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| 2. |
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| 3. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 7. |
- Abdalla, H., et al.
(författare)
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HESS J1741-302 : a hidden accelerator in the Galactic plane
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- The H.E.S.S. Collaboration has discovered a new very high energy (VHE, E > 0.1 TeV) gamma-ray source, HESS J1741-302, located in the Galactic plane. Despite several attempts to constrain its nature, no plausible counterpart has been found so far at X-ray and MeV/GeV gamma-ray energies, and the source remains unidentified. An analysis of 145-h of observations of HESS J1741-302 at VHEs has revealed a steady and relatively weak TeV source (similar to 1% of the Crab Nebula flux), with a spectral index of Gamma = 2.3 +/- 0.2(stat) +/- 0.2(sys), extending to energies up to 10 TeV without any clear signature of a cut-off. In a hadronic scenario, such a spectrum implies an object with particle acceleration up to energies of several hundred TeV. Contrary to most H.E.S.S. unidentified sources, the angular size of HESS J1741-302 is compatible with the H.E.S.S. point spread function at VHEs, with an extension constrained to be below 0.068 degrees at a 99% confidence level. The gamma-ray emission detected by H.E.S.S. can be explained both within a hadronic scenario, due to collisions of protons with energies of hundreds of TeV with dense molecular clouds, and in a leptonic scenario, as a relic pulsar wind nebula, possibly powered by the middle-aged (20 kyr) pulsar PSR B1737-30. A binary scenario, related to the compact radio source 1LC 358.266+0.038 found to be spatially coincident with the best fit position of HESS J1741-302, is also envisaged.
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| 8. |
- Ochi, Y, et al.
(författare)
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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2833-
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Tidskriftsartikel (refereegranskat)abstract
- Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.
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| 9. |
- Nakajima, K., et al.
(författare)
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Diagnostic accuracy of an artificial neural network compared with statistical quantitation of myocardial perfusion images: a Japanese multicenter study
- 2017
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 44:13, s. 2280-2289
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Artificial neural networks (ANN) might help to diagnose coronary artery disease. This study aimed to determine whether the diagnostic accuracy of an ANN-based diagnostic system and conventional quantitation are comparable. Methods The ANN was trained to classify potentially abnormal areas as true or false based on the nuclear cardiology expert interpretation of 1001 gated stress/rest Tc-99m-MIBI images at 12 hospitals. The diagnostic accuracy of the ANN was compared with 364 expert interpretations that served as the gold standard of abnormality for the validation study. Conventional summed stress/rest/difference scores (SSS/SRS/SDS) were calculated and compared with receiver operating characteristics (ROC) analysis. Results The ANN generated a better area under the ROC curves (AUC) than SSS (0.92 vs. 0.82, p < 0.0001), indicating better identification of stress defects. The ANN also generated a better AUC than SDS (0.90 vs. 0.75, p < 0.0001) for stress-induced ischemia. The AUC for patients with old myocardial infarction based on rest defects was 0.97 (0.91 for SRS, p = 0.0061), and that for patients with and without a history of revascularization based on stress defects was 0.94 and 0.90 (p = 0.0055 and p < 0.0001 vs. SSS, respectively). The SSS/SRS/SDS steeply increased when ANN values (probability of abnormality) were > 0.80. Conclusion The ANN was diagnostically accurate in various clinical settings, including that of patients with previous myocardial infarction and coronary revascularization. The ANN could help to diagnose coronary artery disease.
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| 10. |
- Nakajima, K., et al.
(författare)
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Diagnostic Performance of Artificial Neural Network for Detecting Ischemia in Myocardial Perfusion Imaging
- 2015
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Ingår i: Circulation Journal. - 1346-9843. ; 79:7, s. 1549-1556
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI). Methods and Results: A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92 +/- 0.11 vs. 0.25 +/- 0.32, P<0.0001) and higher in the ischemia group than in the noischemia group (0.70 +/- 0.40 vs. 0.004 +/- 0.032, P<0.0001). Receiver-operating characteristics curve analysis showed comparable diagnostic accuracy between ANN and the scoring methods (0.971 vs. 0.980 for stress defect, and 0.882 vs. 0.937 for ischemia, both P=NS). The relationship between the ANN and defect scores was non-linear, with the ANN rapidly increased in ranges of summed stress score of 2-7 and summed defect score of 2-4. Conclusions: Although the diagnostic ability of ANN was similar to that of conventional scoring methods, the ANN could provide a different viewpoint for judging abnormality, and thus is a promising method for evaluating abnormality in MPI.
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| 11. |
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| 13. |
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| 14. |
- Nakajima, K., et al.
