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- Sellgren, C. M., et al.
(författare)
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GRK3 deficiency elicits brain immune activation and psychosis
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 6820-6832
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Tidskriftsartikel (refereegranskat)abstract
- The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3(-/-) mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1 beta, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3(-/-) mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.
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- Blomquist, Axel, et al.
(författare)
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Persistent Aspergillus fumigatus infection in cystic fibrosis : impact on lung function and role of treatment of asymptomatic colonization-a registry-based case-control study
- 2022
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Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization.METHODS: Data from 2014-2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects.RESULTS: A total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6-5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (- 8.7 vs - 1.4 percentage points, p < 0.05).CONCLUSION: Inhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.
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- Carlsson, Christina, et al.
(författare)
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Patientföreningarna som företrädare och röst
- 2006
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Ingår i: Det civila samhället som forskningsfält. Nya avhandlingar i ett nytt sekel. - 9178447283 - 9789178447282 ; , s. 38-49
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Chylicki, K, et al.
(författare)
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p53-mediated differentiation of the erythroleukemia cell line K562
- 2000
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Ingår i: Cell Growth and Differentiation. - 1044-9523. ; 11:6, s. 24-315
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Tidskriftsartikel (refereegranskat)abstract
- The tumor suppressor gene p53 can mediate both apoptosis and cell cycle arrest. In addition, p53 also influences differentiation. To further characterize the differentiation inducing properties of p53, we overexpressed a temperature-inducible p53 mutant (ptsp53Val135) in the erythroleukemia cell line K562. The results show that wild-type p53 and hemin synergistically induce erythroid differentiation of K562 cells, indicating that p53 plays a role in the molecular regulation of differentiation. However, wild-type p53 did not affect phorbol 12-myristate 13-acetate-dependent appearance of the megakaryocyte-related cell surface antigens CD9 and CD61, suggesting that p53 does not generally affect phenotypic modulation. The cyclin-dependent kinase inhibitor p21, a transcriptional target of p53, halts the cell cycle in G1 and has also been implicated in the regulation of differentiation and apoptosis. However, transiently overexpressed p21 did neither induce differentiation nor affect the cell cycle distribution or viability of K562 cells, suggesting that targets downstream of p53 other than p21 are critical for the p53-mediated differentiation response.
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- Domeij, Martin, et al.
(författare)
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2.2 kV SiC BJTs with low V(CESAT) fast switching and short-circuit capability
- 2010
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2009, PTS 1 AND 2. ; , s. 1033-1036
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Konferensbidrag (refereegranskat)abstract
- This paper reports large active area (15 mm(2)) 4H-SiC BJTS with a low V(CESAT)=0.6 V at 1(C)=20 A (J(C)=133 A/cm(2)) and an open-base breakdown voltage BV(CEO)=2.3 kV at T=25 degrees C. The corresponding room temperature specific on-resistance R(SP.ON)=4.5 m Omega cm(2) is to the authors knowledge the lowest reported value for a large area SiC BJT blocking more than 2 kV. The onstate and blocking characteristics were analyzed by device simulation and found to be in good agreement with measurements. Fast switching with VcE rise- and fall-times in the range of 20-30 ns was demonstrated for a 6 A 1200 V rated SiC BJT. It was concluded that high dynamic base currents are essential for fast switching to charge the BJT parasitic base-collector capacitance. In addition, 10 mu s short-circuit capability with V(CE)=800 V was shown for the 1200 V BJT.
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- Kassamakova, L, et al.
