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- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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- Rachmeler, L. A., et al.
(författare)
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Quiet Sun Center to Limb Variation of the Linear Polarization Observed by CLASP2 Across the Mg ıı h and k Lines
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 936:1
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Tidskriftsartikel (refereegranskat)abstract
- The CLASP2 (Chromospheric LAyer Spectro-Polarimeter 2) sounding rocket mission was launched on 2019 April 11. CLASP2 measured the four Stokes parameters of the Mg ıı h and k spectral region around 2800 Å along a 200'' slit at three locations on the solar disk, achieving the first spatially and spectrally resolved observations of the solar polarization in this near-ultraviolet region. The focus of the work presented here is the center-to-limb variation of the linear polarization across these resonance lines, which is produced by the scattering of anisotropic radiation in the solar atmosphere. The linear polarization signals of the Mg ıı h and k lines are sensitive to the magnetic field from the low to the upper chromosphere through the Hanle and magneto-optical effects. We compare the observations to theoretical predictions from radiative transfer calculations in unmagnetized semiempirical models, arguing that magnetic fields and horizontal inhomogeneities are needed to explain the observed polarization signals and spatial variations. This comparison is an important step in both validating and refining our understanding of the physical origin of these polarization signatures, and also in paving the way toward future space telescopes for probing the magnetic fields of the solar upper atmosphere via ultraviolet spectropolarimetry.
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- Bethge, WA, et al.
(författare)
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Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients
- 2022
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 57:3, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.
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- Dohlus, M., et al.
(författare)
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Application of Accelerators and Storage Rings
- 2020
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Ingår i: Particle Physics Reference Library : Volume 3: Accelerators and Colliders - Volume 3: Accelerators and Colliders. - Cham : Springer International Publishing. - 9783030342456 - 9783030342449 ; 3, s. 661-795
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Bokkapitel (refereegranskat)abstract
- It is well known from Maxwell theory that electromagnetic radiation is emitted whenever electric charges are accelerated in free space. This radiation assumes quite extraordinary properties whenever the charged particles move at ultrarelativistic speed: The radiation becomes very powerful and tightly collimated in space, and it may easily cover a rather wide spectrum ranging from the THz into the hard X-ray regime. When generation of such radiation is intended rather than being a side effect, the charged particles are normally electrons, thus kinetic energies are then typically in the multi-MeV range.
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- Schmit, D., et al.
(författare)
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Comparison of Solar Fine Structure Observed Simultaneously in Ly alpha and MgII h
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 847:2
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Tidskriftsartikel (refereegranskat)abstract
- The Chromospheric Lyman Alpha Spectropolarimeter (CLASP) observed the Sun in H I Ly alpha during a suborbital rocket flight on 2015 September 3. The Interface Region Imaging Telescope (IRIS) coordinated with the CLASP observations and recorded nearly simultaneous and co-spatial observations in the Mg II h and k lines. The Mg II h and Lya lines are important transitions, energetically and diagnostically, in the chromosphere. The canonical solar atmosphere model predicts that these lines form in close proximity to each other and so we expect that the line profiles will exhibit similar variability. In this analysis, we present these coordinated observations and discuss how the two profiles compare over a region of quiet Sun at viewing angles that approach the limb. In addition to the observations, we synthesize both line profiles using a 3D radiation-MHD simulation. In the observations, we find that the peak width and the peak intensities are well correlated between the lines. For the simulation, we do not find the same relationship. We have attempted to mitigate the instrumental differences between IRIS and CLASP and to reproduce the instrumental factors in the synthetic profiles. The model indicates that formation heights of the lines differ in a somewhat regular fashion related to magnetic geometry. This variation explains to some degree the lack of correlation, observed and synthesized, between Mg II and Lya. Our analysis will aid in the definition of future observatories that aim to link dynamics in the chromosphere and transition region.
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- Bethge, O., et al.