(författare)
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Artificial neural network retrained to detect myocardial ischemia using a Japanese multicenter database
- 2018
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Ingår i: Annals of Nuclear Medicine. - : Springer Science and Business Media LLC. - 0914-7187 .- 1864-6433. ; 32:5, s. 303-310
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Tidskriftsartikel (refereegranskat)abstract
- An artificial neural network (ANN) has been applied to detect myocardial perfusion defects and ischemia. The present study compares the diagnostic accuracy of a more recent ANN version (1.1) with the initial version 1.0. We examined 106 patients (age, 77 +/- 10 years) with coronary angiographic findings, comprising multi-vessel disease ( 50% stenosis) (52%) or old myocardial infarction (27%), or who had undergone coronary revascularization (30%). The ANN versions 1.0 and 1.1 were trained in Sweden (n = 1051) and Japan (n = 1001), respectively, using Tc-99m-methoxyisobutylisonitrile myocardial perfusion images. The ANN probabilities (from 0.0 to 1.0) of stress defects and ischemia were calculated in candidate regions of abnormalities. The diagnostic accuracy was compared using receiver-operating characteristics (ROC) analysis and the calculated area under the ROC curve (AUC) using expert interpretation as the gold standard. Although the AUC for stress defects was 0.95 and 0.93 (p = 0.27) for versions 1.1 and 1.0, respectively, that for detecting ischemia was significantly improved in version 1.1 (p = 0.0055): AUC 0.96 for version 1.1 (sensitivity 87%, specificity 96%) vs. 0.89 for version 1.0 (sensitivity 78%, specificity 97%). The improvement in the AUC shown by version 1.1 was also significant for patients with neither coronary revascularization nor old myocardial infarction (p = 0.0093): AUC = 0.98 for version 1.1 (sensitivity 88%, specificity 100%) and 0.88 for version 1.0 (sensitivity 76%, specificity 100%). Intermediate ANN probability between 0.1 and 0.7 was more often calculated by version 1.1 compared with version 1.0, which contributed to the improved diagnostic accuracy. The diagnostic accuracy of the new version was also improved in patients with either single-vessel disease or no stenosis (n = 47; AUC, 0.81 vs. 0.66 vs. p = 0.0060) when coronary stenosis was used as a gold standard. The diagnostic ability of the ANN version 1.1 was improved by retraining using the Japanese database, particularly for identifying ischemia.
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| 15. |
- Nakajima, K., et al.
(författare)
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Improved quantification of small hearts for gated myocardial perfusion imaging
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:8, s. 1163-1170
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Tidskriftsartikel (refereegranskat)abstract
- In patients with a small heart, defined as an end-systolic volume (ESV) of a parts per thousand currency sign20 mL calculated using the Quantitative Gated SPECT (QGS) program, underestimation of ESV and overestimation of ejection fraction (EF) using gated myocardial perfusion imaging are considered errors caused by inappropriate delineation of the left ventricle (LV). The aim of this study was to develop a new method for delineation of the LV and to evaluate it in studies using a digital phantom, normal subjects and patients. The active shape-based method for LV delineation, EXINI heart (ExH), was adjusted to more accurately process small hearts. In small hearts, due to the partial volume effect and the short distance to the opposite ventricular wall, the endocardial and the epicardial surfaces are shifted in the epicardial direction depending on the midventricular volume. The adjusted method was evaluated using digital XCAT phantoms with Monte Carlo simulation (8 virtual patients), a Japanese multicentre normal database (69 patients) and consecutive Japanese patients (116 patients). The LV volumes, EF and diastolic parameters derived from ExH and QGS were compared. The digital phantom studies showed a mean ESV of 87 % +/- 9 % of the true volume calculated using ExH and 22 % +/- 18 % calculated using QGS. In the normal database, QGS gave higher EFs in women than in men (71.4 +/- 6.0 % vs. 67.2 +/- 6.0 %, p = 0.0058), but ExH gave comparable EFs (70.7 +/- 4.9 % and 71.4 +/- 5 % in men and women, respectively, p = ns). QGS gave higher EFs in subjects with a small heart than in those with a normal-sized heart (74.5 +/- 5.1 % vs. 66.1 +/- 4.9 %), but ExH gave comparable values (70.0 +/- 5.9 % vs. 71.6 +/- 4.2 %, respectively, p = ns). In consecutive patients, the average EFs with QGS in patients with ESV > 20 mL, 11-20 mL and a parts per thousand currency sign10 mL were 57.9 %, 71.9 % and 83.2 %, but with ExH the differences among these groups were smaller (65.2 %, 67.8 % and 71.5 %, respectively). The volume-dependent edge correction algorithm was able to effectively reduce the effects on ESV and EF of a small heart. The uniform normal values might be applicable to both men and women and to both small and normal-sized hearts.