(författare)
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Al/Si ohmic contacts to p-type 4H-SiC for power devices
- 2000
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Ingår i: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 338-3, s. 1009-1012
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Tidskriftsartikel (refereegranskat)abstract
- The formation of Al/Si/p-4H SiC ohmic contacts at temperatures as low as 750 degreesC is reported in this paper. The dependence of electrical properties and contact morphology have been investigated as a function of the annealing regime in the interval 600-700 degreesC. The lowest contact resistivity of 3.8x10(-5) Omega .cm(2) was obtained at 700 degreesC annealing, however the most reproducible results were in the low 10(-4) Omega .cm(2) range. It has been established that the predominate current transport mechanism in the Al/Si/SiC contacts is thermionic-field emission. Atomic force microscopy showed that the addition of Si to the contact layer improves its morphology, and the pitting of annealed Al is not observed. The contacts developed are stable during ageing at 500 degreesC and at operating temperatures up to 450 degreesC. After the contacts testing with current density of 10(3) A/cm(2) at temperatures up to 450 degreesC, their contact resistivity decreases slightly.
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- Konstantinov, A., et al.
(författare)
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Operation of Silicon Carbide BJTs Free from Bipolar Degradation
- 2010
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Ingår i: SILICON CARBIDE AND RELATED MATERIALS 2009, PTS 1 AND 2. ; , s. 1057-1060
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Konferensbidrag (refereegranskat)abstract
- The mechanisms of bipolar degradation in silicon carbide BJTs are investigated and identified. Bipolar degradation occurs as result of stacking fault (SF) growth within the low-doped collector region. A stacking fault blocks vertical current transport through the collector, driving the defective region into saturation. This results in considerable drop of emitter current gain if the BJT is run at a reasonably low collector-emitter bias. The base region does not play any significant role in bipolar degradation. Long-term stress tests have shown full stability of large-area high-power BJTs under minority carrier injection conditions provided the devices are fabricated using low Basal Plane Dislocation (BPD) material. However, an approximately 20% current gain compression is observed for the first 30-60 hours of burn-in under common emitter operation, which is related to instability of surface recombination in the passive base region.
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- Svedberg, Gudrun, 1962-
(författare)
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Entreprenörskapets avtryck i klassrummets praxis : om villkor och lärande i gymnasieskolans entreprenörskapsprojekt
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Entrepreneurship has been entered on a supranational political agenda, in the EU and the OECD, and been emphatically described as a fundamental skill and a concern for schools and education. The agenda is reflected to a varying extent at the national and regional political levels. My aim is to describe, analyze and gain knowledge of what entrepreneurship in the Swedish upper secondary schools imply in practice, against the background of a local context. In particular, the conditions for learning. My approach is ethnographically inspired and this multiple case study is limited to two upper secondary school programmes. Data has been collected through observations, video recordings, informal conversations with pupils and teachers and formal conversations with headmasters. The material is analyzed in terms of three socioculturally inspiring foci. By means of a cultural-institutional focus, the stability and changeability of the programmes were elucidated. The previous institutional frameworks have been partially questioned by the teachers in the field, which has resulted in the following: In one of the upper secondary schools a new locally adapted programme has been composed, and courses and subjects have been integrated in a new way in the other school’s existing programme. The changes in the upper secondary programmes are to a great extent an example of a meeting between top-down and bottom-up initiatives. The changes of the institutional frameworks are connected to a discursive shift of the responsibility for pupils’ learning and education from teachers to pupils and also to teacher’s ambition to adapt interest- and experience-related teaching. In a situated focus, both programmes were identified as communities of practice with a joint enterprise, mutual engagement and a shared repertoire. These three dimensions were useful for examining specific aspects of the teaching. There has above all been an altered balance between reification and participation in the teaching as well as boundary crossing both outside the community of practice and within the community. Different conditions for learning were identified through an interpersonal focus. Both collaborative learning and cooperative learning were useful, but not sufficient concepts for describing the various forms of team learning. The conditions of cooperation and the pupils’ communication patterns revealed yet another form of team learning, which I call comparative learning. If the risk of everyday concepts getting the upper hand and trivialization can be avoided in team learning, there is in all these learning processes a potential for the pupils being able to develop strategies for handling complex tasks, taking initiatives and responsibility, cooperating and learning from one another in various different ways. In this way entrepreneurship has had an impact on the practice of the classrooms.
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