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- Heyman, A., et al.
(author)
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Band structure and spin polarization for a one-dimensional array of quantum point contacts
- 2004
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In: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 15:1, s. 143-148
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Journal article (peer-reviewed)abstract
- We have numerically studied the band structure and the spin polarization effect in a periodic one-dimensional array of quantum point contacts (QPCs) formed in a two-dimensional electron gas in a plane-layered semiconductor system. In this study we used a self-consistent model developed within the framework of the Kohn-Sham local spin-density formalism. We have found that the band structure contains a mixture of flat and dispersed bands, and the role of transverse modes in the formation of such a band structure has been clearly demonstrated. We have also shown that spin polarization occurs mainly in the regions occupied by the QPCs and that it is qualitatively similar to the spin polarization in a single QPC.
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- Bersellini Farinotti, Alex, et al.
(author)
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Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
- 2019
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
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- Blomdin, Robin, et al.
(author)
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Evaluating the timing of former glacier expansions in the Tian Shan : A key step towards robust spatial correlations
- 2016
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 153, s. 78-96
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Journal article (peer-reviewed)abstract
- The timing of past glaciation across the Tian Shan provides a proxy for past climate change in this critical area. Correlating glacial stages across the region is difficult but cosmogenic exposure ages have considerable potential. A drawback is the large observed scatter in Be-10 surface exposure data. To quantify the robustness of the dating, we compile, recalculate, and perform statistical analyses on sets of 10Be surface exposure ages from 25 moraines, consisting of 114 new and previously published ages. We assess boulder age scatter by dividing boulder groups into quality classes and rejecting boulder groups of poor quality. This allows us to distinguish and correlate robustly dated glacier limits, resulting in a more conservative chronology than advanced in previous publications. Our analysis shows that only one regional glacial stage can be reliably correlated across the Tian Shan, with glacier expansions occurring between 15 and 281 a during marine oxygen isotope stage (MIS) 2. However, there are examples of older more extensive indicators of glacial stages between MIS 3 and MIS 6. Paleoglacier extent during MIS 2 was mainly restricted to valley glaciation. Local deviations occur: in the central Kyrgyz Tian Shan paleoglaciers were more extensive and we propose that the topographic context explains this pattern. Correlation between glacial stages prior to late MIS 2 is less reliable, because of the low number of samples and/or the poor resolution of the dating. With the current resolution and spatial coverage of robustly-dated glacier limits we advise that paleoclimatic implications for the Tian Shan glacial chronology beyond MIS 2 are speculative and that continued work toward robust glacial chronologies is needed to resolve questions regarding drivers of past glaciation in the Tian Shan and Central Asia.
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| 12. |
- Blomdin, Robin, et al.
(author)
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Timing and dynamics of glaciation in the Ikh Turgen Mountains, Altai region, High Asia
- 2018
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In: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 47, s. 54-71
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Journal article (peer-reviewed)abstract
- Spanning the northern sector of High Asia, the Altai region contains a rich landform record of glaciation. We report the extent, chronologies, and dynamics of two paleoglaciers on opposite flanks of the Ikh Turgen mountains (In Russian: Chikhacheva Range), straddling the border between Russia and Mongolia, using a combination of remote sensing-based glacial geomorphological mapping, 10Be surface exposure dating, and geomorphometric analysis. On the eastern side (Mongolia), the Turgen-Asgat paleoglacier, with its potential for developing a large accumulation area (∼257 km2), expanded 40 km down valley, and mean ages from a latero-frontal moraine indicate deglaciation during marine oxygen isotope stage (MIS) 3 (45.1 ± 1.8 ka, n = 4) and MIS 2 (22.8 ± 3.3 ka, n = 5). These minimum age constraints are consistent with other 10Be glacial chronologies and paleoclimate records from the region, which indicates glacier culmination during cold and wet conditions coinciding with MIS 3 (piedmont-style glaciation; inferred for a few sites across the region) and glacier culmination during cold and dry conditions coinciding with MIS 2 (mainly valley-style glaciation; inferred from several sites across the region). On the western side (Russia), the Boguty paleoglacier had a smaller accumulation area (∼222 km2), and advanced 30 km down valley across a low gradient forefield. Surface exposure ages from two moraine complexes on this side of the mountains exhibit wide scatter (∼14–53 ka, n = 8), making paleoclimate inferences and comparison to other proxies difficult. Ice surface profile reconstructions imply that the two paleoglaciers likely shared an ice divide. © 2018 Elsevier B.V.