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| 19. |
- Usachov, D. Yu, et al.
(författare)
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Cubic Rashba Effect in the Surface Spin Structure of Rare-Earth Ternary Materials
- 2020
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Ingår i: Physical Review Letters. - 0031-9007. ; 124:23
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Tidskriftsartikel (refereegranskat)abstract
- Spin-orbit interaction and structure inversion asymmetry in combination with magnetic ordering is a promising route to novel materials with highly mobile spin-polarized carriers at the surface. Spin-resolved measurements of the photoemission current from the Si-terminated surface of the antiferromagnet TbRh2Si2 and their analysis within an ab initio one-step theory unveil an unusual triple winding of the electron spin along the fourfold-symmetric constant energy contours of the surface states. A two-band k·p model is presented that yields the triple winding as a cubic Rashba effect. The curious in-plane spin-momentum locking is remarkably robust and remains intact across a paramagnetic-antiferromagnetic transition in spite of spin-orbit interaction on Rh atoms being considerably weaker than the out-of-plane exchange field due to the Tb 4f moments.
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| 20. |
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| 21. |
- Rojas-Macias, Miguel A., 1979, et al.
(författare)
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Towards a standardized bioinformatics infrastructure for N- and O-glycomics
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N-and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.
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| 24. |
- Xu, Su-Yang, et al.
(författare)
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Lifshitz transition and Van Hove singularity in a three-dimensional topological Dirac semimetal
- 2015
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 92:7
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Tidskriftsartikel (refereegranskat)abstract
- A three-dimensional (3D) Dirac semimetal is a novel state of quantum matter which has recently attracted much attention as an apparent 3D version of graphene. In this paper, we report results on the electronic structure of the 3D Dirac semimetal Na3Bi at a surface that reveals its nontrivial ground state. Our studies reveal that the two 3D Dirac cones go through a topological change in the constant energy contour as a function of the binding energy, featuring a Lifshitz point, which is missing in a strict 3D analog of graphene. Our results identify an example of a band saddle-point singularity in 3D Dirac materials. This is in contrast to its two-dimensional analogs such as graphene and the Dirac surface states of a topological insulator. The observation of multiple Dirac nodes in Na3Bi connecting via a Lifshitz point along its crystalline rotational axis away from the Kramers point serves as a decisive signature for the symmetry-protected nature of the Dirac semimetal's topological bulk ground state.
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| 25. |
- Yamada, K., et al.
(författare)
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Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis
- 2021
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 30, s. 2020-2032
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. Methods Patients with de novo DLS, aged >= 65 years, who had LBP with visual analog scale (VAS) of >= 50 for >= 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. Results One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 +/- 32.4 and 43.9 +/- 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. Conclusion Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.
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| 26. |
- Yoneyama, H., et al.
(författare)
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Reducing the small-heart effect in pediatric gated myocardial perfusion single-photon emission computed tomography
- 2017
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 24:4, s. 1378-1388
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Tidskriftsartikel (refereegranskat)abstract
- Background. We compared two reconstruction algorisms and two cardiac functional evaluation software programs in terms of their accuracy for estimating ejection fraction (EF) of small hearts (SH). Methods. The study group consisted of 66 pediatric patients. Data were reconstructed using a filtered back projection (FBP) method without the resolution correction (RC) and an iterative method based on an ordered subset expectation maximization (OSEM) algorithm with the RC. EF was evaluated using two software programs of quantitative gated single-photon emission computed tomography (SPECT) (QGS) and cardioREPO. We compared the EF of gated myocardial perfusion SPECT to echocardiographic measurement (Echo). Results. Forty-eight of 66 patients had an end-systolic volume < 20 mL which was used as the criterion for being included in the SH group, and the SH effect led to an overestimation of EF. While significant differences were observed between Echo (66.9 +/- 5.0%) and QGS-FBP without RC (76.9 +/- 8.4%, P < .0001), QGS-OSEM with RC (76.6 +/- 8.6%, P < .0001), and cardioREPO-FBP without RC (72.1 +/- 10.0%, P = .0011), no significant difference was observed between Echo and cardioREPO-OSEM with RC (67.4 +/- 6.1%) in SH group. Conclusions. In pediatric gated myocardial perfusion SPECT, the SH effect can be significantly reduced when an OSEM algorithm is used with RC in combination with the specific cardioREPO algorithm.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Baek, Sungmin, et al.
