences between APOGEE DR14 - DR12 and LAMOST on DR12 surface gravity for stars hotter than 4800 K and in the log g range between 2.0 and 2.8 dex. We do not observe an [Fe/H] dependency in the gravity discrepancies.
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| 35. |
- Berge, T. L L, et al.
(författare)
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Bisphenol A concentration in human saliva related to dental polymer-based fillings
- 2017
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Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 21:8, s. 2561-2568
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims of this study were to quantify salivary concentrations of bisphenol A (BPA) and to assess if presence of dental composite fillings is associated with higher BPA levels in saliva. Materials and methods: Twenty individuals with six or more tooth surfaces filled with polymer-based dental materials (composite group) and 20 individuals without any polymer-based materials (control group) were included in the study. Saliva was collected in polypropylene tubes and stored at −80 °C before analysis. Concentration of free (unconjugated) and total bisphenol A was determined by liquid chromatography/mass spectrometry (LC/MS). Values below limit of detection (0.1 ng/mL) were set to one-half of the limit of detection. Mann-Whitney U test (one sided; the Exact Tests Option in IBM-SPSS version 21) was used for the statistical analyses. Results: The concentration of BPA in saliva was very low. In the composite group, 8 of 20 samples had detectable concentrations of BPA. In the control group, 3 of 20 samples had detectable concentrations of BPA. Statistical analysis indicated that the concentration of unconjugated BPA was slightly higher in the composite group (p = 0.044) than in the control group. Conclusions: Presence of dental composites may be associated with slightly higher concentration of unconjugated BPA in saliva. However, additional studies using sensitive analytical methods are needed before firm conclusions can be drawn. Influence from other factors, like food intake and time of the day for saliva sampling, must be considered. Clinical relevance: The relative contribution of existing polymer-based dental fillings to total BPA exposure seems to be low.
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| 36. |
- Briat, C., et al.
(författare)
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The Conservation of Information, Towards an Axiomatized Modular Modeling Approach to Congestion Control
- 2015
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Ingår i: IEEE/ACM Transactions on Networking. - 1063-6692 .- 1558-2566. ; 23:3, s. 851-865
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Tidskriftsartikel (refereegranskat)abstract
- We derive a modular fluid-flow network congestion control model based on a law of fundamental nature in networks: the conservation of information. Network elements such as queues, users, and transmission channels and network performance indicators like sending/acknowledgment rates and delays are mathematically modeled by applying this law locally. Our contributions are twofold. First, we introduce a modular metamodel that is sufficiently generic to represent any network topology. The proposed model is composed of building blocks that implement mechanisms ignored by the existing ones, which can be recovered from exact reduction or approximation of this new model. Second, we provide a novel classification of previously proposed models in the literature and show that they are often not capable of capturing the transient behavior of the network precisely. Numerical results obtained from packet-level simulations demonstrate the accuracy of the proposed model.
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| 37. |
- Delavaran, H, et al.
(författare)
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Cognitive function in stroke survivors : A 10-year follow-up study
- 2017
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 136:3, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Post-stroke cognitive impairment (PSCI) has considerable impact on patients and society. However, long-term studies on PSCI are scarce and may be influenced by assessment methods and selection bias. We aimed to (i) assess the prevalence of long-term PSCI; (ii) compare two common cognitive assessment instruments; and (iii) compare cognitive function of long-term stroke survivors with non-stroke persons.METHODS: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered to 10-year survivors from a population-based cohort of first-ever stroke patients included in the Lund Stroke Register, Sweden, in 2001-2002. PSCI was defined as MMSE<27 and/or MoCA<25 and severe cognitive impairment as MMSE<23. Age- and sex-matched non-stroke control subjects who had performed MMSE (but not MoCA) were recruited from the longitudinal population study "Good Ageing in Skåne." The odds of having cognitive impairment for stroke survivors compared to controls were examined with logistic regression analyses adjusting for education.RESULTS: Of 145 stroke survivors after 10 years, 127 participated. MMSE showed PSCI in 46%, whereas MoCA displayed PSCI in 61%. Among the stroke survivors with MoCA<25, 35% had MMSE≥27 (P<.001). The odds of having severe cognitive impairment defined as MMSE<23 were higher among the stroke survivors compared to 354 controls (education-adjusted; OR=2.5; P=.004).CONCLUSIONS: Post-stroke cognitive impairment was prevalent among 10-year stroke survivors, and the odds of having severe cognitive impairment were higher among the stroke survivors compared to non-stroke persons. The burden of long-term PSCI might have been underestimated previously, and MoCA may be more suitable than MMSE to detect long-term PSCI.