(författare)
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Effective reduction of trap density at the Y2O3/Ge interface by rigorous high-temperature oxygen annealing
- 2014
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 116:21, s. 214111-
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Tidskriftsartikel (refereegranskat)abstract
- The impact of thermal post deposition annealing in oxygen at different temperatures on the Ge/Y2O3 interface is investigated using metal oxide semiconductor capacitors, where the yttrium oxide was grown by atomic layer deposition from tris(methylcyclopentadienyl) yttrium and H2O precursors on n-type (100)-Ge substrates. By performing in-situ X-ray photoelectron spectroscopy, the growth of GeO during the first cycles of ALD was proven and interface trap densities just below 1 x 10(11) eV(-1) cm(-2) were achieved by oxygen annealing at high temperatures (550 degrees C-600 degrees C). The good interface quality is most likely driven by the growth of interfacial GeO2 and thermally stabilizing yttrium germanate.
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- Ishikawa, Ryohko, et al.
(författare)
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Mapping solar magnetic fields from the photosphere to the base of the corona
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Routine ultraviolet imaging of the Sun’s upper atmosphere shows the spectacular manifestation of solar activity; yet, we remain blind to its main driver, the magnetic field. Here, we report unprecedented spectropolarimetric observations of an active region plage and its surrounding enhanced network, showing circular polarization in ultraviolet (Mg ii h & k and Mn i) and visible (Fe i) lines. We infer the longitudinal magnetic field from the photosphere to the very upper chromosphere. At the top of the plage chromosphere, the field strengths reach more than 300 G, strongly correlated with the Mg ii k line core intensity and the electron pressure. This unique mapping shows how the magnetic field couples the different atmospheric layers and reveals the magnetic origin of the heating in the plage chromosphere.
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- Song, Donguk, et al.
(författare)
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Polarization Accuracy Verification of the Chromospheric LAyer SpectroPolarimeter
- 2022
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Ingår i: Solar Physics. - : Springer Science and Business Media LLC. - 0038-0938 .- 1573-093X. ; 297:10
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Tidskriftsartikel (refereegranskat)abstract
- We have developed an advanced UV spectropolarimeter called Chromospheric LAyer SpectroPolarimeter (CLASP2), aimed at achieving very high accuracy measurements (<0.1% at 3σ) of the linear (Q/I and U/I) and circular (V/I) polarizations of the Mg II h and k lines (280 nm). CLASP2 was launched on board a NASA sounding rocket on April 11, 2019. It successfully detected the full Stokes vector in an active-region plage and in the quiet Sun near the limb across the Mg II h and k lines for the first time. To verify the polarization characteristics of CLASP2, the response matrix is estimated by combining the results obtained from the preflight calibration on the ground, with the results of the inflight calibration acquired at the solar-disk center. We find that the response matrix of CLASP2 in the Mg II h and k lines is notably close to an ideal response matrix, i.e., the scale factor and the crosstalk terms are close to 1 and 0, respectively. Moreover, the uncertainty of each Stokes parameter estimated by the repeatability of the measurements is verified to be within the required tolerance. Based on our investigation, we conclude that CLASP2 achieves 0.1% polarization accuracy at a 3σ3σ level.
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15. |
- Wirths, Oliver, et al.
(författare)
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Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer's disease cases
- 2010
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 117:1, s. 85-96
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Tidskriftsartikel (refereegranskat)abstract
- The presence of Abeta(pE3) (N-terminal truncated Abeta starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Abeta peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, Abeta(pE3) has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Abeta. We have recently shown that intraneuronal accumulation of Abeta(pE3) peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Abeta(pE3), we have generated two novel monoclonal antibodies which were characterized as highly specific for Abeta(pE3) peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for Abeta(pE3) were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in Abeta(pE3) plaque load with increasing age, while the density for Abeta(1-x ) plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Abeta are N-truncated as disease progresses, and that, Abeta(pE3) positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.
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