(författare)
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The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage
- 2019
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Ingår i: Developmental Cell. - : CELL PRESS. - 1534-5807 .- 1878-1551. ; 49:2, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.
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| 31. |
- Chaudhury, Smrita, et al.
(författare)
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Localised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo
- 2020
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Ingår i: Development. - : COMPANY BIOLOGISTS LTD. - 0950-1991 .- 1477-9129. ; 147:18
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Tidskriftsartikel (refereegranskat)abstract
- The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprouts from cardinal veins followed by migration and proliferation to colonise embryonic tissues. Although much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified mbtps1 and sec23a, components of the COP-II protein secretory pathway, as essential for developmental lymphangiogenesis. In both mutants, LECs initially depart the cardinal vein but then fail in their ongoing migration. A key cargo that failed to be secreted in both mutants was a type II collagen (Col2a1). Col2a1 is normally secreted by notochord sheath cells, alongside which LECs migrate. col2a1a mutants displayed defects in the migratory behaviour of LECs and failed lymphangiogenesis. These studies thus identify Col2a1 as a key cargo secreted by notochord sheath cells and required for the migration of LECs. These findings combine with our current understanding to suggest that successive cell-to-cell and cell-matrix interactions regulate the migration of LECs through the embryonic environment during development.
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| 32. |
- Grenz, Pascal Jona, et al.
(författare)
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Adlayer influence on Dirac-type surface state at W(110)
- 2021
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Ingår i: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 33:28
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Tidskriftsartikel (refereegranskat)abstract
- In a combined experimental and theoretical study, we investigated how Fe and Co adlayers on W(110) affect the Dirac-type surface state (DSS). Angle-resolved photoelectron spectroscopy data show an increase in binding energy of 75meV and 107meV for Fe and Co, respectively. In order to identify the origin of the energy shift we performed first-principles calculations of the surface electronic structure. The inward surface relaxation of the uncovered W(110) surface is lifted by the adlayers. This structural change is one reason of the energy shift of the DSS. Furthermore, the Fe and Co adlayers change the surface potential, which results in an additional energy shift of the DSS.
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| 33. |
- Grimm, Lin, et al.
(författare)
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Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development
- 2023
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Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 42:11
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Tidskriftsartikel (refereegranskat)abstract
- During development, the lymphatic vasculature forms as a second, new vascular network derived from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is the first step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet downstream mechanisms remain to be elucidated. We present a single cell transcriptomic atlas of lymphangiogenesis in zebrafish revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a VEC-LEC fate reversion during differentiation. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new transcriptional targets and regulatory regions of the genome downstream of Prox1 in LEC maintenance, as well as showing that Prox1 specifies LEC fate primarily by limiting blood vascular and hematopoietic fate. This extensive single cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development.
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| 34. |
- Hinkula, J, et al.
(författare)
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Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuLV pseudovirus challenge in vivo
- 2004
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Ingår i: Cells, tissues, organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 177:3, s. 169-184
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Tidskriftsartikel (refereegranskat)abstract
- Superinfection by HIV-1 of a cell line containing the complete murine leukemia virus (MuLV) genome was shown to give rise to pseudotyped HIV-1/MuLV. Such superinfection was successful with certain strains of HIV-1 subtypes A–D. Primary spleen cells and cells of the peritoneal cavity of immunocompetent mice of the C57Bl/6 strain were infectable with the pseudotype HIV-1/MuLV and secreted HIV-1 in vitro and in vivo. In contrast, the murine cell lines, NIH 3T3, myeloma cell line Sp2/0, and two murine hybridoma cell lines were relatively resistant to infection and produced no or little HIV. After primary murine spleen cells had been infected with pseudotyped HIV-1 and transferred to C57Bl/6 mice, replication-competent HIV-1 was obtained from the peritoneal cavity for at least 10–14 days. High amounts (>10<sup>5</sup> vRNA copies/ml) of HIV-1 vRNA could be measured in the peritoneal fluid. Presence of HIV-1 proviral DNA was detectable in cells from the peritoneal cavity for up to 24 days after infected cell transfer. Active reverse transcriptase representing both HIV-1 and C-type murine retroviruses was detected in the peritoneal washes. The HIV-infected spleen cells injected into the peritoneal cavity elicited HIV-1-specific cellular immune responses to p24gag, gp160Env, Nef, Tat and Rev. Mice immunized with HIV-1 DNA, but not with HIV-1 protein, cleared their HIV-1-infected cells within 10–14 days after challenge with HIV-1/MuLV-infected syngeneic spleen cells. This novel model system of primarily cellular reactivity to HIV-1-infected cells in vivo may become useful for assaying experimental HIV-1 immunization schedules.
