| 41. |
- De Zotti, G., et al.
(författare)
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Exploring cosmic origins with CORE : Extragalactic sources in cosmic microwave background maps
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We discuss the potential of a next generation space-borne Cosmic Microwave Background (CMB) experiment for studies of extragalactic sources. Our analysis has particular bearing on the definition of the future space project, CORE, that has been submitted in response to ESA's call for a Medium-size mission opportunity as the successor of the Planck satellite. Even though the effective telescope size will be somewhat smaller than that of Planck, CORE will have a considerably better angular resolution at its highest frequencies, since, in contrast with Planck, it will be diffraction limited at all frequencies. The improved resolution implies a considerable decrease of the source confusion, i.e. substantially fainter detection limits. In particular, CORE will detect thousands of strongly lensed high-z galaxies distributed over the full sky. The extreme brightness of these galaxies will make it possible to study them, via follow-up observations, in extraordinary detail. Also, the CORE resolution matches the typical sizes of high-z galaxy proto-clusters much better than the Planck resolution, resulting in a much higher detection efficiency; these objects will be caught in an evolutionary phase beyond the reach of surveys in other wavebands. Furthermore, CORE will provide unique information on the evolution of the star formation in virialized groups and clusters of galaxies up to the highest possible redshifts. Finally, thanks to its very high sensitivity, CORE will detect the polarized emission of thousands of radio sources and, for the first time, of dusty galaxies, at mm and sub-mm wavelengths, respectively.
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| 42. |
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| 43. |
- Chelban, V., et al.
(författare)
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PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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| 44. |
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| 45. |
- Beck, S., et al.
(författare)
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Experimenting with Open Innovation in Science (OIS) practices: A novel approach to co-developing research proposals
- 2021
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Ingår i: CERN IdeaSquare Journal of Experimental Innovation. - 2413-9505. ; 5:2, s. 28-49
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Tidskriftsartikel (refereegranskat)abstract
- Co-producing scientific research with those who are affected by it is an emerging phenomenon in contemporary science. This article summarizes and reflects on both the process and outcome of a novel experiment to co-develop scientific research proposals in the field of Open Innovation in Science (OIS), wherein scholars engaged in the study of open and collaborative practices collaborated with the “users” of their research, i.e., scientists who apply such practices in their own research. The resulting co-developed research proposals focus on scientific collaboration, open data, and knowledge sharing and are available as an appendix to this article.
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| 46. |
- Pagnamenta, A. T., et al.
(författare)
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An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144, s. 584-600
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Tidskriftsartikel (refereegranskat)abstract
- The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose 47000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 +/- 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.
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| 47. |
- Abeysekara, A. U., et al.
(författare)
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A Luminous and Isolated Gamma-Ray Flare from the Blazar B2 1215+30
- 2017
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 836:2
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Tidskriftsartikel (refereegranskat)abstract
- B2 1215+30 is a BL-Lac-type blazar that was first detected at TeV energies by the MAGIC atmospheric Cherenkov telescopes and subsequently confirmed by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory with data collected between 2009 and 2012. In 2014 February 08, VERITAS detected a large-amplitude flare from B2. 1215+30 during routine monitoring observations of the blazar 1ES. 1218+304, located in the same field of view. The TeV flux reached 2.4 times the Crab Nebula flux with a variability timescale of <3.6 hr. Multiwavelength observations with Fermi-LAT, Swift, and the Tuorla Observatory revealed a correlated high GeV flux state and no significant optical counterpart to the flare, with a spectral energy distribution where the gamma-ray luminosity exceeds the synchrotron luminosity. When interpreted in the framework of a onezone leptonic model, the observed emission implies a high degree of beaming, with Doppler factor delta > 10, and an electron population with spectral index p < 2.3.
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| 48. |
- Aliu, E., et al.
(författare)
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Investigating the TeV Morphology of MGRO J1908+06 with VERITAS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on deep observations of the extended TeV gamma-ray source MGRO J1908+06 made with the VERITAS very high energy gamma-ray observatory. Previously, the TeV emission has been attributed to the pulsar wind nebula (PWN) of theFermi-LAT pulsar PSR J1907+0602. We detect MGRO J1908+06 at a significance level of 14 standard deviations (14σ) and measure a photon index of 2.20 ± 0.10stat ± 0.20sys. The TeV emission is extended, covering the region near PSR J1907+0602 and also extending toward SNR G40.5-0.5. When fitted with a two-dimensional Gaussian, the intrinsic extension has a standard deviation of σsrc = 044 ± 002. In contrast to other TeV PWNe of similar age in which the TeV spectrum softens with distance from the pulsar, the TeV spectrum measured near the pulsar location is consistent with that measured at a position near the rim of G40.5-0.5, 033 away.
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| 49. |
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| 50. |
- Beck, S., et al.
(författare)
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The Open Innovation in Science research field: a collaborative conceptualisation approach
- 2022
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Ingår i: Industry and Innovation. - : Informa UK Limited. - 1366-2716 .- 1469-8390. ; 29:2, s. 136-185
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Tidskriftsartikel (refereegranskat)abstract
- Openness and collaboration in scientific research are attracting increasing attention from scholars and practitioners alike. However, a common understanding of these phenomena is hindered by disciplinary boundaries and disconnected research streams. We link dispersed knowledge on Open Innovation, Open Science, and related concepts such as Responsible Research and Innovation by proposing a unifying Open Innovation in Science (OIS) Research Framework. This framework captures the antecedents, contingencies, and consequences of open and collaborative practices along the entire process of generating and disseminating scientific insights and translating them into innovation. Moreover, it elucidates individual-, team-, organisation-, field-, and society-level factors shaping OIS practices. To conceptualise the framework, we employed a collaborative approach involving 47 scholars from multiple disciplines, highlighting both tensions and commonalities between existing approaches. The OIS Research Framework thus serves as a basis for future research, informs policy discussions, and provides guidance to scientists and practitioners.
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