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| 38. |
- Megretski, A., et al.
(författare)
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Integral Quadratic Constraints
- 2018
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Ingår i: The Control Handbook. - : CRC Press. ; , s. 41-1-41-20, s. 1-20
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 39. |
- Monteseguro, V, et al.
(författare)
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Phase stability and electronic structure of iridium metal at the megabar range
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The 5d transition metals have attracted specific interest for high-pressure studies due to their extraordinary stability and intriguing electronic properties. In particular, iridium metal has been proposed to exhibit a recently discovered pressure-induced electronic transition, the so-called core-level crossing transition at the lowest pressure among all the 5d transition metals. Here, we report an experimental structural characterization of iridium by x-ray probes sensitive to both long- and short-range order in matter. Synchrotron-based powder x-ray diffraction results highlight a large stability range (up to 1.4 Mbar) of the low-pressure phase. The compressibility behaviour was characterized by an accurate determination of the pressure-volume equation of state, with a bulk modulus of 339(3) GPa and its derivative of 5.3(1). X-ray absorption spectroscopy, which probes the local structure and the empty density of electronic states above the Fermi level, was also utilized. The remarkable agreement observed between experimental and calculated spectra validates the reliability of theoretical predictions of the pressure dependence of the electronic structure of iridium in the studied interval of compressions.
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| 40. |
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| 41. |
- Oosten, Astrid W, et al.
(författare)
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A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients.
- 2017
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 56:7, s. 733-746
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral and subcutaneous morphine is widely used for the treatment of cancer-related pain; however, solid pharmacokinetic data on this practice are lacking. Furthermore, it is largely unknown which factors contribute to the variability in clearances of morphine and its metabolites and whether morphine clearance is related to treatment outcome.METHODS: Blood samples from 49 cancer patients treated with oral and/or subcutaneous morphine were prospectively collected and were used to develop a population pharmacokinetic model for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The influence of age, gender, renal function and several polymorphisms possibly related to the pharmacokinetics of the three compounds was investigated. In addition, the relation between treatment failure and morphine and metabolite clearances was explored.RESULTS: A one-compartment model including an extensive first-pass effect adequately described the data of morphine and its metabolites. Estimated mean area under the plasma concentration-time curve (AUC) ratios following oral versus subcutaneous administration were: M3G/morphine 29.7:1 vs. 11.1:1; M6G/morphine 5.26:1 vs. 1.95:1; and M3G/M6G 5.65:1 vs. 5.70:1. Renal function was significantly correlated with clearance of the metabolites, which increased 0.602 L/h per every 10 mL/min/1.73 m(2) increase of estimated glomerular filtration rate (eGFR), reaching a plateau for eGFR >90 mL/min/1.73 m(2). The clearance of morphine or its metabolites was not found to be correlated with treatment failure.CONCLUSION: The influence of age-, gender- and pharmacokinetic-related polymorphisms was not identified on the pharmacokinetics of morphine. Clearance of morphine or its metabolites was not found to explain treatment outcome; however, large variations in plasma concentrations of morphine, M3G and M6G support further studies on the relation between plasma concentrations and treatment outcome. Dutch Trial Register ID: NTR4369.
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| 42. |
- Oosten, Astrid W., et al.
(författare)
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Treatment with subcutaneous and transdermal fentanyl : results from a population pharmacokinetic study in cancer patients
- 2016
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 72:4, s. 459-467
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Tidskriftsartikel (refereegranskat)abstract
- Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.
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| 43. |
- Salmeron, C., et al.
