| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 6. |
- Bakker, M. K., et al.
(författare)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 7. |
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| 8. |
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| 9. |
- MacDougall, Andrew S., et al.
(författare)
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Widening global variability in grassland biomass since the 1980s
- 2024
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Global change is associated with variable shifts in the annual production of aboveground plant biomass, suggesting localized sensitivities with unclear causal origins. Combining remotely sensed normalized difference vegetation index data since the 1980s with contemporary field data from 84 grasslands on 6 continents, we show a widening divergence in site-level biomass ranging from +51% to −34% globally. Biomass generally increased in warmer, wetter and species-rich sites with longer growing seasons and declined in species-poor arid areas. Phenological changes were widespread, revealing substantive transitions in grassland seasonal cycling. Grazing, nitrogen deposition and plant invasion were prevalent in some regions but did not predict overall trends. Grasslands are undergoing sizable changes in production, with implications for food security, biodiversity and carbon storage especially in arid regions where declines are accelerating.
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| 10. |
- Adams, D, et al.
(författare)
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Measurement of the SMC muon beam polarisation using the asymmetry in the elastic scattering off polarised electrons
- 2000
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 443:1, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- A muon beam polarimeter was built for the SMC experiment at the CERN SPS, for beam energies of 100 and 190 GeV. The beam polarisation is determined from the asymmetry in the elastic scattering off the polarised electrons of a ferromagnetic target whose ma
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| 11. |
- Ambainis, A., et al.
(författare)
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Quantum finite multitape automata
- 1999
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Ingår i: SOFSEM’99: Theory and Practice of Informatics. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783540666943 ; , s. 340-348
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Konferensbidrag (refereegranskat)abstract
- Quantum finite automata were introduced by C. Moore, J. P. Crutchfield [4], and by A. Kondacs and J. Watrous [3]. This notion is not a generalization of the deterministic finite automata. Moreover, in [3] it was proved that not all regular languages can be recognized by quantum finite automata. A. Ambainis and R. Freivalds [1] proved Chat for some languages quantum finite automats may be exponentially more concise rather than both deterministic and probabilistic finite automata. In this paper we introduce the notion of quantum finite multi-tape automata and prove that there is a language recognized by a quantum finite automaton but not by deterministic or probabilistic finite automats. This is the first result on a problem which can be solved by a quantum computer but not by a deterministic or probabilistic computer. Additionally we discover unexpected probabilistic automata recognizing complicated languages.
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| 12. |
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| 13. |
- Fiedler, Heidelore, 1953-, et al.
(författare)
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PCDD, PCDF, and PCB in farm-raised catfish from southeast United States - Concentrations, sources, and CYP1A induction
- 1998
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 37:9-12, s. 1645-1656
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Tidskriftsartikel (refereegranskat)abstract
- Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and-PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.
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| 14. |
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| 15. |
- Norin, U., et al.
(författare)
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Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the CTLA-4 recombinant fusion protein has demonstrated therapeutic effects by selectively modulating T-cell activation in rheumatoid arthritis. Here we show, using a forward genetic approach, that a mutation in the SH3gl1 gene encoding the endocytic protein Endophilin A2 is associated with the development of arthritis in rodents. Defective expression of SH3gl1 affects T cell effector functions and alters the activation threshold of autoreactive T cells, thereby leading to complete protection from chronic autoimmune inflammatory disease in both mice and rats. We further show that SH3GL1 regulates human T cell signaling and T cell receptor internalization, and its expression is upregulated in rheumatoid arthritis patients. Collectively our data identify SH3GL1 as a key regulator of T cell activation, and as a potential target for treatment of autoimmune diseases. The autoimmune disorder, rheumatoid arthritis (RA), has been associated with multiple pathophysiological factors. Here the authors show that deficiency in endophilin A2 in rodents protects them from experimental arthritis by altering T cell activation threshold and effector functions, thereby hinting a potential target for RA therapy.
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| 16. |
- Tennis, M, et al.
(författare)
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p53 Mutation analysis in breast tumors by a DNA microarray method
- 2006
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 15:1, s. 80-85
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Tidskriftsartikel (refereegranskat)
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| 17. |
- Adams, D, et al.
(författare)
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A large Streamer Chamber muon tracking detector in a high-flux fixed-target application
- 1999
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 435:3, s. 354-374
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Arrays of limited streamer tubes of the Iarocci type were deployed in our experiment at CERN as part of a forward muon detector system with provisions for the beam to pass through the center of each panel in the array. A total of 16 4 m x 4 m panels were
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| 18. |
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| 19. |
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| 20. |
- Adams, D, et al.
(författare)
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The polarized double cell target of the SMC
- 1999
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 437:1, s. 23-67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The polarized target of the Spin Muon Collaboration at CERN was used for deep inelastic muon scattering experiments during 1993-1996 with a polarized muon beam to investigate the spin structure of the nucleon. Most of the experiments were carried out with
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| 21. |
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| 22. |
- Adeva, B, et al.
(författare)
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Large enhancement of deuteron polarization with frequency modulated microwaves
- 1996
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Ingår i: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. - 0168-9002. ; 372:3, s. 339-343
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liter polarized target using the method of dynamic nuclear polarization. This target was used during a deep
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| 23. |
- Akerman, Ildem, et al.
(författare)
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Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 25:2, s. 400-411
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
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| 24. |
- Aoun, M, et al.
(författare)
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Glycan Activation of Clec4b Induces Reactive Oxygen Species Protecting against Neutrophilia and Arthritis
- 2022
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Ingår i: Antioxidants (Basel, Switzerland). - : MDPI AG. - 2076-3921. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 and Clec4b to be major regulators of arthritis models in rats. Here, we investigate epistasis between Ncf1 and Clec4b, two major regulators of arthritis in rats. We find that Clec4b and Ncf1 exert an additive effect on arthritis given by their joint ability to regulate neutrophils. Both genes are highly expressed in neutrophils, together regulating neutrophil availability and their capacity to generate reactive oxygen species. Using a glycan array, we identify key ligands of Clec4b and demonstrate that Clec4b-specific stimulation triggers neutrophils into oxidative burst. Our observations highlight Clec4b as an important regulator of neutrophils and demonstrate how epistatic interactions affect the susceptibility to, and severity of, autoimmune arthritis.
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| 25. |
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