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| 35. |
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| 36. |
- Koltowska, Katarzyna, et al.
(författare)
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The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function
- 2021
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Ingår i: Nature Cell Biology. - : Springer Nature. - 1465-7392 .- 1476-4679. ; 23:11, s. 1136-1147
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Tidskriftsartikel (refereegranskat)abstract
- Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells. The development of a functional vasculature requires the coordinated control of cell fate, lineage differentiation and network growth. Cellular proliferation is spatiotemporally regulated in developing vessels, but how this is orchestrated in different lineages is unknown. Here, using a zebrafish genetic screen for lymphatic-deficient mutants, we uncover a mutant for the RNA helicase Ddx21. Ddx21 cell-autonomously regulates lymphatic vessel development. An established regulator of ribosomal RNA synthesis and ribosome biogenesis, Ddx21 is enriched in sprouting venous endothelial cells in response to Vegfc-Flt4 signalling. Ddx21 function is essential for Vegfc-Flt4-driven endothelial cell proliferation. In the absence of Ddx21, endothelial cells show reduced ribosome biogenesis, p53 and p21 upregulation and cell cycle arrest that blocks lymphangiogenesis. Thus, Ddx21 coordinates the lymphatic endothelial cell response to Vegfc-Flt4 signalling by balancing ribosome biogenesis and p53 function. This mechanism may be targetable in diseases of excessive lymphangiogenesis such as cancer metastasis or lymphatic malformation.
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| 40. |
- Qi, QB, et al.
(författare)
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Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 64:7, s. 2467-2476
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Tidskriftsartikel (refereegranskat)abstract
- The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.
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| 41. |
- Wortelen, H., et al.
(författare)
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Spin-orbit influence on dz2 -type surface state at Ta(110)
- 2015
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 92:16
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Tidskriftsartikel (refereegranskat)abstract
- The influence of spin-orbit interaction on an occupied surface state at Ta(110) is investigated with spin- and angle-resolved photoemission and electronic structure calculations. The surface state appears in a symmetry gap at a binding energy of 0.45 eV at Γ¯ and exhibits a free-electron-like E(k) dispersion with an effective mass m∗/me of about -1.35 along Γ¯H¯. Photoemission results for excitation with s- and p-polarized light confirm the predicted dz2-type symmetry of the state close to Γ¯. Spin-resolved data for finite k reveal a pure Rashba-type spin texture with a Rashba parameter of 0.063±0.007eVÅ. These findings clearly prove a sizable impact of spin-orbit coupling on the dz2 surface state and resolve a longstanding disagreement on this issue.
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| 42. |
- Yamada, K., et al.
(författare)
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Targeted Therapy for Low Back Pain in Elderly Degenerative Lumbar Scoliosis
- 2016
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Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436. ; 41:10, s. 872-879
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Prospective cohort study. Objective. To compare the novel treatment procedure with nonoperative treatment for low back pain (LBP) in elderly patients with degenerative lumbar scoliosis (DLS). Summary of Background Data. Treatment of LBP associated with elderly DLS is controversial. We developed a novel treatment procedure, termed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI). Methods. We included patients with de novo DLS aged >= 65 years who had LBP with a visual analogue scale (VAS) score of >50 for >= 6 months with intervertebral vacuum and vertebral bone marrow edema (BME) defined on fat-saturated T2-weighted or gadolinium-enhanced T1-weighted magnetic resonance imaging. The primary outcomes were evaluated using the VAS score and modified Oswestry Disability Index (ODI). As an objective measurement, we scored BME on magnetic resonance imaging. Results. Between August 2004 and July 2011, 109 patients underwent PIPI and 53 received nonoperative treatment. At 1 month, mean improvements in VAS scores were -55.3 (95% CI, -60.5 to -50.1) and -1.9 (CI, -7.7 to 3.8) and mean improvements in ODI were -22.7 (CI, -27.3 to -18.2) and -0.6 (CI, -6.6 to 5.4) for the PIPI and nonoperative groups, respectively. At 2 years, mean improvements in VAS scores were -52.2 (CI, -59.9 to -44.4) and -4.0 (CI, -10.9 to 3.0) and mean improvements in ODI were -20.7 (CI, -27.3 to -14.5) and -1.0 (CI, -7.7 to 5.7) for the PIPI and nonoperative groups, respectively. BME substantially decreased in the PIPI group compared with the nonoperative group (P < 0.001) and correlated with VAS score and ODI improvements (VAS score: r = 0.502, P < 0.001; ODI: r = 0.372, P< 0.001). Conclusion. PIPI improved treatment for LBP, with a sustained clinical benefit for at least 2 years.
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| 43. |
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