| 1. |
- Dispenzieri, Angela, et al.
(författare)
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Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) : 14-year update
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs.Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021).Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation.Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease.ClinicalTrials.gov Identifier: NCT00628745.
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| 2. |
- Ekoff, Maria, et al.
(författare)
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The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:9, s. 3209-3217
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue-like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53-/- mast cells, we found that cytokine deprivation-induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wildtype cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation-induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo. © 2007 by The American Society of Hematology.
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| 3. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Tidskriftsartikel (refereegranskat)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 4. |
- Edwards, Marten O. M., et al.
(författare)
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Increased photoelectron transmission in High-pressure photoelectron spectrometers using "swift acceleration"
- 2015
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 785, s. 191-196
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Tidskriftsartikel (refereegranskat)abstract
- A new operation mode of a HPXPS (high-pressure X-ray photoelectron spectroscopy) analyzer is evaluated on a HPXPS system fitted with an Al K alpha X-ray source. A variety of metal foil samples (gold, silver and copper) were measured in different sample gas environments (N-2 and H2O), and a front aperture diameter of 0.8 mm. The new design concept is based upon "swiftly" accelerating the photoelectrons to kinetic energies of several keV after they pass the analyzer front aperture. Compared to the standard mode, in which the front section between the two first apertures is field-free, this gives a wider angular collection and a lower tendency for electron losses in collisions with gas molecules within the analyzer. With the swift-acceleration mode we attain, depending on the experimental conditions, up to about 3 times higher peak intensities in vacuum and about 10 to 20 times higher peak intensities in the 6-9 mbar regime, depending on kinetic energy. These experimental findings agree well with simulated transmission functions for the analyzer. The new mode of operation enables faster data acquisition than the standard mode of operation, particularly valuable in a home laboratory environment. Further demonstrations of performance are highlighted by measurements of the valence band structure in dye sensitized solar cell photoelectrodes under a 2 mbar H2O atmosphere, a molecularly modified surface of interest in photoelectrochemical devices.
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| 7. |
- Hågvar, Sigmund, et al.
(författare)
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Ecosystem birth near melting glaciers : A review on the pioneer role of ground-dwelling arthropods
- 2020
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Ingår i: Insects. - : MDPI AG. - 2075-4450. ; 11:9, s. 1-35
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Forskningsöversikt (refereegranskat)abstract
- As glaciers retreat, their forelands represent “natural laboratories” for the study of primary succession. This review describes how certain arthropods conquer pristine ground and develop food webs before the establishment of vascular plants. Based on soil samples, pitfall traps, fallout and sticky traps, gut content studies, and some unpublished data, we compare early arthropod succession on glacial forelands of northern Europe (Iceland, Norway including Svalbard, and Sweden) and of the Alps (Austria, Italy). While macroarthropod predators like ground beetles (Coleoptera: Carabidae), harvestmen (Arachnida: Opiliones), and spiders (Arachnida: Araneae) have usually been considered as pioneers, assumed to feed on airborne prey, this review explains a different pattern. Here, we highlight that springtails (Collembola), probably feeding on biofilm made up of algae or cyanobacteria, are super-pioneers, even at high altitudes and under arctic conditions. We also point out that macroarthropod predators can use locally available prey, such as springtails or non-biting midges (Diptera: Chironomidae). Pioneer arthropod communities vary under different biogeographical and climatic conditions. Two pioneer food webs, from northern Europe and the Alps, respectively, differed in structure and function. However, certain genera and orders were common to both. Generalists and specialists live together in a pioneer community. Cold-adapted specialists are threatened by glacier melting.
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| 8. |
- Kaufmann, Odd Tore, et al.
(författare)
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Teachers’ Error-handling Practices Within and Across Lesson Phases in the Mathematics Classroom
- 2022
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Ingår i: International Journal of Science and Mathematics Education. - : Springer. - 1571-0068 .- 1573-1774.
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Tidskriftsartikel (refereegranskat)abstract
- Multiple studies have been conducted regarding teachers’ error-handling practices, and how errors can be treated as opportunities for learning, albeit in the context of whole-class discussions. The aim of the present research is to continue to investigate teachers’ error-handling practices as they occur in different phases of maths lessons: introduction of the task, when students are working alone, and when students are working in pairs and finally, as part of the whole-class discussion. The study included 51 lessons from twelve teachers. A cross-case analysis was made across the individual teacher cases to look for similarities and differences between different teachers’ error-handling practices across the lesson phases in order to create teaching profiles with similar handling of student errors across the lesson phases. Five error-handling teaching profiles were identified; correcting errors throughout all phases, correcting errors during students’ work while few errors are brought up in whole class, correcting errors during students’ work while using a variety of practices in whole class, ignoring errors while using some of them in whole class, and discussing and explaining errors.
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| 10. |
- Oji, Satoru, et al.
(författare)
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Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord
- 2016
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:3, s. e0151244-
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Tidskriftsartikel (refereegranskat)abstract
- Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen-specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN.
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