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- Hall, CL, et al.
(author)
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Investigating a therapist-guided, parent-assisted remote digital behavioural intervention for tics in children and adolescents-'Online Remote Behavioural Intervention for Tics' (ORBIT) trial: protocol of an internal pilot study and single-blind randomised controlled trial
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e027583-
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Journal article (peer-reviewed)abstract
- Tourette syndrome and chronic tic disorder are common, disabling childhood-onset conditions. Guidelines recommend that behavioural therapy should be offered as first-line treatment for children with tics. However, there are very few trained behaviour therapists for tics and many patients cannot access appropriate care. This trial investigates whether an internet-delivered intervention for tics can reduce severity of symptoms.Methods and analysisThis parallel-group, single-blind, randomised controlled superiority trial with an internal pilot will recruit children and young people (aged 9–17 years) with tic disorders. Participants will be randomised to receive 10 weeks of either online, remotely delivered, therapist-supported exposure response prevention behavioural therapy for tics, or online, remotely delivered, therapist-supported education about tics and co-occurring conditions. Participants will be followed up mid-treatment, and 3, 6, 12 and 18 months post randomisation.The primary outcome is reduction in tic severity as measured on the Yale Global Tic Severity Scale total tic severity score. Secondary outcomes include a cost-effectiveness analysis and estimate of the longer-term impact on patient outcomes and healthcare services. An integrated process evaluation will analyse quantitative and qualitative data in order to fully explore the implementation of the intervention and identify barriers and facilitators to implementation. The trial is funded by the National Institute of Health Research (NIHR), Health Technology Assessment (16/19/02).Ethics and disseminationThe findings from the study will inform clinicians, healthcare providers and policy makers about the clinical and cost-effectiveness of an internet delivered treatment for children and young people with tics. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval from North West Greater Manchester Research Ethics Committee (ref.: 18/NW/0079).Trial registration numbersISRCTN70758207andNCT03483493; Pre-results.
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| 18. |
- Hall, CL, et al.
(author)
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The COVID-19 pandemic and its impact on tic symptoms in children and young people: a prospective cohort study
- 2023
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In: Child psychiatry and human development. - : Springer Science and Business Media LLC. - 1573-3327 .- 0009-398X. ; 54:6, s. 1499-1509
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Journal article (peer-reviewed)abstract
- To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9–17 years) randomised to the control arm of the “ORBIT-Trial” (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months’ post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms.
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| 19. |
- Hjelm, Fredrik, et al.
(author)
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A novel B cell-mediated transport of IgE-immune complexes to the follicle of the spleen.
- 2008
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 180:10, s. 6604-6610
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Journal article (peer-reviewed)abstract
- Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4(+) T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcgammaRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4(+) T cells by CD23(+) B cells and that IgG2a/Ag is presented by FcgammaR(+) dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23(high)) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4(+) T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4(+) T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.
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- Ivanov Öfverholm, I., et al.
(author)
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Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia
- 2020
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In: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:3, s. 604-613
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Journal article (peer-reviewed)abstract
- Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21. RNA sequencing revealed that only half of the genes in the minimal region of amplification (20/45) were differentially expressed in iAMP21. Among them were the top overexpressed genes (p < 0.001) in iAMP21 vs. BCP ALL without iAMP21 and three candidate genes could be identified, the tyrosine kinase gene DYRK1A and chromatin remodeling genes CHAF1B and SON. While overexpression of DYRK1A and CHAF1B is associated with poor prognosis in malignant diseases including myeloid leukemia, this is the first study to show significant correlation with iAMP21-positive ALL.
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