(författare)
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Effects of nutritional status on plasma leptin levels and in vitro regulation of adipocyte leptin expression and secretion in rainbow trout
- 2015
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480. ; 210, s. 114-123
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Tidskriftsartikel (refereegranskat)abstract
- As leptin has a key role on appetite, knowledge about leptin regulation is important in order to understand the control of energy balance. We aimed to explore the modulatory effects of adiposity on plasma leptin levels in vivo and the role of potential regulators on leptin expression and secretion in rainbow trout adipocytes in vitro. Fish were fed a regular diet twice daily ad libitum or a high-energy diet once daily at two ration levels; satiation (SA group) or restricted (RE group) to 25% of satiation, for 8 weeks. RE fish had significantly reduced growth (p < 0.001) and adipose tissue weight (p < 0.001), and higher plasma leptin levels (p = 0.022) compared with SA fish. Moreover, plasma leptin levels negatively correlated with mesenteric fat index (p = 0.009). Adipocytes isolated from the different fish were treated with insulin, ghrelin, leucine, eicosapentaenoic acid or left untreated (control). In adipocytes from fish fed regular diet, insulin and ghrelin increased leptin secretion dose-dependently (p = 0.002; p = 0.033, respectively). Leptin secretion in control adipocytes was significantly higher in RE than in SA fish (p = 0.022) in agreement with the in vivo findings, indicating that adipose tissue may contribute to the circulating leptin levels. No treatment effects were observed in adipocytes from the high-energy diet groups, neither in leptin expression nor secretion, except that leptin secretion was significantly reduced by leucine in RE fish adipocytes (p = 0.025). Overall, these data show that the regulation of leptin in rainbow trout adipocytes by hormones and nutrients seems to be on secretion, rather than at the transcriptional level. (C) 2014 Elsevier Inc. All rights reserved.
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| 44. |
- Salmeron, C., et al.
(författare)
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Roles of leptin and ghrelin in adipogenesis and lipid metabolism of rainbow trout adipocytes in vitro
- 2015
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Ingår i: Comparative Biochemistry and Physiology a-Molecular & Integrative Physiology. - : Elsevier BV. - 1095-6433. ; 188, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- Leptin and ghrelin are important regulators of energy homeostasis in mammals, whereas their physiological-roles in fish have not been fully elucidated. In the present study, the effects of leptin and ghrelin on adipogenesis, lipolysis and on expression of lipid metabolism-related genes were examined in rainbow trout adipocytes in vitro. Leptin expression and release increased from preadipocytes to mature adipocytes in culture, but did not affect the process of adipogenesis. While ghrelin and its receptor were identified in cultured differentiated adipocytes, ghrelin did not influence either preadipocyte proliferation or differentiation, indicating that it may have other adipose-related roles. Leptin and ghrelin increased lipolysis in mature freshly isolated adipocytes, but mRNA expression of lipolysis markers was not significantly modified. Leptin significantly suppressed the fatty acid transporter-1 expression, suggesting a decrease in fatty acid uptake and storage, but did not affect expression of any of the lipogenesis or beta-oxidation genes studied. Ghrelin significantly increased the mRNA levels of lipoprotein lipase, fatty acid synthase and peroxisome proliferator-activated receptor-beta, and thus appears to stimulate synthesis of triglycerides as well as their mobilization. Overall, the study indicates that ghrelin, but not leptin seems to be an enhancer of lipid turn-over in adipose tissue of rainbow trout, and this regulation may at least partly be mediated through autocrine/paracrine mechanisms. The mode of action of both hormones needs to be further explored to better understand their roles in regulating adiposity in fish. (C) 2015 Elsevier Inc. All rights reserved.
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| 45. |
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| 46. |
- Villarino, Ernesto, et al.
(författare)
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Large-scale ocean connectivity and planktonic body size
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Global patterns of planktonic diversity are mainly determined by the dispersal of propagules with ocean currents. However, the role that abundance and body size play in determining spatial patterns of diversity remains unclear. Here we analyse spatial community structure - beta-diversity - for several planktonic and nektonic organisms from prokaryotes to small mesopelagic fishes collected during the Malaspina 2010 Expedition. beta-diversity was compared to surface ocean transit times derived from a global circulation model, revealing a significant negative relationship that is stronger than environmental differences. Estimated dispersal scales for different groups show a negative correlation with body size, where less abundant large-bodied communities have significantly shorter dispersal scales and larger species spatial turnover rates than more abundant small-bodied plankton. Our results confirm that the dispersal scale of planktonic and micro-nektonic organisms is determined by local abundance, which scales with body size, ultimately setting global spatial patterns of diversity.
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